21 results on '"Bellini, María José"'
Search Results
2. IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
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Falomir-Lockhart, Eugenia, Dolcetti, Franco Juan Cruz, Herrera, Macarena Lorena, Pennini, Jerónimo, Zappa Villar, María Florencia, Salinas, Gabriela, Portiansky, Enrique, Spittau, Björn, Lacunza, Ezequiel, Hereñú, Claudia Beatriz, and Bellini, María José
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- 2022
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3. Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice
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Diz-Chaves, Yolanda, Astiz, Mariana, Bellini, Maria José, and Garcia-Segura, Luis M.
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- 2013
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4. IGF-1 GENE THERAPY ON GLIA CELLS AND DOPAMINERGIC NEURONS INTERACTION IN NEURODEGENERATIVE MODELS
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Champarini, Leandro, Basmadjian, Osvaldo, Bellini, María José, and Hereñú, Claudia
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- 2023
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5. Estradiol Decreases Cortical Reactive Astrogliosis after Brain Injury by a Mechanism Involving Cannabinoid Receptors
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López Rodríguez, Ana Belén, Mateos Vicente, Beatriz, Romero-Zerbo, Silvana Y., Rodriguez-Rodriguez, Noé, Bellini, María José, Rodriguez de Fonseca, Fernando, Bermudez-Silva, Francisco Javier, Azcoitia, Iñigo, Garcia-Segura, Luis M., and Viveros, María-Paz
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- 2011
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6. Implication of Oxidative Stress, Aging, and Inflammatory Processes in Neurodegenerative Diseases: Growth Factors as Therapeutic Approach
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Herrera, Macarena Lorena, Falomir Lockhart, Eugenia, Dolcetti, Franco Juan Cruz, Arnal, Nathalie, Bellini, María José, Hereñú, Claudia Beatriz, Gargiulo, Pascual Ángel, and Mesones Arroyo, Humberto Luis
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Neurodegeneración ,Especies reactivas del oxígeno ,Ciencias Médicas ,Estrés oxidativo - Abstract
Oxidative stress (OS) is defined as the imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system. Living organisms produce ROS from molecular oxygen as a consequence of normal cellular metabolism. In order to prevent damage, cells have an antioxidant defense system constituted by an enzymatic component (including catalases, superoxide dismutases, etc.) and nonenzymatic antioxidants component (glutathione, α-tocopherol, ascorbic acid, etc.). When the levels of ROS exceed cell capacity, it can cause damage in cellular components such as carbohydrates, nucleic acids, lipids, and proteins, thus altering their function. Whenever this imbalance occurs within the central nervous system, it can lead to the development of the neurodegenerative disorders. Neurodegenerative diseases are characterized by the loss of neuronal cells and, in most cases, by the aggregates of proteins that form intracytoplasmic and intranuclear inclusions in neurons and glial cells. Data on the literature show that there are two possible mechanisms involved in most of neurodegenerative diseases: (1) mutations and/or aggregation of characteristic proteins of each disease such as α-synuclein in Parkinson’s disease (PD) or beta-amyloid peptide in Alzheimer’s disease (AD) and (2) dysfunction of mitochondrial energy metabolism in neurons. In this section, we will focus on this last one., Instituto de Investigaciones Bioquímicas de La Plata
