222 results on '"Serotonina"'
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2. DESCRIPTION OF GENETIC FACTORS ASSOCIATED WITH SUICIDAL BEHAVIOR AND SUICIDE: A TOPICAL REVIEW.
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Constanza-Cañón, Sandra, García-Restrepo, Natalia, María Aluma-Betancourt, Lina, Botero-Peláez, Daniela, Devia-Cabrera, Mariana, Rojas-Vargas, Elisa, Manuela Sánchez-Pinto, Laura, Piedrahita Muñoz, Santiago, Hurtado-Salazar, Verónica, and Manuela Rodríguez-Gutiérrez, María
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SUICIDE risk factors ,SELF-injurious behavior ,GENETIC markers ,MENTAL illness ,CELLULAR signal transduction ,SUICIDAL behavior ,GENETIC variation ,MEDLINE ,SUICIDE ,NORADRENALINE ,HUMAN genome ,SEROTONIN ,DOPAMINE ,ONLINE information services ,MENTAL depression ,GENOTYPES ,NERVE growth factor ,PSYCHOSOCIAL factors - Abstract
Copyright of Revista de la Facultad de Medicina Humana is the property of Instituto de Investigaciones en Ciencias Biomedicas de la Universidad Ricardo Palma and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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3. Hipoprolactinemia y disfunción sexual masculina
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Jeiver Aldubar Contreras Romero, Kevin Guillermo Castro Gomez, Maria Paula Morales Ortigoza, Ana María Mora-Vargas, Sandra Liliana Cabezas-Martínez, and Harold Felipe Saavedra-López
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prolactina ,disfunción sexual ,deficiencia de prolactina ,disfunción eréctil ,serotonina ,salud del hombre ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Contexto: la prolactina es una hormona con múltiples funciones neuroendocrinas, el rol más estudiado es en la función reproductiva, aún no es claro por qué su deficiencia causa disfunción sexual, sin embargo, se ha relacionado con la función gonadal. Objetivo: presentar la información actual sobre la estructura y aspectos moleculares de la PRL, el papel de la serotonina, y la relación fisiopatológica de la hipoprolactinemia y la disfunción sexual masculina. Metodología: revisión de la literatura en las bases de datos PubMed, Lilacs, Embase, Scopus, Scielo, Google Académico y literatura gris utilizando vocabulario controlado DE MeSH, DeCS y Emtree. Resultados: existe poca evidencia acerca de la hipoprolactinemia y disfunción sexual, sin embargo, parecen ser manifestaciones de una alteración serotoninérgica y sus efectos metabólicos, siendo importante conocer los aspectos básicos, fisiopatológicos y clínicos que convierten a esta entidad en una de las causas asociadas a este síndrome. Conclusiones: la hipoprolactinemia es uno de los factores de menor protagonismo por la escasa información disponible con respecto a su rol en la disfunción sexual, esto motiva a desarrollar investigaciones que profundicen el entendimiento de la enfermedad.
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- 2024
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4. Sąsiad sąsiadowi wilkiem. Motyw sąsiedztwa w prozie Michela Houellebecqa
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Kinga Strzelecka-Pilch
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michel houellebecq ,uległość ,serotonina ,unicestwianie ,sąsiedztwo ,Language and Literature - Abstract
Inność, obcość, wymóg sąsiadowania ze wszystkim, co nie moje – to główne tematy powieści Michela Houellebecqa. Główny bohater wykreowany przez francuskiego pisarza jest nihilistą, który nie potrafi utożsamić się z niczym, nawet z samym sobą, a każdy kontakt z innością budzi jego lęk, sprzeciw i agresję. Przykre i nieznośne sąsiedztwo innych pozwala mu jednak definiować siebie: w Uległości definiuje się w kontrze do tradycji muzułmańskiej, w Serotoninie pogardza Holendrami i własną azjatycką narzeczoną, w Unicestwianiu jako mięsożerca prowadzi walki o zawartość domowej lodówki. Sąsiedztwo wzmaga u niego poczucie samotności, a obserwowanie innych kultur, narodów, tradycji, przyzwyczajeń prowadzi do jednej, gorzkiej refleksji – nie należę nigdzie, dlatego jestem zupełnie sam. Jakim sąsiadem może być mizantrop totalny? I dlaczego Houellebecq w epoce otwartości, tolerancji, pochwały piękna i samodoskonalenia się wybrał właśnie ten rodzaj autokreacji?
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- 2023
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5. Actualización sobre la comorbilidad migraña-depresión
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Gustavo A Díaz-Silva, Andrés F Alzate-Arbeláez, María Isabel Valencia-Osorio, Miguel Orozco-Vanegas, and Pablo Domínguez-Ruiz
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migraña ,depresión ,comorbilidad ,serotonina ,salud mental ,dolor crónico ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Introducción: la migraña y el trastorno depresivo son patologías altamente prevalentes e incapacitantes, las cuales presentan relaciones bidireccionales de comorbilidad. En la literatura se han descrito factores de riesgo y mecanismos fisiopatológicos comunes para ambas enfermedades, así como asociaciones entre estas y su presentación clínica. Métodos: el presente texto es una revisión narrativa de la literatura. La búsqueda del material bibliográfico se hizo mediante distintas bases de datos especializadas en el área de la salud. Resultados: algunos factores de riesgo están asociados con ambas patologías, y ambas comparten factores patogénicos, incluidos cambios funcionales, estructurales, genéticos, epigenéticos y hormonales, entre otros. Varios de los tratamientos preventivos que han demostrado eficacia en el tratamiento de la migraña son medicamentos o medidas con efecto antidepresivo. Discusión: si se consideran las asociaciones y los factores comunes descritos en la literatura, se hace evidente que en el enfoque de pacientes diagnosticados con alguna de estas patologías es necesario tener en cuenta una posible comorbilidad entre migraña y depresión. Conclusión: es importante promover el tamizaje de estas dos condiciones en pacientes diagnosticados con alguna de ellas, pues esto puede tener implicaciones terapéuticas e impacto en la calidad de vida.
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- 2023
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6. Confirmation of the presence of serotonergic cells in the fetal cerebral cortex in cultures and in situ.
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Boyzo-Montes de Oca, Alfonso, Manjarrez-Gutiérrez, Gabriel, and Hernández-Rodríguez, Jorge
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- 2023
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7. Effects of tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective serotonin-norepinephrine reuptake inhibitors on the ocular surface.
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Ismayilov, Ayna Sariyeva and Celikel, Guler
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SEROTONIN uptake inhibitors ,ANTIDEPRESSANTS ,TRICYCLIC antidepressants ,BECK Anxiety Inventory ,BECK Depression Inventory ,DRY eye syndromes ,SEROTONIN syndrome - Abstract
Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2023
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8. Gastroesophageal tube of the Iguana iguana (Iguanidae): histological description, histochemical and immunohistochemical analysis of 5-HT and SS cells.
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Serra-Campos, A. O., Abreu-Junior, A. N. G., Nascimento, A. A., Abidu-Figueiredo, M., Lima, M. S. C. S., and Machado-Santos, C.
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ENTEROENDOCRINE cells ,IMMUNOHISTOCHEMISTRY ,IGUANAS ,IMMUNOHISTOCHEMISTRY techniques ,HISTOLOGICAL techniques ,STAINS & staining (Microscopy) ,ENDOCRINE system ,ISLANDS of Langerhans - Abstract
Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2023
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9. When drug-centred psychopharmacology meets person-centred psychopharmacotherapy - antidepressants.
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Murawiec, Sławomir
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PSYCHOPHARMACOLOGY , *ANTIDEPRESSANTS , *DRUG therapy , *SEROTONIN uptake inhibitors - Abstract
A vibrant discussion on the monoamine theory of depression and the use of serotonergic modulators in the treatment of this disorder was triggered by a systematic review published by Moncrieff et al. in "Molecular Psychiatry" in 2022. Many experts considered this work as referring to a hypothesis that now is only of historical significance. Another publication, co-authored by Moncrieff, proposed a useful approach to both action and clinical use of psychopharmacotherapy. The drug-centred model postulates that psychoactive agents are substances that affect symptoms indirectly, by exerting specific effects on physiological phenomena underlying mental, emotional and behavioural processes. When planning therapeutic strategy, it should be assessed whether the expected effects of a given medication on mental function and behaviour may prove beneficial in a particular life situation of the person being treated. Therefore, pharmacotherapy can be considered in terms of its impact on mental functions, which may turn out positive (not only for depression, but also for anxiety and other disorders), rather than targeting a specific abnormality. The paper presents different approaches within this framework, including a model based on creative person-centred narrative psychopharmacotherapy (CP-CNP) described by Jakovljević. Combining drug-centred and person-centred psychopharmacotherapy may be the basis for understanding the pharmacological treatment of mental disorders. In the context of the controversy aroused by Moncrieff et al., it can be pointed out that agents known to modulate serotonin transmission modify certain serotonin-mediated mental functions, which may aid the treatment of depression and many other conditions. Therefore, it is not a mechanically understood antidepressant effect. Serotonin modulators are useful in the treatment of depression, as evidenced by both scientific research and the experiences of millions of patients. However, these drugs have a complex, multistage action, which needs to be considered to avoid misunderstandings and oversimplifications. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Serotonin transporter gene methylation and emotional regulation in preschool children born preterm: A longitudinal evaluation of the role of negative emotionality in infancy.
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Mascheroni, Eleonora, Schiavolin, Paola, Mariani Wigley, Isabella Lucia Chiara, Giorda, Roberto, Pozzoli, Uberto, Morandi, Francesco, Fontana, Camilla, Mosca, Fabio, Fumagalli, Monica, and Montirosso, Rosario
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SEROTONIN transporters , *PRESCHOOL children , *EMOTION regulation , *METHYLATION , *DNA methylation , *SEROTONIN receptors , *WEIGHT in infancy - Abstract
The aim of the study was to assess the contribution of negative emotionality at 3 months (T1) and serotonin transporter gene (SLC6A4) DNA methylation at 4.5 years of age (T2) to emotion regulation in pre‐schoolers born very preterm and full‐term. Forty one children (n = 21 born very preterm, n = 20 born full‐term) participated in the study. Fretful behavior was assessed at T1 in response to the Face‐to‐FaceStill‐Face (FFSF) paradigm. At T2, SLC6A4 DNA methylation was analyzed and emotion regulation was assessed using an observational procedure (i.e., the Pre‐schooler Regulation of Emotional Stress, PRES). The very preterm group displayed higher emotion dysregulation during the PRES Reactivity phase than the full‐term group. Higher levels of fretful behavior at 3 months were associated with greater emotional distress only for very preterm children with higher methylation at T2. No significant associations emerged in the full‐term group. Despite current findings cannot be generalized owing to the relatively small sample size, this work provides preliminary longitudinal evidence about the link between negative emotionality during infancy, stress‐linked epigenetic status at 4.5 years and emotion dysregulation in preschoolers born preterm. [ABSTRACT FROM AUTHOR]
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- 2022
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11. La hipocalcemia en la vaca lechera. Revisión
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Carlos Fernando Arechiga-Flores, Zimri Cortés-Vidauri, Pedro Hernández-Briano, Renato Raúl Lozano-Domínguez, Marco Antonio Lòpez-Carlos, Ulises Macias-Cruz, and Leonel Avendaño-Reyes
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Hipocalcemia ,Vaca lechera ,Homeostasis ,Calcio ,Serotonina ,Metritis ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 - Abstract
Los niveles de calcio (Ca) disminuyen en sangre y citosol al momento del parto, alterando la transmisión del impulso nervioso, la contracción muscular y la actividad de las células inmunes. En el sistema nervioso el Ca participa en la conducción de estímulos. En el sistema muscular disminuye la contracción causando alteraciones en músculo liso, útero y glándula mamaria. En el útero hay retención y almacenamiento de fluidos y desechos uterinos, con complicaciones bacterianas. En el sistema inmune, es importante la función de los neutrófilos y se manifiesta con una disminución de células dedicadas a la fagocitosis predisponiendo a mastitis y metritis. En la hipocalcemia bovina se distinguen dos presentaciones: clínica y subclínica. En la clínica (valores de Ca inferiores a 5.5 mg/dl) se altera la homeostasis con pérdida de apetito, decúbito y letargo. La hipocalcemia subclínica es más común (Ca entre 8.0 y 5.5 mg/dl), y no se altera la homeostasis, pero si se reduce la contracción muscular y la función inmune. El tratamiento se basa en la aplicación de calcio vía oral en vacas de pie, y vía endovenosa en las vacas postradas. La prevención depende de la inclusión de raciones que contengan sales aniónicas con lo cual se favorece el estímulo de mantener los niveles de Ca sanguíneos para controlar el nivel de cationes y aniones. Además, se puede administrar Ca vía oral. La homeostasis de calcio en la lactancia es regulada por la hormona serotonina, que estimula a la hormona paratiroidea y la reabsorción ósea en los osteoclastos.
