18 results on '"Leggieri, Adele"'
Search Results
2. Ankk1 Loss of Function Disrupts Dopaminergic Pathways in Zebrafish.
- Author
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Leggieri, Adele, García-González, Judit, Torres-Perez, Jose V., Havelange, William, Hosseinian, Saeedeh, Mech, Aleksandra M., Keatinge, Marcus, Busch-Nentwich, Elisabeth M., and Brennan, Caroline H.
- Subjects
APOMORPHINE ,KINASES ,RECEPTOR-interacting proteins ,BRACHYDANIO ,CEREBRAL cortex ,DOPAMINE receptors ,DOPAMINE agonists - Abstract
Ankyrin repeat and kinase domain containing 1 (ANKK1) is a member of the receptor-interacting protein serine/threonine kinase family, known to be involved in cell proliferation, differentiation and activation of transcription factors. Genetic variation within the ANKK1 locus is suggested to play a role in vulnerability to addictions. However, ANKK1 mechanism of action is still poorly understood. It has been suggested that ANKK1 may affect the development and/or functioning of dopaminergic pathways. To test this hypothesis, we generated a CRISPR-Cas9 loss of function ankk1 zebrafish line causing a 27 bp insertion that disrupts the ankk1 sequence introducing an early stop codon. We found that ankk1 transcript levels were significantly lower in ankk1 mutant (ankk1
27 ins ) fish compared to their wild type (ankk1+/+ ) siblings. In ankk1+/+ adult zebrafish brain, ankk1 protein was detected in isocortex, hippocampus, basolateral amygdala, mesencephalon, and cerebellum, resembling the mammalian distribution pattern. In contrast, ankk1 protein was reduced in the brain of ankk127 ins/ 27 ins fish. Quantitative polymerase chain reaction analysis revealed an increase in expression of drd2b mRNA in ankk127 ins at both larval and adult stages. In ankk1+/+ adult zebrafish brain, drd2 protein was detected in cerebral cortex, cerebellum, hippocampus, and caudate homolog regions, resembling the pattern in humans. In contrast, drd2 expression was reduced in cortical regions of ankk127 ins/ 27 ins being predominantly found in the hindbrain. No differences in the number of cell bodies or axonal projections detected by anti-tyrosine hydroxylase immunostaining on 3 days post fertilization (dpf) larvae were found. Behavioral analysis revealed altered sensitivity to effects of both amisulpride and apomorphine on locomotion and startle habituation, consistent with a broad loss of both pre and post synaptic receptors. Ankk127 ins mutants showed reduced sensitivity to the effect of the selective dopamine receptor antagonist amisulpride on locomotor responses to acoustic startle and were differentially sensitive to the effects of the non-selective dopamine agonist apomorphine on both locomotion and habituation. Taken together, our findings strengthen the hypothesis of a functional relationship between ANKK1 and DRD2 , supporting a role for ANKK1 in the maintenance and/or functioning of dopaminergic pathways. Further work is needed to disentangle ANKK1 's role at different developmental stages. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
3. Id(entifying) the inhibitor of DNA binding 3 in the brain of Nothobranchius furzeri upon aging.
- Author
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Leggieri, Adele, Palladino, Antonio, Attanasio, Chiara, Avallone, Luigi, Girolamo, Paolo, D'Angelo, Livia, and Lucini, Carla
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AGING , *BASIC proteins , *DNA , *CELL differentiation , *CELL motility - Abstract
Inhibitors of DNA (Id) are key transcription factors (TFs) regulating neurogenic processes. They belong to the helix‐loop‐helix (HLH) TF family and are dominant negative regulators of basic HLH proteins (bHLHs). Specifically, they inhibit cell differentiation and enhance cell proliferation and motility. The Id family includes four members, Id1, Id2, Id3, and Id4, which have been identified in nearly all vertebrates. The transcript catalog of the African turquoise killifish, Nothobranchius furzeri, contains all four TFs and has evolved showing positive selection for Id3. N. furzeri, a teleost, is the short‐lived vertebrate and is gaining increasing scientific interest as a new model organism in aging research. It is characterized by embryonic diapause, explosive sexual maturation, and rapid aging. In this study, we investigated both the expression and the role of Id3 in the brain of this model organism. Interestingly, Id3 was upregulated age‐dependently along with a distribution pattern resembling that of other vertebrates. Additionally, the gene has undergone positive selection during evolution and shows a high degree of conservation relative to that of other vertebrates. These features make N. furzeri a valid tool for aging studies and a potential model in translational research. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Nerve growth factor is expressed and stored in central neurons of adult zebrafish.