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- 2019
7. Synergistic interaction between Cu overload and Aβ peptide promotes pro‐inflammatory response of microglia.
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Zubillaga, Marlene, Calaf, Xenia Abadin, Colell, Anna, Bellini, María José, and Arnal, Nathalie
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Background: Changes in copper (Cu) homeostasis have been consistently linked to Alzheimer's disease (AD). Cu can bind to amyloid beta (Ab) and enhance neurotoxicity through the generation of reactive oxygen species.Furthermore, Cu possesses both pro‐ and anti‐inflammatory properties mediated by its proximity to amyloid plaques. A key pro‐inflammatory pathway reported induced in AD is the NLRP3 inflammasome that leads to the activation of inflammatory caspases, mainly caspase‐1, and the processing of interleukin‐1b (IL‐1b) into its active form. This work aimed to assess the synergistic interaction between Cu overload and the Aβ‐induced inflammatory response on microglia and evaluate the underlying mechanisms. Method: Using immortalized mouse microglia (SIM‐A9) exposed to 1 uM Ab and subtoxic doses of Cu (50, 100 and 200 uM) for 24 h, we assessed ROS by fluorometry using Dihydroethidium (DHE), expression levels of inflammasome‐related proteins by western blot and RT‐PCR selfie, and phagocytosis of microglia by confocal microscopy using fluorescent microbeads (1µm). To assess inflammasome assembly, cells were transfected with the pLEX‐MSC‐ASC‐GFP vector and ASC speckle formation was analyzed by confocal microscopy. Results: Cu treatment induced IL‐1b and Nlrp3 expression, which was further enhanced when combined with Aβ. While untreated cells showed homogeneously distributed ASCs in the cytosol, we found "speckles" of ASCs in those treated with Cu and Cu plus Aβ, in the vicinity of the nucleus, indicating involvement of the inflammasome. Cu treatment increased total cholesterol (Cho) and mitochondrial Cho levels and was accompanied by a significant decrease in mitochondrial GSH levels. Accordingly, ROS levels increased significantly with the combination of Cu and Aβ. Oxidative stress was prevented by glutathione ester (GSHee) treatment and the use of mitochondrial antioxidant agents (MitoTEMPO and MitoQ). In parallel, we analyzed microglia phagocytosis by confocal microscopy. Microbead uptake was significantly impaired after Cu overload but was partially restored by pretreatment with GSHee, which recovered mitochondrial GSH and reduced oxidative stress Conclusion: High Cu levels regulate the microglial response to Aβ by boosting mitochondrial oxidative stress, resulting in inflammasome activation with the release of pro‐inflammatory cytokines such as IL‐1b) and decreased phagocytic capacity, which may contribute to the accumulation and formation of Aβ deposits. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Sex frailty differences in ageing mice: Neuropathologies and therapeutic projections.
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Herrera, Macarena Lorena, Basmadjian, Osvaldo Martin, Falomir‐Lockhart, Eugenia, Dolcetti, Franco Juan‐Cruz, Hereñú, Claudia Beatriz, and Bellini, María José
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SOMATOMEDIN C ,AGE differences ,MICE - Abstract
It is well‐established that females live longer than males. Paradoxically, women tend to have poorer health, a condition often named sex frailty. The aim of this study was to evaluate possible frailty predictors in older mice in a sex‐specific manner, in order to employ these predictors to follow‐up therapy efficiency. To further evaluate therapy effects, we also investigated the use of neurotrophic insulin‐like growth factor 1 (IGF‐1) gene therapy and its correlation with the expression of this frailty and emotional behaviour. In order to evaluate frailty, we employed two different approaches. We performed a frailty assessment through a 31‐Item Clinical Frailty Index and through a Performance‐Based 8‐Item Frailty Index. Our results show that both indexes are in concordance to evaluate sex differences, but they do not correlate when evaluating IGF‐1 therapy effects. Moreover, in order to reduce test‐to‐test variability for measures of dependent variables, we compared open field results across studies assessing sex and treatment by means of the z‐score normalization. The data show that regular open field parameters submitted to z‐score normalization analysis could be a useful tool to identify sex differences in ageing mice after growth factor therapies. Taking this into account, sex is a factor that influences the incidence and/or nature of all major complex diseases; the main outcome of our investigation is the development of an efficient tool that compares the use of different frailty index calculations. This represents an important strategy in order to identify sex differences and therapy efficiency in ageing models. [ABSTRACT FROM AUTHOR]
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- 2020
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9. Restauration of age related motor impairment: role of IGF-1 based gene therapy and microglial activation
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Falomir Lockhart, Eugenia, Millan, J., Anesetti Nelli, S., Hereñú, Claudia Beatriz, and Bellini, María José
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nervous system ,Ciencias Médicas ,Microglía - Abstract