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- 2022
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12. The role of serotoninergic system in psychostimulant effects.
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Taracha, Ewa
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SEROTONINERGIC mechanisms , *DOPAMINE agents , *COCAINE , *RESPONSE inhibition , *PHARMACOLOGY - Abstract
Purpose: This article discusses the modulatory effects of the serotonergic system on the behavioral and neurochemical effects exerted by psychostimulants, mainly cocaine. Views: The mesocorticolimbic dopaminergic system plays an important role in the rewarding effects of psychostimulants and the long-lasting neuroadaptive changes underlying the development of addiction. Dopaminergic brain regions such as the ventral tegmental area (VTA) and substantia nigra (SN) and their projection fields (prefrontal cortex - PFC, nucleus accumbens - Acb, dorsal striatum) are innervated by serotonergic neurons that can modulate this system. Pharmacological manipulation of the activity of the serotonergic system in rats has shown that lowering or elevating its activity increases and decreases, respectively, most behavioral responses to cocaine. Studies on the role of serotonin receptors have shown that the serotonin 5-HT1B receptor agonists administered to the Acb during self-administration increase the reinforcing effects of cocaine, whereas when administered during abstinence they decrease cocaine seeking. Distinct populations of 5-HT2AR and 5-HT2CR in the PFC, Acb, and VTA differentially affect the output of the mesocorticolimbic dopaminergic pathway. 5-HT2B receptors exert independent control over the activity of the three ascending dopamine (DA) pathways through specific tonic excitatory and inhibitory control of DA efflux from the Acb and PFC and do not affect striatal activity. Conclusions: The serotonergic system exerts modulatory effects on the behavioral and neurochemical effects of psychostimulants. The pharmacological manipulation of serotonergic system activity makes it possible to attenuate the effects of psychostimulants, which gives hope for the development of effective pharmacotherapy. Currently, the main obstacle to this is the excessive side effects shown by potential drugs. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Hiperprolactinemia en psicosis tempranas: ¿secundaria a estrés o a una regulación alterada de la secreción de prolactina? .
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J. Labad, A. Armario, R. Nadal, J. Ortiz, R. Andero, J. Giraldo, R. Coronas, J.A. Monreal, and D.J. Palao
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Prolactina ,Psicosis ,Estrés ,Dopamina ,Serotonina ,Psychology ,BF1-990 ,Psychiatry ,RC435-571 - Abstract
En la última década estudios previos han demostrado un aumento de las cifras de prolactina en pacientes con un primer episodio psicótico libres de tratamiento respecto a controles sanos. Aunque no existen mecanismos fisiopatológicos claros, existe la posibilidad de que se trate de una alteración secundaria al contexto estresante del debut psicótico. Alternativamente, los pacientes con un trastorno psicótico podrían sufrir una regulación anómala de la secreción de prolactina con un exceso de factores estimuladores o un defecto de los factores inhibitorios. En la presente revisión narrativa se comentan diferentes posibles mecanismos fisiopatológicos implicados incluyendo el papel del estrés y la regulación de la secreción de prolactina en la vía tuberoinfundibular, que puede evaluarse clínicamente con pruebas funcionales endocrinológicas. Este conocimiento ofrece una oportunidad de investigar las causas de estas alteraciones y dilucidar los mecanismos implicados en la hiperprolactinemia en fases tempranas de psicosis.
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- 2021
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14. Colapso de dos endocanabinoides (AEA y PEA) en sangre en los grandes repetidores: hallazgos disruptivos en un estudio piloto
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Hilario Blasco-Fontecilla, Javier Herranz-Herrer, Teresa Ponte-López, Elena Gil-Benito, Belén Sanz, Eva Suárez, María Rodrigo-Yanguas, María Gil-Ligero, Silvia Rosado-García, Silvia Ortega-Gutiérrez, and Antonio Sánchez-López
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Intento suicida ,Serotonina ,Beta-endorfina ,Endocannabinoides ,Psychology ,BF1-990 ,Psychiatry ,RC435-571 - Published
- 2021
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15. A new theory of depression based on the serotonin/kynurenine relationship and the hypothalamicpituitary- adrenal axis
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Leslie Alejandra Ramírez, Elsy Arlene Pérez-Padilla, Francisco García-Oscos, Humberto Salgado, Marco Atzori, and Juan Carlos Pineda
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depresión ,sistema nervioso ,sistema inmunológico ,serotonina ,inmunidad innata, interleucina-1beta ,interleucina-6 ,interleucina-10 ,interferón gamma ,neuroglia ,sistema hipotálamohipófiso- suprarrenal ,Medicine ,Arctic medicine. Tropical medicine ,RC955-962 - Abstract
The serotonergic and immunological hypothesis of depression proposes that certain types of excessive stress distort the relationship between the activities of the innate immune and central nervous systems, so that the stress caused by an infection, or excessive psychological stress, activate toll-like receptors such as the TLR-4, the transcription factor NF-kB, the inflammasome NLRP3, as well as the secretion of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and other factors of the innate immune response, causing first, the general symptoms of the disease which appear with any infection, but also those characteristic of depressive illness such as dysphoria and anhedonia. The evidence indicates that, if the stimulus persists or recurs within 24 hours, the indole-2, 3-dioxygenase enzyme (IDO) of the kynurenine metabolic pathway, which increases the synthesis of quinolinic acid, is activated with an associated reduction of serotonin synthesis. Quinolinic acid activates NMDA receptors in the central nervous system and stimulates the secretion of interleukins IL-6 and 1L-1β, among others, promoting hyper-activity of the HPA axis and reinforcing a bias of the tryptophan metabolism to produce quinolinic acid, and interleukins by the innate immune system, further reducing the synthesis of serotonin and consolidating the depressive process. We discuss the evidence showing that this process can be initiated by either interleukin stimulated by an infection or some vaccines or excessive psychological stress that activates the HPA axis together with said innate immune response, causing a process of aseptic inflammation in the central nervous system.
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- 2018
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16. Association of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci.
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Delia Genis-Mendoza, Alma, Nicolini, Humberto, Manrique, Viana, López-Canovas, Lilia, Cabrera-Mendoza, Brenda, Bobes, María Antonieta, Lanzagorta, Nuria, and Santana, Daniel
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ANTIBODY titer , *GENETIC polymorphisms , *NEUROBEHAVIORAL disorders , *STREPTOCOCCUS , *AUTOANTIBODIES , *OBSESSIVE-compulsive disorder , *SEROTONIN transporters , *AUTOIMMUNE diseases - Abstract
Introduction. It has been hypothesized that pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) etiology results from an abnormal immune response to streptococcal infection. There is evidence that the serotonergic system is involved in both obsessive-compulsive disorder (OCD) physiopathology and immunological processes. In the 5' promoter region of 5-HTT, gene encoding for the serotonin transporter we can find the 5-HTTLPR polymorphism that has been associated with OCD. Being PANDAS a disorder with OCD symptoms and likely immune abnormalities, 5-HTT polymorphisms may be particularly relevant for this disorder. Objective. This study aimed to test the association between the 5-HT genotypes and the presence of serum antibodies in patients with PANDAS. Method. We compared the genotype frequencies and serum anti-streptococcal, anti-neural, and anti-enolase antibodies titers between 56 patients with PANDAS and 20 healthy controls from Mexico and Cuba. Results. Antibody titers were higher (anti-enolase, anti-streptococcal) in PANDAS patients compared to healthy controls. No differences in anti-neural antibody levels between both groups were detected. The anti-enolase and anti-neural antibody titer increased according to the polymorphism of the PANDAS patients as follows: LL >SL >SS. Discussion and conclusion. This is the first study evaluating the association between the 5-HTTLPR genotypes and antibody titers in PANDAS patients. Associations between polymorphisms in serotonergic genes and immune response could provide valuable information about the interaction between both systems. Our results suggest an association between the S allele and elevated antibody levels in PANDAS patients. [ABSTRACT FROM AUTHOR]
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- 2020
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17. Síndrome Serotoninérgico
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Melissa Mora Azofeifa, Juan Carlos Vega Chaves, Sinaí Vásquez Jiménez, and Fabiola Arias Díaz
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serotonina ,síndrome serotoninérgico ,inhibidores de la recaptación de serotonina ,alteraciones autonómicas ,anomalías neuromusculares ,Medicine - Abstract
El síndrome serotoninérgico es una reacción medicamentosa adversa potencialmente letal, que resulta del uso terapéutico de algún fármaco, sobredosis intencional o interacciones farmacológicas involuntarias. Por lo tanto, el síndrome es una consecuencia predecible del exceso de agonismo serotoninérgico de los receptores del sistema nervioso central y del sistema nervioso periférico. Este exceso de serotonina produce un espectro de hallazgos y manifestaciones clínicas que pueden variar desde leves a síntomas severos que amenazan la vida de los pacientes. Por lo que resulta de suma importancia reconocer el síndrome para su diagnóstico temprano y abordaje más adecuado, pues repercute significativamente en el pronóstico. En este documento se realiza un repaso de los aspectos más importantes del síndrome, su diagnóstico y tratamiento.
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- 2019
18. Effect of postictal process in motor deficit and monoaminergic concentration in hippocampus, cerebellum, and cortex.
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Avila-Luna, Alberto, Bueno-Nava, Antonio, Cortes-Altamirano, José Luis, Reyes-Long, Samuel, Bandala, Cindy, and Alfaro-Rodríguez, Alfonso
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SEROTONIN , *MONOAMINE oxidase , *HIPPOCAMPUS (Brain) , *CEREBRAL cortex , *BRAIN damage , *LIQUID chromatography , *AMINO acid neurotransmitters - Abstract
Introduction. Systemic administration of pentylenetetrazole (PTZ) causes brain damage (BD), and triggers a series of morphological and neurochemical changes, which in turn bring about behavioral, cognitive, and motor deficits. Serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels are controlled by various brain structures and these levels are related to motor activity; however, the concentration of these neurotransmitters during the postictal process remains unknown. Objective. We investigated the concentration of 5-HT, NA and DA in the hippocampus, cerebellum, and cortex on motor deficit during the postictal stage. Method. Eighteen male Wistar rats (300 g) assigned to two groups: control (n = 9, saline solution) and experimental (n = 9, PTZ) were used. Myoclonic shakes were counted and motor behavior assessments were recorded during three hours post PTZ injection (90 mg/kg). The cortex, cerebellum, and hippocampus of each rat were dissected to determine the 5-HT, DA, and NA concentration by high performance liquid chromatography. Results. PTZ induced a significant increase in total 5-HT and DA levels in the hippocampus and cortex; in the cerebellum there was a significant increase in the concentration of 5-HT and NA. The presence of myoclonic shakes as well as a marked motor deficit in the experimental group were significantly different in comparison to the control. Discussion and conclusion. 5-HT modifies the concentration of other monoamines directly involved in motor aspects such as NA and DA in the hippocampus, cerebellum, and cortex during the postictal process. [ABSTRACT FROM AUTHOR]
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- 2019
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19. Neurobiología de la agresión y la violencia
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Joaquín Ortega-Escobar and Miguel Ángel Alcázar-Córcoles
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Agresión ,Violencia ,Hipotálamo ,Amígdala ,Corteza prefrontal ,Serotonina ,Jurisprudence. Philosophy and theory of law ,K201-487 ,Psychology ,BF1-990 - Abstract
La neurobiología de la agresión y la violencia es de interés para la psicología jurídica porque buena parte de la conducta delictiva tiene componentes violentos. En esta revisión se definen en primer lugar ambos conceptos, para diferenciar a continuación los tipos de agresión (impulsiva vs. instrumental) que aparecen en la literatura científica y finalmente analizar las estructuras nerviosas que según los estudios sobre lesiones cerebrales o de neuroimagen están asociadas con la agresión. Esta revisión destaca: a) las estructuras subcorticales como el hipotálamo/tronco del encéfalo, donde se genera la conducta agresiva y la amígdala, implicada en procesar estímulos emocionalmente destacados; b) las estructuras corticales como la corteza prefrontal (que comprende la corteza orbitofrontal, la corteza prefrontal ventromedial y la corteza cingulada anterior), que parecen ser hipofuncionales en los sujetos violentos. Por último, se revisan estudios sobre el papel del neurotransmisor serotonina en la manifestación del comportamiento agresivo.