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Cacialli, Pietro, Gatta, Claudia, D'Angelo, Livia, Leggieri, Adele, Palladino, Antonio, Girolamo, Paolo, Pellegrini, Elisabeth, and Lucini, Carla
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NERVE growth factor ,NEUROTROPHINS ,NEURAL stem cells ,NEURONS ,CENTRAL nervous system ,NEUROGLIA - Abstract
Nerve growth factor (NGF), a member of the neurotrophin family, was initially described as neuronal survival and growth factor, but successively has emerged as an active mediator in many essential functions in the central nervous system of mammals. NGF is synthesized as a precursor pro‐NGF and is cleaved intracellularly into mature NGF. However, recent evidence demonstrates that pro‐NGF is not a simple inactive precursor, but is also secreted outside the cells and can exert multiple roles. Despite the vast literature present in mammals, studies devoted to NGF in the brain of other vertebrate models are scarce. Zebrafish is a teleost fish widely known for developmental genetic studies and is well established as model for translational neuroscience research. Genomic organization of zebrafish and mouse NGF is highly similar, and zebrafish NGF protein has been reported in mature and two‐precursors forms. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the NGF mRNA and protein distribution in the adult zebrafish brain and to characterize the phenotype of NGF‐positive cells. NGF mRNA was visualized by in situ hybridization on whole‐mount brains. NGF protein distribution was assessed on microtomic sections by using an antiserum against NGF, able to recognize pro‐NGF in adult zebrafish brain as demonstrated also in previous studies. To characterize NGF‐positive cells, anti‐NGF was employed on microtomic slides of aromatase B transgenic zebrafish (where radial glial cells appeared fluorescent) and by means of double‐immunolabeling against NGF/proliferative cell nuclear antigen (PCNA; proliferation marker) and NGF/microtube‐associated protein2 (MAP2; neuronal marker). NGF mRNA and protein were widely distributed in the brain of adult zebrafish, and their pattern of distribution of positive perikaryal was overlapping, both in males and females, with few slight differences. Specifically, the immunoreactivity to the protein was observed in fibers over the entire encephalon. MAP2 immunoreactivity was present in the majority of NGF‐positive cells, throughout the zebrafish brain. PCNA and aromatase B cells were not positive to NGF, but they were closely intermingled with NGF cells. In conclusion, our study demonstrated that mature neurons in the zebrafish brain express NGF mRNA and store pro‐NGF. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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5. The Case Study of Nesfatin-1 in the Pancreas of Tursiops truncatus.