In the current study we implemented ICV IGF-1 gene therapy in very old rats (28 months) and assessed the motor performance pre and 17-days after surgery. Glial immunoreactivity in striatum was evaluated by Iba1 and GFAP markers., Facultad de Ciencias Médicas
- Published
- 2015
10. Estrogen actions on glial reactivity and inflammation-mediated memory impairment: sex differences and interaction with other neurotrophic factors
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Bellini, María José and González Burgos, Ignacio
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cognition ,sex differences ,inflammation ,glia ,Biología ,estrogen - Abstract
There is growing evidence that documents profound effects of estrogens on learning, memory, and mood as well as neurodevelopment and neurodegenerative diseases. However, the ability of estradiol to influence synaptic plasticity, neurotransmission, neurodegeneration and cognition, could be different depending on sex dimorphisms. It emerges that estrogens have different, even opposite, effects as well as similar effects in male and female brains. The protective effects of estradiol on neural cells are mediated in part by modulation of neurotrophic factors such as insulin like growth factor (IGF-l), tyrosine kinase A (Trk A), nerve growth factors (NGF), and the like. Also, it modulates the action of neurotrophins, which in turn regulate the synaptogenesis, synaptic plasticity and synaptic functions. By these actions estrogen prevents or slows down the neurodegenerative process. Another described effect of estradiol is the capacity to modulate inflammatory response mediated by glial cells. Neuroinflammation is a feature not only of many neurological disorders but also of aging, and it is accompanied by activation of glial cells and the release of proinflammatory cytokines and chemokines. Such activation is a normal response oriented to protect neural tissue. However, excessive and chronic activation of glia may lead to neurotoxicity and may be harmful for neural tissue. Estrogenic compounds may be candidates to counteract brain inflammation under neurodegenerative conditions by targeting the production and release of proinflammatory molecules by glial cells. In this chapter we will review different mechanisms that may be implicated in the diverse actions of estradiol, the differences according to gender and we empathize in the anti-inflammatory action on glial cell. We will also explore the interaction of estradiol with others neurotrophic factors, such as IGF-I in the regulation of neurodegeneration and memory impairment. Finally, the possibility of using selective estrogen receptor modulators (SERMs) to exert estradiollike neuroprotective actions in the brain as an alternative to estrogen will be discussed. Instituto de Investigaciones Bioquímicas de La Plata
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- 2015
11. Neuroprotective gene therapy in the aging brain
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Pardo, Joaquín, Morel, Gustavo Ramón, Pereyra, Andrea Soledad, López León, Micaela, Brown, Oscar Alfredo, Bellini, María José, Goya, Rodolfo Gustavo, and González Burgos, Ignacio
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Enfermedad de Alzheimer ,Ciencias Médicas ,Envejecimiento ,Terapia génica - Abstract
Aging is associated with a progressive increase in the incidence of neurodegenerative diseases in both laboratory animals and humans. In the central nervous system, cholinergic and dopaminergic (DA) neurons are among the cells most susceptible to the deleterious effects of age. Thus, the basal forebrain cholinergic system is known to undergo moderate neurodegenerative changes during normal aging as well as severe atrophy in Alzheimer’s disease (AD). Parkinson's disease (PD), a degeneration of nigro-striatal DA neurons is the most conspicuous reflection of the vulnerability of DA neurons to age. Overall, there is growing evidence that a progressive decline in cognitive function and central DA activity represents basic features of normal aging both in humans and laboratory rodents. Exacerbation of these processes contributes to the symptoms of AD and PD, respectively. In this context, neurotrophic factors that can prevent or delay the decline in cognitive function and central DA activity during normal aging may reveal new therapeutic avenues for treatment of AD and PD and are therefore of clinical interest. Among the peptide factors, Insulin-like Growth Factor I (IGF-I) and Glial cell line-Derived Neurotrophic Factor are emerging as powerful neuroprotective molecules for the treatment of neurodegenerative pathologies. Among the neurosteroids, estrogens are recognized as neuroprotective and seem to act synergistically with IGF-I and possibly other neurotrophic peptides. This chapter will discuss the evidence supporting the neuroprotective relevance of the above factors., Instituto de Investigaciones Bioquímicas de La Plata
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- 2014
12. Aldehyde dehydrogenase 2 in the spotlight: The link between mitochondria and neurodegeneration.
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Deza-Ponzio, Romina, Herrera, Macarena Lorena, Bellini, María José, Virgolini, Miriam Beatriz, and Hereñú, Claudia Beatriz
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- 2018
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13. Selective oestrogen receptor modulators decrease the inflammatory response of glial cells
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Arévalo, María Ángeles, Diz-Chaves, Yolanda, Santos-Galindo, María, Bellini, María José, and García-Segura, Luis M.