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- 2016
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20. Baja excreción urinaria de Serotonina como índice de malnutrición.
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Luis A. Sobrevilla, Irma Romero, Emilio Castañeda, and César Horta
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excreción urinaria ,serotonina ,malnutrición materna ,malnutrición en feto ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Fragmento INTRODUCCION El impacto de la malnutrición materna en el feto no necesita ser enfatizado: es bien conocido que determina un incremento considerable en la morbilidad y mortalidad durante el período neonatal y de una mayor trascendencia, que ella afecta un período muy importante en el desarrollo del cerebro y otras importantes estructuras del feto, como ha sido demostrado por Winninck y otros. Por estas razones y para iluminar otras áreas de nuestra investigación sobre el embarazo en la altura, nos hemos interesado en la búsqueda de parámetros bioquímicos que puedan ser de ayuda en indicar cuáles son los fetos que están sufriendo de manera importante por la malnutrición materna.
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- 2018
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21. Cardiopulmonary parameters in propofol- or thiopental-anesthetized dogs induced to pulmonary hypertension by serotonin
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P. C. Ferro Lopes, N. Nunes, D. P. Paula, C. T. D. Nishimori, J. V. Moro, E. D. V. Conceição, and P. S. P. Santos
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cão ,anestesia intravenosa total ,índice biespectral ,monitoramento ,serotonina ,Animal culture ,SF1-1100 - Abstract
ABSTRACTThe cardiopulmonary changes in propofol- or thiopental-anesthetized dogs induced to pulmonary hypertension (PH) were evaluated. Twenty adult animals were randomly assigned to two groups: propofol group (PG) and thiopental group (TG). In PG, propofol was used for induction (8(0.03mg.kg-1) and anesthesia maintenance (0.8mg.kg-1.minute-1), while, in TG, thiopental was used (22±2.92mg.kg-1; 0.5mg.kg-1.minute-1, respectively). Mechanical ventilation using time cycle was started. PH was induced by administration of serotonin (5HT) (10µg.kg-1 and 1mg.kg-1.hour-1) through a thermodilution catheter positioned in the pulmonary artery. The measurements were performed before administration of 5HT (T0), after 30 minutes (T30), then at 15-minute intervals (T45, T60, T75 and T90). No differences between groups were registered for systolic (sPAP) and mean pulmonary arterial pressure (mPAP), mean arterial pressure (MAP), total peripheral resistance index (TPRI) and pulmonary vascular resistance index (PVRI). In PG, sPAP and mPAP increased from T30. While in TG, sPAP and mPAP increased from T75. In PG, heart rate (HR) increased from T30, in which PG was higher than TG. The TPRI values decreased from T30 in PG, and in TG, at T45, T60 and T90. In PG, at T0, PVRI was lower than at other times. In PG, arterial partial pressures of oxygen (PaO2) decreased from T60 and alveolar-arterial oxygen gradient (PA-aO2) increased at T60. In TG, at T0 PaO2 was higher than at T30, T45, T60 and T90, while PA-aO2 at T0 was lower than at T90. From T30 to T90, TG showed higher PaO2 means and lower arterial partial pressures of carbon dioxide (PaCO2) values when compared to PG. In PG, from T30, PaCO2 increased, while in TG this parameter was stable. In conclusion, thiopental anesthesia attenuated the cardiopulmonary changes resulting from serotonin-induced PH, probably by attenuation of vasoconstriction and bronchoconstriction.
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- 2015
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22. Avaliação dos efeitos de 5-hidroxitriptofano em-hidroxibenzilhidrazine associados a Lactobacillus spp. na morfometria intestinal e imunomarcação de serotonina em frangos de corte desafiados com Salmonella Enteridis
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Taís C. Donato, Ana Angelita S. Baptista, Bruna D. Smaniotto, Keila C.O.D. Garcia, Adriano S. Okamoto, Julio L. Sequeira, and Raphael L. Andreatti Filho
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Serotonina ,Salmonella Enteritidis ,Lactobacillus spp. ,morfometria intestinal ,frangos de corte. ,Veterinary medicine ,SF600-1100 - Abstract
Resumo As células enterocromafins são um dos componentes da mucosa intestinal que liberam serotonina para o lúmen, promovendo atividades secretórias e crescimento celular de vários tecidos, incluindo vilosidades intestinais. O presente estudo avaliou as influências do 5-hidroxitriptofano (5HTP) e do m-hidroxibenzilhidrazine (NSD1015), associados a Lactobacillus spp., sobre o peso corporal e o desenvolvimento das vilosidades intestinais na porção proximal do duodeno de frangos de corte desafiados com Salmonella Enteritidis. Verificou-se também se a presença de Lactobacillus spp. e Salmonella Enteritidis influenciaram a imunomarcação de serotonina no duodeno e, para isso, o estudo foi dividido em dois experimentos, com e sem desafio por S. Enteritidis. No Experimento 1, em aves sem desafio, os pesos corporais não diferiram significantemente (p>0,05) e, no Experimento 2, aves com desafio, os tratamentos com o precursor isolado e associado a Lactobacillus spp. determinaram maior peso corporal das aves. Nos dois experimentos, as aves tratadas com 5HTP apresentaram aumento na densidade e altura das vilosidades no duodeno, sugerindo a atuação de 5HTP como um agente trófico. A administração de Lactobacillus spp. também determinou altura maior de vilosidades duodenais. Quanto a imunomarcação de serotonina, as aves tratadas com Lactobacillus spp. no Experimento 1 e as aves tratadas com Lactobacillus spp. e desafiadas com S. Enteritidis no Experimento 2, apresentaram valores superiores aos demais tratamentos, sugerindo que a presença destas bactérias promove maior liberação de serotonina para o duodeno, porém o mecanismo exato de como este processo ocorre necessita ser mais elucidado.
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- 2015
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23. Stosowanie wenlafaksyny w dawkach podzielonych – opis kazuistyczny
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Łukasz Święcicki
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wenlafaksyna ,serotonina ,noradrenalina ,depresja ,tolerancja leku ,Medicine - Abstract
Wenlafaksyna jest lekiem o co najmniej dwóch istotnych mechanizmach działania przeciwdepresyjnego. Hamowanie wychwytu zwrotnego serotoniny (5-HT) ujawnia się już podczas stosowania niskich dawek, a hamowanie wychwytu zwrotnego noradrenaliny – dopiero przy dawkach istotnie wyższych. Za punkt odcięcia przyjmuje się na ogół dawkę 225 mg na dobę, choć zmiana z jednego mechanizmu działania na dwa ma najprawdopodobniej charakter spektralny. Możliwe, że w dawkach powyżej 375 mg na dobę lek wykazuje również działanie dopaminergiczne, ale tak duże dawki wenlafaksyny nie są zalecane przez producenta. Stosowanie wyższych dawek przekłada się na większą skuteczność przeciwdepresyjną leku. Należy jednak pamiętać, że zmiana dawki może być związana z ujawnieniem się odmiennego profilu działań niepożądanych (choć zależy to także od indywidualnej wrażliwości pacjenta). Działanie serotoninergiczne bywa odbierane jako uspokajające, sedujące, powodujące nadmierną senność, a nawet zobojętnienie i apatię. Działanie noradrenergiczne może z kolei wywoływać uczucie nadmiernego pobudzenia i zaburzenia snu. To, czy dane działanie jest odczuwane jako niewpływające na funkcjonowanie, czy też jako trudne do zniesienia, zależy ponadto od pory dnia, w której występuje. Działanie nasenne pacjent uzna za korzystne wieczorem, natomiast działanie rozbudzające – rano. Wydaje się, że pora podawania wenlafaksyny może wpływać na subiektywną tolerancję leku. W artykule opisano dwie sytuacje ilustrujące ten punkt widzenia. Nie jest do końca jasne, dlaczego pacjenci odczuwają działanie leku najsilniej wkrótce po jego przyjęciu (nie da się wykluczyć swoistego efektu placebo). Mimo to w przypadku wielu chorych subiektywna tolerancja wenlafaksyny bez wątpienia ma związek ze sposobem podawania leku; lekarze powinni brać tę okoliczność pod uwagę.
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- 2015
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24. Assessment of serotonergic system in formation of memory and learning.
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da Silva, J. C., Amorim, C. A. M., Rodrigues, G. P., Dal Pai, J., Zambrano, L. I., and Trindade Filho, E. M.
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SEROTONINERGIC mechanisms ,IMPLICIT memory ,NEUROPLASTICITY ,STEREOTAXIC techniques ,LABORATORY rats - Abstract
Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2018
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25. The Role of Histamine and Serotonin in the Control of Vascular Motricity of the Anterior Ocular Segment - Review of the Literature from 1997 to 2018.
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Lunca, Dragos-Constantin, Paunescu, Horia, Coman, Laurentiu, and Fulga, Ion
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SEROTONIN , *HISTAMINE , *VASOCONSTRICTION - Abstract
Histamine and serotonin, besides known systemic effects, can influence vascular tone at the eye level. The review of the literature from 1997 to 2018 suggests that these ocular effects are very variable -both vasodilation and vasoconstriction. Specific agonists or antagonists acting in the histamine and serotonin domains, are probably more useful than endogenous substances as working tools for discovering the functional elements involved in regulating ocular vascular tone. Knowing that intraocular pressure regulation also depends on the vascular tone of the anterior ocular segment, some of the substances under review may be candidates for potential intraocular pressure lowering drugs. [ABSTRACT FROM AUTHOR]
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- 2018
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26. Pharmacodynamics of Serotonin. Emphasis on 5HT-3 Antagonists and SSRI Medication (II).
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Costescu, Mihnea, Paunescu, Horia, Vasile, Sorina, Zugravu, Aurelian, Coman, Oana Andreia, and Fulga, Ion
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- *
PHARMACODYNAMICS , *SEROTONIN , *SEROTONIN uptake inhibitors - Abstract
This paper is a specialized literature review of the pharmacology of serotonin, that focuses on pharmacodynamics. The main aspects discussed here are the metabolism and transport of serotonin, along with the structure and functions of 5-HT receptors and their clinical implications. We also included the substances that influence the serotonin neurotransmission and the autacoid function, which may be prove useful in treating various disorders. In this second part of the review, we present the types of 5-HT receptors (5-HT4, 5-HT5, 5-HT6, 5-HT7), along with the tendencies and prospects in influencing serotonin transporter (SERT) through selective serotonin reuptake inhibitors (SSRIs). In order to achieve better safety and effectiveness of antidepressant therapy, recent research is studying substances that not only target SERT, but can also act on certain serotonergic receptors. [ABSTRACT FROM AUTHOR]
- Published
- 2018
27. Disminución de los niveles de serotonina tras una intervención de estilo de vida en niños obesos: asociación con glucosa y medidas antropométricas.