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Gatta, Claudia, De Felice, Elena, D'Angelo, Livia, Maruccio, Lucianna, Leggieri, Adele, Lucini, Carla, Palladino, Antonio, Paolucci, Marina, Scocco, Paola, Varricchio, Ettore, and de Girolamo, Paolo
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APPETITE depressants ,HOMEOSTASIS ,CENTRAL nervous system diseases ,PANCREATIC diseases ,HYPERGLYCEMIA - Abstract
Nesfatin-1 (Nesf-1) is an anorexigenic peptide involved in the regulation of homeostatic feeding. Nesf-1 is expressed in the central nervous system and other organs, including pancreas, where it promotes the release of insulin from β-cells. This raises the possibility that Nesf-1 dysfunction could be involved in metabolic disorders, particularly in type 2 diabetes mellitus (T2D). Recently, it has been discovered that dolphins can be a natural animal model that fully replicates human T2D, due to its prolonged glucose tolerance curve and maintenance of a state of hyperglycemia similar to human T2D during fasting. This correspondence suggests that dolphins may be a suitable model for investigating physiological and pathological metabolic disorders. Here, we have characterized Nesf-1 distribution in the pancreas of the common bottlenose dolphin (Tursiops truncatus) and measured plasmatic levels of Nesf-1 and glucose during fasting and post-prandial states. The Mediterranean Marine Mammal Tissue Bank (MMMTB) of the University of Padova provided us with pancreas samples, derived from four animals, and plasma samples, collected before and after the main meal. Interestingly, our results showed that Nesf-1-immunoreactive cells were distributed in Langerhans islets, co-localized with glucagon in α-cells. Similar to humans, dolphin plasma Nesf-1 concentration doesn't show a statistically significant difference when comparing fasting and post-prandial states. On the other hand, blood glucose levels were significantly higher before than after the main meal. Our data provide a comparative analysis for further studies on the involvement of Nesf-1 in mammalian metabolic disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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- View/download PDF
6. Neuronal Phenotype of col4a1 and col25a1 : An Intriguing Hypothesis in Vertebrates Brain Aging.
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Leggieri, Adele, Attanasio, Chiara, Palladino, Antonio, de Girolamo, Paolo, Lucini, Carla, and D'Angelo, Livia
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AGING , *AGE of onset , *PHENOTYPES , *VERTEBRATES , *ENDOTHELIAL cells , *EXTRACELLULAR matrix - Abstract
Collagens are the most abundant proteins in vertebrates and constitute the major components of the extracellular matrix. Collagens play an important and multifaceted role in the development and functioning of the nervous system and undergo structural remodeling and quantitative modifications during aging. Here, we investigated the age-dependent regulation of col4a1 and col25a1 in the brain of the short-lived vertebrate Nothobranchius furzeri, a powerful model organism for aging research due to its natural fast-aging process and further characterized typical hallmarks of brain aging in this species. We showed that col4a1 and col25a1 are relatively well conserved during vertebrate evolution, and their expression significantly increases in the brain of N. furzeri upon aging. Noteworthy, we report that both col4a1 and col25a1 are expressed in cells with a neuronal phenotype, unlike what has already been documented in mammalian brain, in which only col25a1 is considered a neuronal marker, whereas col4a1 seems to be expressed only in endothelial cells. Overall, our findings encourage further investigation on the role of col4a1 and col25a1 in the biology of the vertebrate brain as well as the onset of aging and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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7. Cholinergic System and NGF Receptors: Insights from the Brain of the Short-Lived Fish Nothobranchius furzeri.
- Author
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de Girolamo, Paolo, Leggieri, Adele, Palladino, Antonio, Lucini, Carla, Attanasio, Chiara, and D'Angelo, Livia
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NERVE growth factor , *MIRROR neurons , *PREOPTIC area , *FISHES , *RETICULAR formation - Abstract
Nerve growth factor (NGF) receptors are evolutionary conserved molecules, and in mammals are considered necessary for ensuring the survival of cholinergic neurons. The age-dependent regulation of NTRK1/NTRKA and p75/NGFR in mammalian brain results in a reduced response of the cholinergic neurons to neurotrophic factors and is thought to play a role in the pathogenesis of neurodegenerative diseases. Here, we study the age-dependent expression of NGF receptors (NTRK1/NTRKA and p75/NGFR) in the brain of the short-lived teleost fish Nothobranchius furzeri. We observed that NTRK1/NTRKA is more expressed than p75/NGFR in young and old animals, although both receptors do not show a significant age-dependent change. We then study the neuroanatomical organization of the cholinergic system, observing that cholinergic fibers project over the entire neuroaxis while cholinergic neurons appear restricted to few nuclei situated in the equivalent of mammalian subpallium, preoptic area and rostral reticular formation. Finally, our experiments do not confirm that NTRK1/NTRKA and p75/NGFR are expressed in cholinergic neuronal populations in the adult brain of N. furzeri. To our knowledge, this is the first study where NGF receptors have been analyzed in relation to the cholinergic system in a fish species along with their age-dependent modulation. We observed differences between mammals and fish, which make the African turquoise killifish an attractive model to further investigate the fish specific NGF receptors regulation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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8. Ontogenetic Pattern Changes of Nucleobindin-2/Nesfatin-1 in the Brain and Intestinal Bulb of the Short Lived African Turquoise Killifish.