- Abstract
Neuroinflammation comprises a feature of many neurological disorders that is accompanied by the activation of glial cells and the release of pro-inflammatory cytokines and chemokines. Such activation is a normal response oriented to protect neural tissue and it is mainly regulated by microglia and astroglia. However, excessive and chronic activation of glia may lead to neurotoxicity and may be harmful for neural tissue. The ovarian hormone oestradiol exerts protective actions in the central nervous system that, at least in part, are mediated by a reduction of reactive gliosis. Several selective oestrogen receptor modulators may also exert neuroprotective effects by controlling glial inflammatory responses. Thus, tamoxifen and raloxifene decrease the inflammatory response caused by lipopolysaccharide, a bacterial endotoxin, in mouse and rat microglia cells in vitro. Tamoxifen and raloxifene are also able to reduce microglia activation in the brain of male and female rats in vivo after the peripheral administration of lipopolysaccharide. In addition, tamoxifen decreases the microglia inflammatory response induced by irradiation. Furthermore, treatment with tamoxifen and raloxifene resulted in a significant reduction of the number of reactive astrocytes in the hippocampus of young, middle-aged and older female rats after a stab wound injury. Tamoxifen, raloxifene and the new selective oestrogen receptor modulators ospemifene and bazedoxifene decrease the expression and release of interleukine-6 and interferon-γ inducible protein-10 in cultured astrocytes exposed to lipopolysaccharide. Ospemifene and bazedoxifene exert anti-inflammatory effects in astrocytes by a mechanism involving classical oestrogen receptors and the inhibition of nuclear factor-kappa B p65 transactivation. These data suggest that oestrogenic compounds are candidates to counteract brain inflammation under neurodegenerative conditions by targeting the production and release of pro-inflammatory molecules by glial cells. © 2011 Blackwell Publishing Ltd.
- Published
- 2012
14. Prolactin and thyroid hormones in dogs
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Castillo, Víctor Alejandro, Lalia, J., Scodellaro, Carla Floriana, Bellini, María José, and Gobello, María Cristina
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endocrine system ,enfermedad endocrina ,endocrine system diseases ,Ciencias Veterinarias ,prolactina ,canino ,glándula tiroidea ,hipotiroidismo ,Hormonas ,prolactin ,canine ,thyroid gland ,hypothyroidism ,Perros ,hormones, hormone substitutes, and hormone antagonists - Abstract
Muy poco se conoce sobre la concentración sérica de prolactina (PRL) bajo condiciones patológicas en perros. Para describir la relación entre las concentraciones séricas de PRL y las hormonas tiroideas se usaron cuarenta y cinco perros machos y hembras de raza pura y mestizos con sospecha clínica de hipotiroidismo, de los cuales se tomaron muestras de sangre para determinaciones séricas de PRL y tirotrofina (TSH), tiroxina (T4) y/o T4 libre (T4L). Las concentraciones de PRL en perros hipotiroideos y eutiroideos se compararon con el test de Mann-Whitney. Para la descripción adicional de los datos se correlacionó la PRL y la TSH, T4L o T4. El porcentaje cambio de la PRL se calculó en los pacientes en los que se realizó la prueba de estimulación con TRH. La concentracion sérica de PRL de la totalidad de los perros hipotiroideos (n= 34) y eutiroideos (n= 11) fue de 25.9±4.8 y 14.6±6.5 ng/ml, respectivamente (p >0.05). No se encontraron diferencias significativas entre la PRL y las diferentes hormonas tiroideas en ninguno de los grupos. El perro estimulado se clasificó como hipotiroideo subclínico (grado I). En ese animal la prolactina aumentó 5 veces (de 0.4 a 2.1 ng/ml) después de la inyección de TRH. Deben realizarse trabajos adicionales para describir la prolactinemia en caninos con hipotiroidismo., There is very scarce information concerning prolactin (PRL) serum concentrations under pathologic conditions in dogs. To describe the relationship between PRL and thyroid hormones serum concentrations forty-five cross- and pure-bred male and female dogs with clinical suspicious of hypothyroidism were blood sampled for PRL and thyrotropin (TSH), thyroxin (T4) and/or free T4 (FT4) serum determinations. Prolactin concentrations in hypothyroid and euthyroid dogs were compared by the Mann-Whitney test. For further description of data correlation analyses between PRL and TSH, FT4 or T4 were also tested. Percentage PRL change was calculated in the patient in which the TRH stimulation test was carried out. Overall serum PRL concentrations in hypothyroid (n= 34) and euthyroid (n= 11) dogs were 25.9±4.8 and 14.6±6.5 ng/ml, respectively (p >0.05). No significant correlation could be found between PRL and the different thyroid hormones in any group. The stimulated dog was classified as subclinical a hypothyroid (grade I). Prolactin increased 5 times (from 0.4 to 2.1 ng/ ml) after TRH injection in this animal. Further work should be done to describe prolactinemia in canine hypothyroidism., Facultad de Ciencias Veterinarias