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Ojeda-Rodríguez, Ana, Morell-Azanza, Lydia, Azcona-Sanjulián, María Cristina, Alfredo Martínez, J., Ramírez, María J., Marti, Amelia, Martínez, J Alfredo, and Ramirez, María J
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- *
SEROTONIN , *REGULATION of body weight , *GLUCOSE metabolism , *WEIGHT loss , *BLOOD sugar , *ANTHROPOMETRY , *CHILDHOOD obesity - Abstract
Background: serotonin signaling participates in body weight regulation and glucose metabolism. However, little information is available on circulating serotonin levels in obese subjects after a weight loss program. We aimed to assess the effect of a lifestyle intervention on serotonin levels in obese children and possible associations with anthropometric and blood glucose measurements.Methods: forty-four obese children were enrolled in a ten-week lifestyle intervention consisting of a moderate caloric restriction diet, nutritional education and familial involvement. They were distributed according to the weight loss response. Subjects who lost > 0.5 BMI-SDS were considered as high responders (HR; n = 22) and those who lost ≤ 0.5 BMI-SDS, as low responders (LR; n = 22). Anthropometric, biochemical parameters and plasma serotonin levels were measured as pre and post-intervention values.Results: obese children (HR and LR groups) were able to reduce anthropometric indices and to improve glucose profile after the intervention. Interestingly, plasma serotonin levels were significantly (p ˂0.05) reduced in all subjects (-35.14 nmol/l HR group and -30.63 nmol/l LR group). Moreover, multiple-adjusted regression models showed a significant association between pre-intervention (R2 = 0.224, B = 0.047; p = 0.004) and post-intervention (R2 = 0.140; B = 0.055; p = 0.042) plasma serotonin and glucose levels. In addition, in HR subjects changes in plasma serotonin were associated with changes in glucose levels (R2 = 0.292; b = 0.04; p = 0.045). Interestingly, pre and post-intervention plasma serotonin levels were inversely associated (p ˂0.05) with anthropometric measures.Conclusions: serotonin levels were reduced after a lifestyle intervention independently of the program response. Moreover, plasma serotonin levels were associated with glucose and anthropometric measures in obese children. [ABSTRACT FROM AUTHOR]- Published
- 2018
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28. Regulation of Expression of Cannabinoid CB2 and Serotonin 5HT1A Receptor Complexes by Cannabinoids in Animal Models of Hypoxia and in Oxygen/Glucose-Deprived Neurons
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Jaume Lillo, Iu Raïch, Laura Silva, David A. Zafra, Alejandro Lillo, Carlos Ferreiro-Vera, Verónica Sánchez de Medina, José Martínez-Orgado, Rafael Franco, and Gemma Navarro
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Anoxemia ,Serotonin ,Organic Chemistry ,Anoxèmia ,Serotonina ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Ischemia ,downregulation ,heteromers ,hypoxia ,ischemia ,phytocannabinoids ,serotonin ,Isquèmia ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Background: Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB2 and serotonin 5HT1A receptors included. These two receptors may interact to form heteromers (CB2–5HT1A-Hets) that are also a target of CBD. Aims: We aimed to assess whether the expression and function of CB2–5HT1A-Hets is affected by CBD in animal models of hypoxia of the neonate and in glucose- and oxygen-deprived neurons. Methods: We developed a quantitation of signal transduction events in a heterologous system and in glucose/oxygen-deprived neurons. The expression of receptors was assessed by immuno-cyto and -histochemistry and, also, by using the only existing technique to visualize CB2–5HT1A-Hets fixed cultured cells and tissue sections (in situ proximity ligation PLA assay). Results: CBD and cannabigerol, which were used for comparative purposes, affected the structure of the heteromer, but in a qualitatively different way; CBD but not CBG increased the affinity of the CB2 and 5HT1A receptor–receptor interaction. Both cannabinoids regulated the effects of CB2 and 5HT1A receptor agonists. CBD was able to revert the upregulation of heteromers occurring when neurons were deprived of oxygen and glucose. CBD significantly reduced the increased expression of the CB2–5HT1A-Het in glucose/oxygen-deprived neurons. Importantly, in brain sections of a hypoxia/ischemia animal model, administration of CBD led to a significant reduction in the expression of CB2–5HT1A-Hets. Conclusions: Benefits of CBD in the hypoxia of the neonate are mediated by acting on CB2–5HT1A-Hets and by reducing the aberrant expression of the receptor–receptor complex in hypoxic-ischemic conditions. These results reinforce the potential of CBD for the therapy of the hypoxia of the neonate.
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- 2022
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29. Food restriction beginning at lactation interferes with the cellular dynamics of the mucosa and colonic myenteric innervation in adult rats
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JOÃO PAULO F. SCHOFFEN, FERNANDO A. VICENTINI, CAROLINA G. MARCELINO, EDUARDO J.A. ARAÚJO, MARIA M.D. PEDROSA, and MARIA R.M. NATALI
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células enteroendócrinas ,restrição alimentar ,células caliciformes ,morfologia intestinal ,neurônios mioentéricos ,serotonina ,Science - Abstract
The effects of food restriction (FR) on the morphoquantitative aspects of the wall and myenteric neurons of the proximal colon in adult rats were analysed. FR was imposed by duplication of the experimental brood size in relation to the control brood during lactation. The FR group received a 50% reduction of food from weaning until 90 days of age. Samples of the colon underwent histological processing to morphometrically analyze the crypts, muscularis mucosae, tunica mucosa, and muscularis externa. We determined the number of goblet cells and serotoninergic enteroendocrine cells, and morphoquantitatively studied the myenteric neuronal population. FR caused hypertrophy in the tunica mucosa, increase in crypt depth and in the muscular layer of the mucosa, a decrease in the thickness of the tunica muscularis and in the number of goblet cells and an increase in serotoninergic cells. A higher neuronal density in the ganglia and a reduction of the cell profile area were observed in the FR group. FR imposed since lactation led to hypertrophy of the tunica mucosa, a reduction of neutral mucin production, atrophy of the tunica muscularis, and an increase in the survival neuronal in adult rats, attributable to an increase in the number of serotoninergic enteroendocrine cells in mucosa.
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- 2014
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30. The neuroendocrine markers assay and the glycemia profile in patients with neuroendocrine tumors under octreotide therapy: a 2 years study / Determinarea markerilor neuroendocrini şi a profilului glicemic la pacienţii cu tumori neuroendocrine în tratament cu octreotid
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Poiană Cătălina, Păun Diana, and Carsote Mara
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chromogranin a ,neuroendocrine tumor ,serotonin ,cromogranina a ,tumora neuroendocrina ,serotonina ,Medicine - Abstract
Tumorile neuroendocrine (NET) sunt mult mai frecvente în ultimele decade. Unul din intrumentele majore de evaluare în această patologie este reprezentat de dozarea markerilor neuroendocrini precum cromogranina A, serotonina, acidul 5-hidroxi indolacetic urinar şi enolaza neuronal specifică. Aceştia se schimbă cu progresia tumorală, indiferent de terapie. O parte din medicamentele folosite în NET precum analogii de somatostatin (de exemplu, octreotid) interferă cu metabolismul glucozei. Obiectiv. Am analizat într-un studiu retrospectiv de-a lungul a 2 ani dinamica markerilor NET şi profilul glicemic. Material si metode.Toţi pacienţii au avut cel puţin o evaluare pe an. Rezultate. 9 pacienţi au fost incluşi (5 femei şi 4 bărbaţi), cu o vârstă medie de 57,33 de ani. Perioada de tratament anterior cu octreotid a fost de 18 +/- 14,69 de luni. Doza de octreotid a variat de la 20 la 50 mg lunar. Glicemia s-a modificat nesemnificativ de la bază după 2 ani. Nu s-a înregistrat nici un caz nou de diabet. O pacientă a necesitat insulină pentru diabetul preexistent (dar între timp s-a adaugat şi terapie cu interferon) Cromogranina A a avut valori mari sustinute pentru toate cele 9 cazuri, sugerând progresia bolii. Enolaza neuronal specifică a crescut semnificativ iar serotonina serică şi 5HIIA au crescut considerabil în 2 cazuri cu simptome severe de sindrom carcinoid. Concluzie. Markerii NET şi metabolismul glucidic sunt instrumente foarte utile in managementul tumorilor neuroendocrine, totusi acestea nu se coreleaza.
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- 2014
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31. Quantification of urinary 5-hydroxyindoleacetic acid by in-house nitrosonaphthol reaction compared with nitrosonaphthol micro column chromatography and enzyme-linked immunosorbent assay
- Author
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Joyce Matie Kinoshita da Silva, Rejane Mattar, Carlos Colaúto, and Flair José Carrilho
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ácido 5-hidroxi-indolacético ,ELISA ,tumores carcinoides ,serotonina ,nitrosonaftol ,Pathology ,RB1-214 - Abstract
The aim of this study was to compare the colorimetric "kit" and enzyme-linked immunosorbent assay (ELISA) methods to quantify urinary 5-hydroxyindoleacetic acid through the Goldenberg's technique, exploring the potential of replacing it. 24-hour urine samples were tested by Goldenberg's assay and compared with kits. The agreement was almost perfect for the comparison of Goldenberg's assay with both colorimetric kit, and with ELISA kit, considering ≤ 7.5 mg/24h normal cutoff value. Therefore, both "kits" would be good alternatives to Goldenberg's technique due to practicality and agreement between values.