- Author
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Montesano, Alessia, De Felice, Elena, Leggieri, Adele, Palladino, Antonio, Lucini, Carla, Scocco, Paola, de Girolamo, Paolo, Baumgart, Mario, and D'Angelo, Livia
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KILLIFISHES ,INGESTION ,ANIMAL young - Abstract
Nesfatin-1 (Nesf-1) was identified as an anorexigenic and well conserved molecule in rodents and fish. While tissue distribution of NUCB2 (Nucleobindin 2)/Nesf-1 is discretely known in vertebrates, reports on ontogenetic expression are scarce. Here, we examine the age-related central and peripheral expression of NUCB2/Nesf-1 in the teleost African turquoise killifish Nothobranchius furzeri, a consolidated model organism for aging research. We focused our analysis on brain areas responsible for the regulation of food intake and the rostral intestinal bulb, which is analogous of the mammalian stomach. We hypothesize that in our model, the stomach equivalent structure is the main source of NUCB2 mRNA, displaying higher expression levels than those observed in the brain, mainly during aging. Remarkably, its expression significantly increased in the rostral intestinal bulb compared to the brain, which is likely due to the typical anorexia of aging. When analyzing the pattern of expression, we confirmed the distribution in diencephalic areas involved in food intake regulation at all age stages. Interestingly, in the rostral bulb, NUCB2 mRNA was localized in the lining epithelium of young and old animals, while Nesf-1 immunoreactive cells were distributed in the submucosae. Taken together, our results represent a useful basis for gaining deeper knowledge regarding the mechanisms that regulate food intake during vertebrate aging. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
9. Identification and Expression of Neurotrophin-6 in the Brain of Nothobranchius furzeri: One More Piece in Neurotrophin Research.
- Author
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Leggieri, Adele, Attanasio, Chiara, Palladino, Antonio, Cellerino, Alessandro, Lucini, Carla, Paolucci, Marina, Terzibasi Tozzini, Eva, de Girolamo, Paolo, and D'Angelo, Livia
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NEUROTROPHINS , *NUCLEIC acid probes , *NERVOUS system , *MEDULLA oblongata , *OLFACTORY bulb , *IN situ hybridization - Abstract
Neurotrophins contribute to the complexity of vertebrate nervous system, being involved in cognition and memory. Abnormalities associated with neurotrophin synthesis may lead to neuropathies, neurodegenerative disorders and age-associated cognitive decline. The genome of teleost fishes contains homologs of some mammalian neurotrophins as well as a gene coding for an additional neurotrophin (NT-6). In this study, we characterized this specific neurotrophin in the short-lived fish Nothobranchius furzeri, a relatively new model for aging studies. Thus, we report herein for the first time the age-related expression of a neurotrophin in a non-mammalian vertebrate. Interestingly, we found comparable expression levels of NT-6 in the brain of both young and old animals. More in detail, we used a locked nucleic acid probe and a riboprobe to investigate the neuroanatomical distribution of NT-6 mRNA revealing a significant expression of the neurotrophin in neurons of the forebrain (olfactory bulbs, dorsal and ventral telencephalon, and several diencephalic nuclei), midbrain (optic tectum, longitudinal tori, and semicircular tori), and hindbrain (valvula and body of cerebellum, reticular formation and octavolateral area of medulla oblongata). By combining in situ hybridization and immunohistochemistry, we showed that NT-6 mRNA is synthesized in mature neurons. These results contribute to better understanding the evolutionary history of neurotrophins in vertebrates, and their role in the adult brain. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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10. Id(entifying) the inhibitor of DNA binding 3 in the brain of Nothobranchius furzeri upon aging