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- 2010
15. The thymus-neuroendocrine axis: physiology, molecular biology, and therapeutic potential of the thymic peptide thymulin
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Reggiani, Paula Cecilia, Morel, Gustavo Ramón, Console de Avegliano, Gloria Miriam, Barbeito, Claudio Gustavo, Rodríguez, Silvia Susana, Brown, Oscar Alfredo, Bellini, María José, Pleau, Jean-Marie, Dardenne, Mireille, and Goya, Rodolfo Gustavo
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Thymulin ,Gene therapy ,Ovarian dysgenesis ,Artificial gene ,Ciencias Médicas ,Antiinflammatory ,Hypophysiotropic activity ,Neuroendocrine control - Abstract
Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to the molecule. After its discovery in the early 1970s, thymulin was characterized as a thymic hormone involved in several aspects of intrathymic and extrathymic T cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysotropic peptide. In recent years, interest has arisen in the potential use of thymulin as a therapeutic agent. Thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. Furthermore, an adenoviral vector harboring a synthetic gene for thymulin, stereotaxically injected in the rat brain, achieved a much longer expression than the adenovirally mediated expression in the brain of other genes, thus suggesting that an anti-inflammatory activity of thymulin prevents the immune system from destroying virus-transduced brain cells. Other studies suggest that thymulin gene therapy may also be a suitable therapeutic strategy to prevent some of the endocrine and metabolic alterations that typically appear in thymus-deficient animal models. The present article briefly reviews the literature on the physiology, molecular biology, and therapeutic potential of thymulin., Instituto de Investigaciones Bioquímicas de La Plata, Facultad de Ciencias Veterinarias, Comisión de Investigaciones Científicas de la provincia de Buenos Aires
- Published
- 2009
16. Gene Therapy in the Neuroendocrine System
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Hereñú, Claudia Beatriz, Morel, Gustavo Ramón, Bellini, María José, Reggiani, Paula Cecilia, Sosa, Yolanda Elena, Brown, Oscar Alfredo, Goya, Rodolfo Gustavo, Arzt, Eduardo, Bronstein, Marcello, and Guitelman, Mirtha
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Biología ,hormones, hormone substitutes, and hormone antagonists - Abstract
The implementation of experimental gene therapy in animal models of neuroendocrine diseases is an area of growing interest. In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, and in Koletsky (fak/fak) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively, were stereotaxically injected in the relevant hypothalamic regions. In rats, aging brings about a progressive degeneration and loss of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons, which are involved in the tonic inhibitory control of prolactin secretion and lactotropic cell proliferation. Stereotaxic injection of an adenoviral vector expressing insulin-like growth factor I corrected their chronic hyperprolactinemia and restored TIDA neuron numbers. Spontaneous intermediate lobe pituitary tumors in a retinoblastoma (Rb) gene mutant mouse were corrected by injection of an adenoviral vector expressing the human Rb cDNA and experimental prolactinomas in rats were partially reduced by intrapituitary injection of an adenoviral vector expressing the HSV1-thymidine kinase suicide gene. These results suggest that further implementation of gene therapy strategies in neuroendocrine models may be highly rewarding. Instituto de Investigaciones Bioquímicas de La Plata
- Published
- 2006
17. Influence on effectiveness of early treatment with anti-TNF therapy in rheumatoid arthritis.
- Author
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Escudero-Vilaplana V, Ramírez-Herraiz E, Trovato-López N, Alañón-Plaza E, Bellini MJ, Herranz-Alonso A, Bellón-Cano JM, Morell-Baladrón A, Sanjurjo-Sáez M, Escudero-Vilaplana, Vicente, Ramírez-Herraiz, Esther, Trovato-López, Nicolás, Alañón-Plaza, Estefanía, Bellini, María José, Herranz-Alonso, Ana, Bellón-Cano, José María, Morell-Baladrón, Alberto, and Sanjurjo-Sáez, María
- Published
- 2012
18. Editorial: Modulating Glial Cells Phenotype: New Findings and Therapies.
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Bellini, María José, Diz-Chaves, Yolanda, and Ramos, Alberto Javier
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NEUROGLIA ,MICROGLIA ,PHENOTYPES ,PATHOLOGY - Published
- 2020
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19. Actions of estrogens on glial cells: Implications for neuroprotection
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Arevalo, María-Angeles, Santos-Galindo, María, Bellini, María-José, Azcoitia, Iñigo, and Garcia-Segura, Luis M.