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- 2014
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32. Serotonergic signaling modulation as a therapeutic strategy for Machado-Joseph disease: finding the molecular traits
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Oliveira, Stéphanie Pereira, Castro, Andreia Cristiana Teixeira, Carvalho, Ana Luísa Monteiro de, and Universidade do Minho
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Serotonin ,Doença de Machado-Joseph (DMJ) ,Ciências Médicas::Ciências da Saúde ,Proteotoxicidade ,Serotonina ,Citalopram ,Proteotoxicity ,Machado-Joseph disease (MJD) - Abstract
Tese de doutoramento em Envelhecimento e Doenças Crónicas, A doença de Machado-Joseph (DMJ) é uma doença autossómica dominante incurável, de início tardio. Caracteriza-se por uma expansão de repetições do tripleto CAG no gene MJD1/ATXN3, que origina proteínas com conformação nativa alterada, promovendo agregação e perda neuronal. É uma doença incapacitante, tendo grande impacto económico e social, sendo urgente o desenvolvimento de terapias. Nesta tese, procurámos estudar o potencial terapêutico da modulação da sinalização serotoninérgica pelo citalopram, um inibidor seletivo da recaptação da serotonina (ISRS), e dos seus mecanismos de ação na DMJ. Investigou-se se o tratamento com citalopram iniciado pós-sintomaticamente seria eficaz em ratinhos transgénicos da DMJ. Observámos que este melhorou a função motora, apesar deste ser menos eficaz que o tratamento pré-sintomático, mostrando impacto limitado na agregação da ATXN3 e na neuroproteção. Para identificar determinantes moleculares subjacentes à supressão da proteotoxicidade via sinalização serotoninérgica, foi realizada uma análise transcriptómica no estriado de ratinhos CMVMJD135 tratados pré-sintomaticamente. Verificou-se uma alteração na sinalização serotoninérgica neste modelo, envolvendo o receptor 5-HT1A e respetivas vias de sinalização, incluindo a proteína de ligação ao elemento de resposta cAMP - CREB, que poderá ser relevante na patogénese e no tratamento desta doença. Também se observou que o citalopram altera os níveis de expressão de genes relacionados com o controlo de qualidade proteico (CQP) e vias auxiliares (ex., degradação, manutenção da conformação e resposta antioxidante), melhorando a homeostase proteica. Estes dados foram corroborados num modelo genético em C. elegans com neurotransmissão serotoninérgica aumentada, via ablação do transportador de serotonina mod-5 em nematodes que expressam a ATXN3 mutante. Foi observada uma recuperação total do perfil transcriptómico dos animais mutantes, confirmando-se este gene como um modificador genético da DMJ em C. elegans. Demonstrou se ainda a ativação de respostas de defesa e de CQP (ex., via lisossomal e autofagia) nestes animais duplos mutantes, incluindo algumas vias comuns a animais com longevidade aumentada. Resumindo, demonstrou-se que a modulação serotoninérgica foi protetora na DMJ mesmo após início dos sintomas, constituindo o citalopram uma estratégia promissora a ser avaliada em ensaios clínicos humanos. Este trabalho também levantou a hipótese duma alteração na transmissão serotoninérgica na DMJ e apontou vias candidatas que contribuem para o efeito benéfico da modulação desta sinalização em contrabalançar os efeitos proteotóxicos mediados pela ATXN3 mutante., Machado-Joseph disease (MJD) is an autosomal dominantly inherited late onset disorder with no disease-modifying treatment available. It is characterized by an expansion of the CAG repeat in the MJD1/ATXN3 gene, triggering the appearance of misfolded protein species, leading to aggregation and neuronal loss. It is an incapacitant disease, requiring full-time care of the patient, with consequent strong economic and social impact, being urgent to find to new therapies to improve patients’ quality of life. In this thesis, we aimed at further addressing the therapeutic potential of serotonergic signaling modulation by citalopram treatment, a selective serotonin reuptake inhibitor (SSRI), and to uncover its mechanism(s) of action in MJD. We investigated whether post-symptomatic citalopram treatment initiation in MJD transgenic mice would show efficacy. We observed that it still improved motor behavior, although not as strongly as pre-symptomatic treatment, with limited impact on ATXN3 aggregation and neuroprotection. To find the molecular determinants underlying serotonergic signaling-mediated suppression of proteotoxicity, a transcriptomic analysis of the striatum of pre-symptomatically citalopram and vehicle-treated MJD mice was performed. Results indicated that serotonergic signaling is altered in MJD mice and that the serotonin 5-HT1A receptor and its signal-transduction pathways, including the cAMP response element-binding protein (CREB) transcription factor, could be relevant in MJD pathogenesis and treatment. It showed that citalopram can alter the levels of several protein quality control (PQC)-related genes and auxiliary pathways (e.g., degradation, folding, and antioxidant response), enhancing proteostasis capacity. This was further confirmed by RNA-sequencing of a genetic C. elegans model of increased serotonergic neurotransmission, in which the serotonin transporter mod-5 was ablated in the background of MJD pathology, mimicking citalopram action. This ablation rescued the transcriptomic profile of mutant ATXN3 animals, establishing mod-5 as genetic modifier of MJD in C. elegans. Activation of defense responses and PQC-related machinery (e.g., lysosomal pathway and autophagy) were observed in double mutant animals, a subset of which are also found in long-lived animals. In summary, this work demonstrated that modulation of serotonergic signaling protected against MJD pathogenesis even after symptom onset, evidencing citalopram as a promising therapeutic compound to be evaluated in human clinical trials. It also raised the hypothesis of an altered serotonergic transmission in the disease and suggested candidate pathways which contribute to the beneficial effect of serotonergic signaling modulation in offsetting mutant ATXN3-mediated proteotoxicity., Financial support was provided by grants from the Portuguese Foundation for Science and Technology (FCT): Inter-University Doctoral Programme in Ageing and Chronic Disease fellowship (PD/BD/127818/2016) to S. Oliveira; and by FEDER, through the Competitiveness Internationalization Operational Programme (POCI) under the scope of the project POCI-01-0145-FEDER-031987 to A. Teixeira-Castro, supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); and by National funds, through the FCT - project UIDB/50026/2020 and UIDP/50026/2020. This work was also funded through the National Ataxia Foundation (NAF), USA, and by the U.S. Department of Defense (DoD) - grant award number: W81XWH-19-1-0638.
- Published
- 2022
33. The role of serotonin in regulation of benign prostatic growth - implications for benign prostatic hyperplasia etiology
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Dias, Emanuel Carvalho, Correia-Pinto, Jorge, and Universidade do Minho
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Androgen receptor ,Serotonin ,Benign prostatic hyperplasia ,Serotonina ,Hiperplasia benigna da próstata ,Receptor androgénios ,Ciências Médicas::Medicina Clínica - Abstract
Tese de doutoramento em Medicina, O envelhecimento e a presença de testosterona causa quase inexoravelmente hiperplasia benigna da próstata (HBP) nos homens, no entanto a etiologia da HBP é largamente desconhecida. A serotonina (5-HT) é uma amina biogénica produzida pelas células neuroendócrinas da próstata e está presente em altas concentrações na próstata normal, mas a sua função na fisiologia prostática é desconhecida. A evidência acumulada tem demonstrado que as células neuroendócrinas e a 5-HT estão diminuidas ou ausentes no tecido com HBP comparativamente à próstata normal. Aqui, nós demonstramos que a 5-HT é um forte regulador negativo do crescimento prostático. In vitro, a 5-HT inibe na próstata de rato o processo de morfogénese por ramificação e esta função reguladora negativa é associada à diminuição do receptor de androgénio (AR). Este mecanismo inibirtório da 5-HT está também presente em células humanas de próstata normal e próstata com HBP, mas apenas em linhas celulares que expressam o AR e tratadas com testosterona. Uma vez que a produção periférica de 5-HT é especificamente regulada pela triptofano hidroxilase 1 (Tph1), nós usamos ratinhos knockout para a Tph1 e demonstramos que estes ratinhos exibem uma próstata com maior massa comparativamente a ratinhos selvagem. Demonstrámos também aqui que o tratamento de ratinhos knockout para a Tph1 com 5-HT restaura a massa prostática para os níveis de ratinhos selvagem. Finalmente, nós demonstramos neste trabalho que a suplementação oral com uma dieta rica em triptofano diminui a massa prostáticas em ratinhos. Uma vez que a serotonina está diminuida na HBP nós apresentamos aqui evidência que liga a deplecção de serotonina à etiologia da HBP através de modulação do recetor de androgénios. A via serotoninérgica prostática deverá ser explorada como um novo alvo terapêutico para a HBP., Aging and the presence of testosterone cause almost inexorably benign prostatic hyperplasia (BPH) in human males, however the etiology of BPH is largely unknown. Serotonin (5-HT) is a biogenic amine produced by neuroendocrine prostatic cells and present in high concentration in normal prostate but its function in prostate physiology is unknown. Evidence have demonstrated that neuroendocrine cells and 5-HT are decreased or absent in BPH tissue comparatively to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth. In vitro, 5-HT inhibits rat prostate branching morphogenesis and this negative regulatory function is associated with a down-regulation of androgen receptor (AR). This 5-HT inhibitory mechanism was also present in human cells of normal prostate and BPH, but only in cell lines expressing AR and treated with testosterone. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1 (Tph1), we used Tph1 knockout mice and showed that this mice have higher prostate mass comparatively to wild-type. We show here also that treatment of Tph1 knockout mice with 5-HT restores prostate mass to levels of wild-type. Finally, we demonstrate in this work that oral supplementation with a tryptophan rich diet decreases de prostate mass in mice. As serotonin is decreased in BPH we present here evidence that links 5-HT depletion to BPH etiology through modulation of AR. Serotoninergic prostate pathway should be explored as a completely new therapeutic target for BPH., This work has been developed under the scope of the projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) and Bolsa de Doutoramento José de Mello Saúde.
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- 2022
34. Pharmacodynamics of Serotonin. Emphasis on 5HT-3 Antagonists and SSRI Medication (II).
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Costescu, Mihnea, Paunescu, Horia, Vasile, Sorina, Zugravu, Aurelian, Coman, Oana Andreia, and Fulga, Ion
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PHARMACODYNAMICS , *SEROTONIN , *NEURAL transmission , *THERAPEUTICS - Abstract
This paper is a specialized literature review of the pharmacology of serotonin, that focuses on pharmacodynamics. The main aspects discussed here are the metabolism and transport of serotonin, along with the structure and functions of 5-HT receptors and their clinical implications. We also included the substances that influence the serotonin neurotransmission and the autacoid function, which may be prove useful in treating various disorders. In this second part of the review, we present the types of 5-HT receptors (5-HT4, 5-HT5, 5-HT6, 5-HT7), along with the tendencies and prospects in influencing serotonin transporter (SERT) through selective serotonin reuptake inhibitors (SSRIs). In order to achieve better safety and effectiveness of antidepressant therapy, recent research is studying substances that not only target SERT, but can also act on certain serotonergic receptors. [ABSTRACT FROM AUTHOR]
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- 2017
35. Efeitos do exercício físico sobre os níveis séricos de serotonina e seu metabólito na fibromialgia: um estudo piloto randomizado
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Valéria Valim, Jamil Natour, Yangming Xiao, Abraão Ferraz Alves Pereira, Beatriz Baptista da Cunha Lopes, Daniel Feldman Pollak, Eliana Zandonade, and Irwin Jon Russell
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Fibromialgia ,Exercício ,Serotonina ,5HIAA ,5HT ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Avaliar os efeitos do treinamento aeróbico e do alongamento sobre os níveis séricos de serotonina (5-HT) e seu principal metabólito ácido 5-hidroxiindolacético (5-HIAA). Foram randomizadas 22 mulheres com fibromialgia (FM) em uma de duas modalidades de exercício (exercício aeróbico de caminhada ou exercício de alongamento) a serem realizadas três vezes por semana, por 20 semanas. Os níveis séricos de 5-HT e 5-HIAA foram avaliados antes e após o programa de exercícios por cromatografia líquida de alta eficiência (CLAE) com detecção colorimétrica. A análise de grupo (pré-pós) mostrou que os níveis séricos de 5-HT e 5-HIAA mudaram significativamente no grupo aeróbico durante o período de 20 semanas de terapia (5-HT: p = 0,03; 5-HIAA: p = 0,003). No grupo alongamento, contudo, não foi observada qualquer alteração estatisticamente significativa (5-HT: p = 0,491; 5-HIAA: p = 0,549). Comparações estatísticas das medidas de laboratório entre os grupos constataram que o treinamento aeróbico foi superior ao alongamento, aumentando significativamente os níveis de 5-HIAA (teste F - 6,61; p = 0,01); porém, a diferença média entre os grupos a respeito dos níveis de 5-HT não atendeu aos critérios de relevância (teste F = 3,42; p = 0,08). O treinamento aeróbico aumenta os níveis de 5-HIAA e 5-HT e poderia explicar porque o exercício aeróbico pode melhorar os sintomas de pacientes com síndrome de fibromialgia mais que o exercício de alongamento.
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- 2013
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36. [Untitled]
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Melissa Araújo Ulhoa, Nyam Florencio da Silva, José Guilherme Pinheiro Pires, and Henrique de Azevedo Futuro Neto
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núcleo obscuro da rafe ,serotonina ,neurônios serotoninérgicos ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
In mammalian, several evidences suggest that central serotonin participates in thermoregulation. Nucleus raphe obscurus (NRO), a serotonergic nucleus, has been recognized to be the source of generation of various hemodynamic patterns in different behavioral conditions, but its involvement in thermoregulation is unclear. In the present study, extracellular action potentials of NRO neurons were recorded in anesthetized rats, which were submitted to cold and warm stimuli in the tail. The firing rate of the neurons was compared before and after each stimulation. It was found that 59% of the neurons submitted to a cold stimulus trial had a significant increase in their firing frequency, while 48% of the neurons submitted to warm stimulation trial were inhibited. The opposite responses in neuronal activity of NRO units to cooling or heating suggest that these cells are involved in producing the homoeothermic vascular adaptations secondary to changes in cutaneous temperature in the rat tail.
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- 2013
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37. [Untitled]
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Melissa Araújo Ulhoa, Nyam Florencio da Silva, José Guilherme Pinheiro Pires, and Henrique de Azevedo Futuro Neto
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núcleo obscuro da rafe ,serotonina ,neurônios serotoninérgicos ,nucleus raphe obscurus ,serotonin ,serotonergic neurons ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
In mammalian, several evidences suggest that central serotonin participates in thermoregulation. Nucleus raphe obscurus (NRO), a serotonergic nucleus, has been recognized to be the source of generation of various hemodynamic patterns in different behavioral conditions, but its involvement in thermoregulation is unclear. In the present study, extracellular action potentials of NRO neurons were recorded in anesthetized rats, which were submitted to cold and warm stimuli in the tail. The firing rate of the neurons was compared before and after each stimulation. It was found that 59% of the neurons submitted to a cold stimulus trial had a significant increase in their firing frequency, while 48% of the neurons submitted to warm stimulation trial were inhibited. The opposite responses in neuronal activity of NRO units to cooling or heating suggest that these cells are involved in producing the homoeothermic vascular adaptations secondary to changes in cutaneous temperature in the rat tail.A termorregulação em mamíferos envolve a participação da serotonina. O núcleo obscuro da rafe (NRO), que é serotoninérgico, participa do controle autonômico, mas seu envolvimento na termorregulação é incerto. Neste estudo, registramos potenciais de ação extracelulares de neurônios do NRO em ratos anestesiados nos quais a cauda foi submetida a estímulos de calor ou frio. A frequência de disparo dos neurônios foi comparada antes e depois dos estímulos. O grupo controle não apresentou modificação da frequência de disparo, enquanto que 59% dos neurônios registrados em animais submetidos a estímulo de frio tiveram sua frequência aumentada. Por outro lado, 48% dos animais submetidos a estímulo de calor tiveram sua frequência de disparo diminuída. As respostas opostas da frequência de disparo em neurônios de animais submetidos à estimulação com frio e calor sugere que estes neurônios estejam envolvidos na geração de respostas hemodinâmicas, que são coerentes com a termorregulação nesta espécie.
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- 2013
38. Efeitos dos antidepressivos tricíclicos, inibidores seletivos da recaptação da serotonina e inibidores da recaptação de serotonina e noradrenalina na superfície ocular
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Ayna Sariyeva Ismayilov and Guler Celikel
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Serotonin reuptake inhibitors ,Serotonin ,Síndromes do olho seco ,Depression ,Serotonina ,Pharmaceutical preparations ,Chronic pain ,General Medicine ,tricyclic ,Norepinefrina ,Anxiety ,Dry eye syndromes ,Ophthalmology ,Inquéritos e questionários ,Norepinephrine ,Antidepressive agents ,Antidepressivos tricíclicos ,Depressão ,Inibidores de recaptação de serotonina ,Ansiedade ,Dor crônica ,Preparações farmacêuticas ,Surveys and questionnaires - Abstract
Purpose: This study aimed to investigate the effects of tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective serotonin noradrenaline reuptake inhibitors on the ocular surface. Methods: The study included 330 eyes of 165 patients using antidepressants and 202 eyes of 101 controls. Tear fluid breakup time, Schirmer I test, and Ocular Surface Disease Index (OSDI) questionnaire were administered. Beck Depression Inventory and Beck Anxiety Inventory were applied to record drug use, dosages, psychiatric disease duration, and remission time. Results: Mean tear fluid breakup time was 14.29 ± 4.81 (4-26) sec, and Schirmer I test value was 16.05 ± 5.89 (2-28) mm in study group. Tear fluid breakup time was 18.16 ± 2.12 (15-24) sec and Schirmer I test value was 16.64 ± 2.31 (15-24) mm in control group (p
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- 2022
39. Bipolar disorder and Premenstrual Syndrome or Premenstrual Dysphoric Disorder comorbidity: a systematic review Comorbidade entre o Transtorno Bipolar e Síndrome Pré-menstrual ou Transtorno Disfórico Pré-menstrual: uma revisão sistemática
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Patricia Carvalho Cirillo, Roberta Benitez Freitas Passos, Mario Cesar do Nascimento Bevilaqua, Jose Ramón Rodriguez Arras López, and Antônio Egidio Nardi
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Transtorno Bipolar ,Estrógenos ,Síndrome Pré-Menstrual ,Progesterona ,Serotonina ,Bipolar Disorder ,Estrogens ,Premenstrual Syndrome ,Progesterone ,Serotonin ,Psychiatry ,RC435-571 - Abstract
OBJECTIVE: This article aims to review the comorbidity of premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) and bipolar disorder (BD), identify variables requiring further investigation and to remind physicians that special care is required for diagnosis and therapy. METHOD: A systematic review of articles published from 1987 to February 2012 was conducted in the Medline database with the following terms: (premenstrual syndrome OR premenstrual dysphoric disorder OR premenstrual) AND (bipolar OR mania OR manic). Seventeen articles were analyzed. RESULTS: PMS and PMDD were most often comorbid among BD-II patients and vice versa. Moreover, patients with PMS or PMDD also have an increased risk of having BD-I. In addition, bipolar women susceptible to hormonal changes exhibit more severe symptoms, more frequent relapses and a worse therapeutic response. CONCLUSION: Future investigations should attempt to stabilize hormonal levels through the continuous use of contraceptives to target a reduction in symptom severity. In addition, psychiatrists should note menstrual period dates and compare symptom intensity between the luteal and follicular phases. Finally, PMS and PMDD patients should be studied separately.OBJETIVO: Esse artigo tem como objetivo revisar a comorbidade entre a Síndrome Pré-Menstrual (SPM) ou Transtorno Disfórico Pré-Menstrual (TDPM) e o Transtorno Bipolar (TB), identificar as variáveis que exigem uma investigação mais aprofundada e lembrar os médicos que as mulheres necessitam de cuidados especiais para diagnóstico e tratamento. MÉTODO: Foi realizada uma revisão sistemática de 1987 a fevereiro de 2012 através da base de dados Medline utilizando os seguintes descritores: (premenstrual syndrome OR premenstrual dysphoric disorder OR premenstrual) AND (bipolar OR mania OR manic). Dezessete artigos foram analisados. RESULTADOS: Pacientes com SPM ou TDPM possuem comorbidade com TB-II com maior frequência e vice-versa. Mulheres com SPM ou TDPM também possuem um risco aumentado apresentar TB-I. Além disso, as mulheres bipolares suscetíveis a mudanças hormonais cursam com sintomas mais graves, recaídas mais freqüentes e pior resposta terapêutica. CONCLUSÃO: Futuras investigações devem estabilizar os níveis hormonais com o uso contínuo de contraceptivos na tentativa de diminuir a gravidade dos sintomas. Além disso, psiquiatras devem observar os períodos menstruais e comparar a intensidade dos sintomas entre as fases folicular e lútea. Pacientes com SPM ou TDPM devem ser estudadas separadamente.
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- 2012
40. No association between the HTR1A gene and suicidal behavior: a meta-analysis A não associação entre o gene HTR1A e comportamento suicida: uma metanálise
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Miriam Rivera Angles, Deysi Bermúdez Ocaña, Beatriz Camarena Medellín, and Carlos Tovilla-Zárate
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Suicídio ,Serotonina ,Receptor 1A de Serotonina ,Metanálise ,Suicide ,Serotonin ,Serotonin Receptor 1A ,Meta-Analysis ,Psychiatry ,RC435-571 - Abstract
OBJECTIVE: Dysfunction of serotonin 1A receptors (HTR1A) may play a role in the genesis of suicidal behavior. We studied the association between a functional polymorphism in the HTR1A gene and suicidal behavior. METHOD: We performed a meta-analysis of published genetic association studies by searching through Medline, PubMed, and Web of Science databases to analyze a possible correlation between the rs6295 polymorphism and suicidal behavior in different populations. RESULTS: Four studies comprising a total of nine hundred and fifty seven patients with suicidal behavior and nine hundred and fifty seven controls were the eligible. The G allele of the rs6295 polymorphism may not be associated with suicidal behavior (Random-effects model: OR = 1.08; 95% CI: 0.80-1.45; p(Z) = 0.80) in presence of heterogeneity (Q = 17.84, df = 4, p = 0.0013). In a second analysis that presented no heterogeneity, a negative association was also observed (OR = 0.94; 95%CI: 0.79-1.13; p(Z) = 0.99). CONCLUSION: To our knowledge, the present study is the first meta-analysis searching for a correlation between rs6295 of HTR1A and suicidal behavior. Our results showed no association between HTR1A and suicidal behavior. However, more studies assessing different populations, as well as larger samples, are needed.OBJETIVO: É possível que uma disfunção nos receptores 1A de serotonina (HTR1A) desempenhe um papel na origem do comportamento suicida. Estudamos a associação entre um polimorfismo funcional no gene HTR1A e comportamento suicida. MÉTODO: Realizamos uma metanálise de estudos de associação genética já publicados através de uma busca nos banco de dados do Medline, PubMed e Web of Science para identificar uma possível correlação entre o polimorfismo rs6295 e comportamento suicida em diferentes populações. RESULTADOS: Foram selecionados quatro estudos com um total de 957 pacientes com comportamento suicida e 957 controles. O alelo G do polimorfismo rs6295 não pôde ser associado a comportamento suicida (modelo de efeitos aleatórios: OR = 1,08; 95%CI: 0,80-1,45; p(Z) = 0,80) na presença de heterogeneidade (Q = 17,84, df = 4, p = 0,0013). Em uma segunda análise, sem heterogeneidade, também foi observada uma associação negativa (OR = 0,94; 95%CI: 0,79-1,13; p(Z) = 0,99). CONCLUSÃO: Pelo que nos consta, trata-se da primeira metanálise cujo objetivo é identificar uma correlação entre o polimorfismo rs6295 do HTR1A e comportamento suicida. Os nossos resultados não demonstraram existir uma correlação entre o HTR1A e comportamento suicida. No entanto, são necessários estudos adicionais que incluam outras populações, assim como amostras maiores.
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- 2012
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41. Influência da interação entre qualidade ambiental e o SNP T102C do gene HTR2A sobre a suscetibilidade à fibromialgia Influence of the interaction between environmental quality and T102C SNP in the HTR2A gene on fibromyalgia susceptibility
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Michelle Mergener, Roze Mary Ribas Becker, Adriana Freitag dos Santos, Geraldine Alves dos Santos, and Fabiana Michelsen de Andrade
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qualidade de vida ,meio ambiente ,serotonina ,polimorfismo genético ,fibromialgia ,quality of life ,environment ,serotonin ,genetic polymorphism ,fibromyalgia ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
OBJETIVO: Investigar a influência genética da variante T102C do gene do receptor 2A de serotonina (HTR2A) e sua interação com aspectos do meio ambiente, como exposição a ruídos, trânsito, clima, oportunidades de adquirir novas informações, segurança física e proteção, dentre outras, como possíveis fatores de risco para o desenvolvimento da síndrome da fibromialgia (SFM). MÉTODOS: Foram avaliados 41 pacientes com SFM e 49 indivíduos-controle. Os fatores ambientais foram avaliados pela aplicação do domínio V do questionário WHOQOL-100 (OMS). Solicitou-se aos pacientes que as respostas representassem os momentos antes do surgimento dos sintomas. A variante T102C do gene do receptor 2A de serotonina (HTR2A) foi determinada por PCR-RFLP. RESULTADOS: Na amostra de pacientes, o número de portadores do alelo 102C foi maior do que o encontrado na amostra controle (76,5% vs. 50%; P = 0,028). Os escores do domínio V foram menores em pacientes quando comparados aos controles (P < 0,001). O fator "falta de oportunidades de adquirir novas informações e habilidades" elevou em quase 14 vezes a chance de desenvolvimento da síndrome (P = 0,009). "Baixa qualidade de cuidados sociais e de saúde", somada à presença do alelo 102C, elevou em mais de 90 vezes (P = 0,005). Contudo, indivíduos portadores desse mesmo alelo que possuem alta qualidade de cuidados sociais e de saúde não se encontram sob risco de desenvolver a SFM. CONCLUSÕES: Esses dados sugerem que tais fatores podem predispor à SFM, especialmente em portadores do alelo 102C. Entretanto, são necessárias investigações com amostras maiores.OBJECTIVES: This study aimed to investigate the genetic influence of the T102C polymorphism of the 2A serotonin receptor gene (HTR2A) and its interaction with environmental aspects, such as exposure to noise, traffic, climate, and opportunities to acquire new information, physical protection, and security, among others, as possible risk factors for developing fibromyalgia syndrome (FMS). METHODS: Forty-one FMS patients and 49 controls were evaluated. Environmental factors were evaluated by application of the V domain of the WHOQOL-100 questionnaire. Patients were asked that their answers represented only the periods preceding the onset of symptoms. The T102C variant of the HTR2A gene was determined through PCR/RFLP. RESULTS: Among patients, the frequency of carriers of the 102C allele was higher than in controls (76.5% vs. 50%; P = 0.028). The scores of the V domain were lower in patients than in controls, indicating a worst perception of the environmental quality by patients (P < 0.001). The factor "lack of opportunities for acquiring new information and skills" increased the chance of developing FMS by almost 14-fold (P = 0.009). The factor "low quality of social care and health" together with the presence of the 102C allele also increased this chance by more than 90-fold (P = 0.005). However, carriers of the same allele who have high quality social care and health are not at a higher risk to develop FMS. CONCLUSION: These data suggest that these factors may predispose to FMS, especially in carriers of the 102C allele. However, studies with larger samples are required to confirm this hypothesis.