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NEURODEGENERATION , *NEUROGLIA , *ESTROGEN receptors , *ENCEPHALITIS , *BRAIN injuries , *NEUROPROTECTIVE agents , *OLIGODENDROGLIA - Abstract
Abstract: Glial cells are directly or indirectly affected by estradiol and by different estrogenic compounds, such as selective estrogen receptor modulators. Acting on oligodendrocytes, astrocytes and microglia, estrogens regulate remyelination, edema formation, extracellular glutamate levels and the inflammatory response after brain injury. In addition, estradiol induces the expression and release of growth factors by glial cells that promote neuronal survival. Therefore, glial cells are important players in the neuroprotective and reparative mechanisms of estrogenic compounds. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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20. IGF1 gene therapy in middle-aged female rats delays reproductive senescence through its effects on hypothalamic GnRH and kisspeptin neurons.
- Author
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Dolcetti FJC, Falomir-Lockhart E, Acuña F, Herrera ML, Cervellini S, Barbeito CG, Grassi D, Arevalo MA, and Bellini MJ
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- Female, Rats, Animals, Pituitary Hormone-Releasing Hormones, Insulin-Like Growth Factor I genetics, Hypothalamus, Gonadotropins, Neurons, Aging, Genetic Therapy, Kisspeptins genetics, Gonadotropin-Releasing Hormone genetics
- Abstract
The process of aging is the result of progressive loss of homeostasis and functional body impairment, including the central nervous system, where the hypothalamus plays a key role in regulating aging mechanisms. The consequences of aging include a chronic proinflammatory environment in the hypothalamus that leads to decreased secretion of gonadotropin-releasing hormone (GnRH) and impairs kisspeptin neuron functionality. In this work, we investigated the effect of insulin-like growth factor 1 (IGF1) gene therapy on hypothalamic kisspeptin/GnRH neurons and on microglial cells, that mediate the inflammatory process related with the aging process. The results show that IGF1 rats have higher kisspeptin expression in the anteroventral periventricular (AVPV) nucleus and higher immunoreactivity of GnRH in the arcuate nucleus and median eminence. In addition, IGF1-treated animals exhibit increased numbers of Iba1
+ microglial cells and MHCII+ /Iba1+ in the AVPV and arcuate nuclei. In conclusion, IGF1 gene therapy maintains kisspeptin production in the AVPV nucleus, induces GnRH release in the median eminence, and alters the number and reactivity of microglial cells in middle-aged female rats. We suggest that IGF1 gene therapy may have a protective effect against reproductive decline.- Published
- 2022
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21. Novel adenoviral IGF-1 administration modulates the association between depressive symptoms and aging: Does gender matter?
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Herrera ML, Basmadjian OM, Falomir Lockhart E, Dolcetti FJ, Hereñú CB, and Bellini MJ
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- Age Factors, Aging drug effects, Aging physiology, Animals, Female, Insulin-Like Growth Factor I metabolism, Male, Mice, Mice, Inbred C57BL, Models, Animal, Muscle Strength, Sex Factors, Depression drug therapy, Depression physiopathology, Insulin-Like Growth Factor I pharmacology
- Abstract
Depression is an illness of multifactorial origin and it seems to involve the dysregulation of many physiological processes. It also has been associated with age and a decreased in the expression of some neurotrophins. However, there are not unique animal models to assay depressive-like behavior, with male and females responding differently. In this study, we report the effects of gender on aged associated depressive signs as frailty, muscular strength and motor activity, as well as the role of intramuscular IGF-1 gene therapy in these processes. We found that male mice had higher general discomfort than females. Moreover, we observed that IGF-1 treatment did not modify this index in females. Regarding male mice, adenoviral IGF-1 injection reduced frailty scores compared to its adenoviral control. According to data, IGF-1 gene therapy had a positive effect on depressive associated hypo-locomotion activity as indicate by delta of total distance and the increment observed in time of mobility in male mice. This neurotrophic factor also increased the latency of time to fall in grip strength in male mice compared to female mice. Moreover, we observed that, while the therapy had no effect on the digging behavior, IGF-1 treatment diminished the latency to dig and increase the number of buried marbles in male mice, having no effect on female. The present study demonstrates that, in order to establish an animal model of depression both, gender and age are relevant variables/factors to consider. We also conclude that a frailty phenotype underlies depressive-like symptoms in an experimental mouse model. Furthermore, we demonstrated that intramuscular injection represents a less invasive, feasible and controllable route of IGF-1 gene delivery for the treatment of the depressive phenotype in old mice., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
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