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- 2011
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42. Decision-making impairment in obsessive-compulsive disorder as measured by the Iowa Gambling Task
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Felipe Filardi da Rocha, Nathália Bueno Alvarenga, Leandro Malloy-Diniz, and Humberto Corrêa
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comportamento ,transtorno obsessivo-compulsivo ,cognição ,serotonina ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
OBJECTIVE: This study aims to evaluate the process of decision-making in patients with obsessive-compulsive disorder (OCD) using the Iowa Gambling Task (IGT). In addition, we intend to expand the understanding of clinical and demographic characteristics that influence decision-making. METHOD: Our sample consisted of 214 subjects (107 diagnosed with OCD and 107 healthy controls) who were evaluated on their clinical, demographic and neuropsychological features. Moreover, the Iowa Gambling Task (IGT), a task that detects and measures decision-making impairments, was used. RESULTS: We found that OCD patients performed significantly worse on the IGT. Furthermore, features such as symptoms of anxiety did not influence IGT performance. CONCLUSION: Impaired decision-making seems to be a key feature of OCD. Given that OCD is a complex heterogeneous disorder, homogeneous groups are necessary for an accurate characterization of our findings.
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- 2011
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43. Polymorphisms in the 5-HTR2A gene related to obstructive sleep apnea syndrome Polimorfismos no gene HTR2A relacionados à síndrome da apneia obstrutiva do sono
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Vânia Belintani Piatto, Thiago Bittencourt Ottoni de Carvalho, Nely Silva Aragão De Marchi, Fernando Drimel Molina, and José Victor Maniglia
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apneia do sono tipo obstrutiva ,polimorfismo genético ,receptor 5-ht1a de serotonina ,serotonina ,polymorphism genetic ,receptor serotonin 5-ht2a ,serotonin ,sleep apnea obstructive ,Otorhinolaryngology ,RF1-547 - Abstract
Obstructive sleep apnea syndrome (OSAS) is one of the most complex disorders of sleep; it involves several genetic factors that contribute to the phenotype. Serotonin (5-HT) regulates a variety of visceral and physiological functions, including sleep. Gene 5-HTR2A polymorphisms may change the transcription of several receptors in the serotoninergic system, thereby contributing to OSAS. AIM: To investigate the prevalence of T102C and -1438G/A polymorphisms in the 5-HTR2A gene of patients with and without OSAS . MATERIAL AND METHOD: A molecular study of 100 index-cases and 100 controls of both genders. DNA was extracted from blood leukocytes samples and the regions that enclose both polymorphisms were amplified with PCR-RFLP. STUDY DESIGN: A cross-sectional case study. RESULTS: There was a significant prevalence of males in index cases compared to controls (pA síndrome da apneia obstrutiva do sono (SAOS) é um dos distúrbios mais complexos do sono, envolvendo múltiplos fatores genéticos contribuintes para o fenótipo. A serotonina (5-HT) está envolvida na regulação de uma variedade de funções viscerais e fisiológicas, inclusive o sono. Polimorfismos no gene 5-HTR2A podem alterar a transcrição, afetando o número de receptores do sistema serotoninérgico, contribuindo para a SAOS. OBJETIVO: Investigar a prevalência dos polimorfismos T102C e -1438G/A no gene HTR2A em pacientes com e sem SAOS. MATERIAL E MÉTODO: Estudo molecular em 100 pacientes como casos-índice e em 100 como grupo controle, de ambos os gêneros. O DNA foi extraído de leucócitos de sangue periférico e realizada a amplificação das regiões que abrangem ambos os polimorfismos pelas técnicas da PCR-RFLP. DESENHO DO ESTUDO: Estudo de caso/controle em corte transversal. Resultados: Houve prevalência significativa do gênero masculino nos casos-índice em relação aos controles (p
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- 2011
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44. Long-standing malignant pancreatic carcinoid treated with octreotide Carcinoide pancreático maligno de larga evolución tratado con octeotrida
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M. J. Varas-Lorenzo
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Carcinoide pancreático ,Serotoninoma ,Apudoma o tumor neuroendocrino pancreático ,Serotonina ,Ácido 5-hidroxindolacético (5-HIAA) ,Pancreatic carcinoid ,Apudoma or neuroendocrine pancreatic tumor ,Serotonin ,5-Hydroxyndoleacetic acid (5-HIAA) ,Octreotide ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
A male presented with a metastatic, plasma serotonin-secreting (high 5-HIAA in urine), malignant pancreatic carcinoid with a carcinoid-like syndrome, and was assessed using ultrasounds (US), computerized tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) and Octreoscan; he sequentially received chemotherapy, interferon and octreotide, with long-term, 12-year survival after diagnosis. Given this unusual case, the second reported in our country, the overall literature is reviewed.Se presenta un varón con un carcinoide pancreático maligno, con metástasis, secretor de serotonina plasmática (5-HIAA urinario elevado) con síndrome carcinoide-like, evaluado mediante ecografía (US), tomografía computarizada (TAC), resonancia magnética (RM), ultrasonografía endoscópica (USE) y Octreoscan, tratado con quimioterapia, Interferón y Octeotrida, de forma secuencial, con supervivencia prolongada de 12 años después del diagnóstico. A propósito de este caso inusual, el segundo publicado desde nuestro país, se revisa la literatura mundial.
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- 2010
45. Alterations on monoamines concentration in rat hippocampus produced by lipoic acid Alterações na concentração de monoaminas no hipocampo de ratos produzidas pelo ácido lipóico
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Ítala Mônica de Sales Santos, Rizângela Lyne Mendes de Freitas, Gláucio Barros Saldanha, Adriana da Rocha Tomé, Joaquín Jordán, and Rivelilson Mendes de Freitas
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ácido lipóico ,hipocampo ,dopamina ,norepinefrina ,serotonina ,lipoic acid ,hippocampus ,dopamine ,norepinephrine ,serotonin ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The purposes of the present study were to verify monoamines (dopamine (DA), norepinephrine (NE), serotonin (5-HT)), and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) contents in rat hippocampus after lipoic acid (LA) administration. Wistar rats were treated with 0.9% saline (i.p., control group) and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively). After the treatments all groups were observed for 24 h. The NE and DA levels were increased only in 20 mg/kg dose of LA in rat hippocampus. Serotonin content and in their metabolite 5-HIAA levels was decreased in same dose of LA. On the other hand, in DOPAC and HVA levels did not show any significant change. The alterations in hippocampal monoamines can be suggested as a possible of brain mechanism of action from this antioxidant. The outcome of the study may have therapeutic implications in the treatment of neurodegenerative diseases.O objetivo do presente estudo foi verificar a concentração das monoaminas (dopamina (DA), norepinefrina (NA), serotonina (5-HT)), e seus metabólitos (ácido 3,4-hidroxifenil (DOPAC), ácido homovanílico (HVA) e 5 ácido hydroxiindolacético (5-HIAA)) no hipocampo de ratos após administração do ácido lipóico (AL). Ratos Wistar foram tratados com solução salina 0,9% (i.p., grupo controle) e AL (10, 20 ou 30 mg/kg, i.p., AL10, AL20 e AL30 grupos, respectivamente). Após os tratamentos todos os grupos foram observados durante 24 h. O conteúdo de DA no hipocampo de ratos foi aumentado apenas com AL na dose de 20 mg/kg dose. A concentração de serotonina e do seu metabólito 5-HIAA também foi diminuída com esta dose de AL. Por outro lado, os níveis de DOPAC e de HVA não mostrram nenhuma mudança significativa. As alterações na concentração das monoaminas hipocampais podem ser sugeridas como um possível mecanismo de ação cerebral deste antioxidante. O resultado do estudo pode ter implicações terapêuticas no tratamento de doenças neurodegenerativas.
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- 2010
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46. Neonatal administration of fluoxetine did not alter the anxiety indicators, but decreased the locomotor activity in adult rats in the elevated plus-maze Administração neonatal de fluoxetina não alterou os indicadores de ansiedade, mas diminuiu a atividade locomotora em ratos adultos no labirinto elevado em cruz
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Valdenilson Ribeiro Ribas, Helena Karine Rufino Aniceto, Hugo André de Lima Martins, Ketlin Helenise dos Santos Ribas, Renata de Melo Guerra-Ribas, Simone do Nascimento Fraga, Valéria Ribeiro-Ribas, Célia Maria Mendes Vasconcelos, Marcelo Tavares Viana, and Raul Manhaes-de-Castro
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ansiedade ,labirinto elevado em cruz ,serotonina ,fluoxetina ,neonatal ,anxiety ,plus-maze ,serotonin ,fluoxetine ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The objective of this study was evaluate the anxiety and locomotor activity (LA) in 52 Wistar adult male rats, being 26 treated with fluoxetine (10 mg/Kg - sc) in the neonatal period. These same rats received foot shock (FS) (1.6-mA - 2-s) in the 90th day. The anxiety and LA were appraised by plus-maze. The time spent in the open arms was used as anxiety index and the LA was measured by number of entries in closed arms (NECA) and the total of entries (TE). T-test was used with pO objetivo deste estudo foi avaliar a ansiedade e a atividade locomotora (AL) em 52 ratos Wistar adultos machos, sendo 26 tratados no período neonatal com fluoxetina (10 mg/Kg - sc) e no 90º dia, receberam estímulos elétricos nas patas (1,6-mA-2-s). A ansiedade e a AL foram avaliadas por meio do labirinto elevado em cruz. O tempo de permanência dos animais nos braços abertos (BA) foi utilizado como índice de ansiedade e a AL medida pelo número de entradas nos braços fechados (NEBF) e pelo total de entradas (TE) nos BA e BF. O teste t foi utilizado, com (p
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- 2008
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47. Efeito dos níveis de triptofano digestível em dietas para codornas japonesas em postura Dietary digestible tryptophan levels for Japanese laying quails
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Sandra Regina Freitas Pinheiro, Sergio Luiz de Toledo Barreto, Luiz Fernando Teixeira Albino, Horacio Santiago Rostagno, Regina Tie Umigi, and Claudson Oliveira Brito
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aminoácido ,Coturnix coturnix japonica ,exigência ,serotonina ,amino acids ,requirement ,serotonin ,Animal culture ,SF1-1100 - Abstract
O nível dietético adequado (0,12; 0,16; 0,20; 0,24 e 0,28%) de triptofano digestível foi avaliado em 400 codornas japonesas de 21 a 30 semanas de idade, fase de postura. As codornas foram alojadas em gaiolas de 125 cm²/ave, com peso inicial de 158,50 g e produção média de ovos de 84,50%. O delineamento experimental foi em blocos casualizados, constituído por oito blocos, cinco tratamentos, oito repetições de dez aves/repetição e três períodos experimentais de 21 dias cada. Foram avaliados os parâmetros de desempenho das aves, consumo de ração (g/ave/dia), consumo de triptofano (mg/ave/dia), produção de ovos (%/ave/dia), peso médio dos ovos (g), massa de ovos (kg/ave/dia) e conversão alimentar (kg de ração/kg de ovos e por dúzia de ovos). Somente as variáveis consumo de triptofano e produção de ovos apresentaram efeitos significativos dos níveis de triptofano nas dietas. As respostas de desempenho das codornas, respeitando o ajuste estatístico obtido por meio de modelos de regressão linear e do modelo descontínuo LRP, e a interpretação biológica permitem concluir que, para se obter o melhor desempenho produtivo, as dietas de codornas devem conter o nível de 0,21% de triptofano digestível, o que resulta no consumo diário de 45,0 mg/ave de triptofano, correspondendo à relação triptofano: lisina digestível de 21%.The adequate level (0.12, 0.16, 0.20, 0.24, and 0.28%) of the dietary digestible tryptophan was evaluated in 400 laying Japanese quail from 21 to 30 weeks old. The animals were housed in laying cages, with initial weight of 158.50 g and egg production average of 84.50%. A completely randomized blocks design, with eight blocks, five diets, eight replicates of ten birds per replicate and three experimental periods of 21 days each was used. Feed intake (g/bird/day), digestible tryptophan intake (mg/bird/day), egg production (%/bird/day), egg weight (g), egg mass (kg/bird/day) and feed conversion (kg feed intake per kg eggs and dozen eggs) were the characteristics evaluated. Only the characteristics digestible tryptophan intake and egg production rate show significant effects of digestible tryptophan levels in the diets. Performance response of the Japanese quails in posture, regarding the adjustment obtained through models of linear regression and broken-line regression model, and the biological interpretation, allow to conclude that to obtain the best productive performance, the Japanese quails diets should contain the level of 0.21% digestible tryptophan, that results in a daily intake of 45.0 mg/ bird of digestible tryptophan, corresponding to the digestible tryptophan: digestible lysine ratio of 21%.
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- 2008
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48. Neonatal exposure to citalopram, a serotonin selective reuptake inhibitor, programs a delay in the reflex ontogeny in rats Exposição neonatal ao citalopram, um inibidor seletivo da recaptação de serotonina, programa retardo na ontogênese reflexa em ratos
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Teresa Cristina Bomfim de Jesus Deiró, Judelita Carvalho, Elizabeth do Nascimento, Jaiza Maria Barreto Medeiros, Fabiana Cajuhi, Kelli Nogueira Ferraz-Pereira, and Raul Manhães-de-Castro
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serotonina ,programação ,ISRS ,citalopram ,desenvolvimento reflexo ,serotonin ,programming ,SSRI ,reflex development ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Serotonin influences the growth and development of the nervous system, as well as its behavioral manifestations. The possibility exists that increased brain serotonin availability in young animals modulates their neuro-behavioral responses. This study investigated the body weight gain and reflex ontogeny of neonatal rats treated during the suckling period with two doses of citalopram (5 mg, or 10 mg/kg, sc, daily). The time of the appearance of reflexes (palm grasp righting, free-fall righting, vibrissa placing, auditory startle response, negative geotaxis and cliff avoidance) as well as the body weight evolution were recorded. In general, a delay in the time of reflex development and a reduced weight gain were observed in drug-treated animals. These findings suggest that serotoninergic mechanisms play a role in modulating body weight gain and the maturation of most reflex responses during the perinatal period in rats.A serotonina influencia o crescimento e o desenvolvimento do sistema nervoso e sua expressão comportamental. O aumento da disponibilidade de serotonina no cérebro de ratos jovens parece modular as respostas neurocomportamentais. Neste estudo, foram investigados o ganho de peso corporal e a ontogênese dos reflexos em ratos neonatos, tratados diariamente, durante o período de aleitamento, com duas doses de citalopram (5 ou 10 mg/Kg de peso corporal, via subcutânea). Foram avaliados, o tempo de aparecimento dos reflexos (preensão palmar, endireitamento, colocação pelas vibrissas, resposta ao susto, geotáxico negativo e aversão ao precipício), e a evolução do peso corporal. Foi observado atraso no tempo de desenvolvimento de alguns reflexos e redução no ganho de peso corporal. Os achados em ratos sugerem que as alterações no ganho de peso corporal e na maturação dos reflexos são programadas, durante o período perinatal, com participação de mecanismos serotoninérgicos de modulação.
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- 2008
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49. Suppression of Machado-Joseph disease pathogenesis by serotonergic signalling: the contribution of serotonin receptors
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Sousa, Joana Catarina Pereira de, Castro, Andreia Cristiana Teixeira, Pinto, Luísa Alexandra Meireles, and Universidade do Minho
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ISRS ,SCA3 ,Ciências Médicas::Ciências da Saúde ,serotonina ,receptores serotoninérgicos ,serotonin receptors ,C. elegans ,SSRI ,serotonin - Abstract
Tese de Doutoramento em Ciências da Saúde, A doença de Machado-Joseph (DMJ) é uma doença debilitante caracterizada pela perda progressiva do equilíbrio e da coordenação motora. A nível molecular, a DMJ está associada à expansão da repetição de Citosina-Adenina-Guanina (CAG) no gene da ataxina-3. Isto traduz-se num segmento expandido de poliglutaminas na proteína ataxina-3 (ATXN3), que é propenso à auto-associação, sendo a agregação desta proteína uma característica da doença. Apesar dos vários esforços efectuados, não existe cura para esta doença fatal. A modulação da sinalização serotoninérgica foi anteriormente descrita como potencial estratégia terapêutica para a DMJ. O tratamento com citalopram (CIT), um inibidor seletivo da recaptação de serotonina, suprimiu a patogénese da DMJ em vários modelos animais, sendo o efeito do CIT dependente do transportador de serotonina, o seu alvo molecular, com provável contribuição dos receptores serotoninérgicos 5-HT1A/SER-4 e 5-HT2/SER-1. No entanto, o papel de cada receptor serotoninérgico na supressão da proteotoxicidade da ATXN3 mutante não foi ainda elucidado. Aqui, com o objetivo de determinar a contribuição de cada receptor de serotonina (5-HTR) na supressão da proteotoxicidade da ATXN3 usámos um modelo de C. elegans que recapitula as principais características da DMJ, seguindo abordagens químico-genéticas, farmacológicas e bioquímicas, bem como técnicas de microscopia in vivo. Inicialmente, explorámos a contribuição do receptor 5-HT1A usando befiradol, um agonista potente e altamente específico destes receptores. A administração crónica e aguda deste composto melhorou a função motora dos mutantes, sendo o ortólogo do receptor 5-HT1A no nematode, o SER-4, necessário para a sua ação. De forma a aprofundar o conhecimento sobre o impacto do tratamento com befiradol na proteotoxicidade da ATXN3, optimizámos ensaios de retardação em filtro e fracionamento bioquímico para avaliar as espécies agregadas da ATXN3, demonstrando-se que ambas as modalidades de tratamento afectaram a solubilidade desta proteína. De realçar que, usando químicogenética e medições de atividade neuronal, foi-nos possível definir os auto- e hetero-receptores 5- HT1A/SER-4 como essenciais para o efeito terapêutico do befiradol e propor o receptor 5-HT1A como novo alvo terapêutico para a DMJ. Além disso, identificámos uma contribuição parcial dos receptores 5- HT6/SER-5 e 5-HT7/SER-7 para a ação do CIT. Surpreendentemente, o antagonismo dos receptores 5- HT2/SER-1, 5-HT6/SER-5 e 5-HT7/SER-7 mostrou-se benéfico para a função motora de animais mutantes, o que é consistente com dados de perfil de expressão de RNA e farmacoterapia multimodal obtidos no nosso laboratório. Embora promissores, são necessários mais estudos para reforçar estes achados e elucidar as vias específicas pelas quais cada 5-HTR individual afecta a proteotoxicidade da ATXN3., Machado-Joseph disease (MJD) is a debilitating disease mainly characterized by a progressive loss of balance and motor coordination. At the molecular level, this autosomal dominant disease is associated with an expansion of the Cytosine-Adenine-Guanine (CAG) repeat in the ataxin-3 gene. This translates into a pathologic polyglutamine tract in the ataxin-3 protein (ATXN3) that is prone to selfassociate, aggregation of ATXN3 being a hallmark of the disease. Although several efforts have been made, no cure is yet available for this fatal disorder. Serotonergic signalling modulation, by selective serotonin reuptake inhibitors (SSRIs), was previously described as a potential therapeutical strategy for MJD. Treatment with citalopram (CIT), a SSRI used in the clinics to treat depression, suppressed MJD pathogenesis in a disease-modifying manner, in several animal models. CIT’s effect was dependent on its molecular target, the serotonin transporter SERT, likely with the additional need of the serotonin receptors 5-HT1AR/SER-4 and 2-HT2R/SER-1. However, the exact role of each serotonin receptor (5-HTR) in the suppression of mutant ATXN3 proteotoxicity remains to be fully elucidated. Here, we aimed at determining the contribution of each of the 5-HTRs in the suppression of ATXN3 proteotoxicity using a C. elegans model that recapitulates major hallmarks of MJD, by employing chemical genetics, pharmacological- and biochemical- approaches, as well as in vivo dynamic imaging techniques. First, we explored the contribution of the 5-HT1AR using a highly specific and potent agonist of these receptors, befiradol. Chronic and acute administration of befiradol rescued the motor function of mutant animals, the 5-HT1AR orthologue in the nematode, SER-4, being required for its action. To further explore the impact of befiradol treatment in ATXN3 proteotoxicity, we optimised filter retardation and biochemical fractionation assays to assess mutant ATXN3 aggregation states, and we showed that both treatment modalities impacted ATXN3 solubility. Importantly, using chemical genetics and single neuron neuronal activity measurements, we defined 5-HT1AR/SER-4 auto- and heteroreceptors’ function to be essential to befiradol therapeutic outcome, and the 5-HT1AR as a novel therapeutic target for MJD. Additionally, we found a partial contribution of 5-HT6R/SER-5 and 5-HT7R/SER-7 for CIT action and, surprisingly, antagonism of 5-HT2R/SER-1, 5-HT6R/SER-5 and 5-HT7R/SER-7 showed to be beneficial for motor function of mutant animals, which is consistent with RNA-expression profiling and multimodal pharmacotherapy results obtained in our laboratory. Although promising, further studies are needed to support these findings and to elucidate the specific pathways by which each individual serotonin receptor impacts ATXN3 proteotoxicity., The work presented in this thesis was performed at the Life and Health Sciences Research Institute (ICVS) and at the Bn’ML – Behavioral & Molecular Lab, at the School of Medicine, University of Minho. Financial support was provided by grants from the Portuguese Foundation for Science and Technology (FCT): Doctoral Programme in Applied Health Sciences fellowship (PD/BDE/127834/2016) to J. Pereira-Sousa; and by FEDER, through the Competitiveness Internationalization Operational Programme (POCI) under the scope of the project POCI-01-0145-FEDER-031987 to A. Teixeira-Castro, supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER022122); and by National funds, through the FCT - project UIDB/50026/2020 and UIDP/50026/2020. This work was also funded through the National Ataxia Foundation (NAF), USA.
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- 2021
50. Effects of serotonin transporter and receptor polymorphisms on depression.
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López-Echeverri YP, Cardona-Londoño KJ, Garcia-Aguirre JF, and Orrego-Cardozo M
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- Humans, Polymorphism, Genetic, Serotonin genetics, Alleles, Serotonin Plasma Membrane Transport Proteins genetics, Depression genetics
- Abstract
Introduction: Serotonin is highly implicated in the regulation of emotional state and the execution of cognitive tasks, so much so that the serotonin transporter genes (5-HTT, SLC6A4) and the serotonin receptor genes (HTR1A, HTR1B, HTR2A) have become the perfect candidates when studying the effects that these genes and their polymorphic variations have on depression characteristics., Objective: A review of research reports that have studied the effects of variations in the serotonin transporter and receptor genes on different clinical features of depression., Methods: A search of the Scopus, Web of Science and PubMed databases was conducted using the keywords ("depression" AND "polymorphism")., Conclusions: According to the review of 54 articles, the short allele of the 5-HTTLPR polymorphism was found to be the most reported risk factor related to the development of depression and its severity. Variations in the genes studied (SLC6A4, HTR1A, HTR2A) can generate morphological alterations of brain structures., (Copyright © 2021 Asociación Colombiana de Psiquiatría. Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2023
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