- Author
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Luigi Avallone, Carla Lucini, Antonio Palladino, Paolo de Girolamo, Chiara Attanasio, Livia D'Angelo, Adele Leggieri, Leggieri, Adele, Palladino, Antonio, Attanasio, Chiara, Avallone, Luigi, DE GIROLAMO, Paolo, D'Angelo, Livia, and Lucini, Carla
- Subjects
0301 basic medicine ,Aging ,Histology ,Cellular differentiation ,ved/biology.organism_classification_rank.species ,aging central nervous system fish Id3 ,Nothobranchius furzeri ,03 medical and health sciences ,0302 clinical medicine ,biology.animal ,Fundulidae ,Animals ,Killifish ,Model organism ,Molecular Biology ,Gene ,Transcription factor ,Ecology, Evolution, Behavior and Systematics ,biology ,ved/biology ,Vertebrate ,Brain ,Cell Biology ,biology.organism_classification ,Original Papers ,Cell biology ,030104 developmental biology ,Inhibitor of Differentiation Proteins ,Embryonic diapause ,Anatomy ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Inhibitors of DNA (Id) are key transcription factors (TFs) regulating neurogenic processes. They belong to the helix-loop-helix (HLH) TF family and are dominant negative regulators of basic HLH proteins (bHLHs). Specifically, they inhibit cell differentiation and enhance cell proliferation and motility. The Id family includes four members, Id1, Id2, Id3, and Id4, which have been identified in nearly all vertebrates. The transcript catalog of the African turquoise killifish, Nothobranchius furzeri, contains all four TFs and has evolved showing positive selection for Id3. N. furzeri, a teleost, is the short-lived vertebrate and is gaining increasing scientific interest as a new model organism in aging research. It is characterized by embryonic diapause, explosive sexual maturation, and rapid aging. In this study, we investigated both the expression and the role of Id3 in the brain of this model organism. Interestingly, Id3 was upregulated age-dependently along with a distribution pattern resembling that of other vertebrates. Additionally, the gene has undergone positive selection during evolution and shows a high degree of conservation relative to that of other vertebrates. These features make N. furzeri a valid tool for aging studies and a potential model in translational research.
- Published
- 2020
11. Ontogenetic Pattern Changes of Nucleobindin-2/Nesfatin-1 in the Brain and Intestinal Bulb of the Short Lived African Turquoise Killifish
- Author
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Antonio Palladino, Paola Scocco, Alessia Montesano, Paolo de Girolamo, Carla Lucini, Elena De Felice, Adele Leggieri, Livia D'Angelo, Mario Baumgart, Montesano, Alessia, De Felice, Elena, Leggieri, Adele, Palladino, Antonio, Lucini, Carla, Scocco, Paola, DE GIROLAMO, Paolo, Baumgart, Mario, and D'Angelo, Livia
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brain-gut axis ,Ontogeny ,ved/biology.organism_classification_rank.species ,lcsh:Medicine ,Article ,Nothobranchius furzeri ,03 medical and health sciences ,0302 clinical medicine ,biology.animal ,vertebrate ,medicine ,Killifish ,Model organism ,nothobranchius furzeri ,030304 developmental biology ,0303 health sciences ,Nesf-1 ,biology ,ved/biology ,business.industry ,lcsh:R ,aging ,Vertebrate ,General Medicine ,biology.organism_classification ,Epithelium ,Cell biology ,Bulb ,Nucleobindin 2 ,medicine.anatomical_structure ,brain-gut axi ,business ,030217 neurology & neurosurgery - Abstract
Nesfatin-1 (Nesf-1) was identified as an anorexigenic and well conserved molecule in rodents and fish. While tissue distribution of NUCB2 (Nucleobindin 2)/Nesf-1 is discretely known in vertebrates, reports on ontogenetic expression are scarce. Here, we examine the age-related central and peripheral expression of NUCB2/Nesf-1 in the teleost African turquoise killifish Nothobranchius furzeri, a consolidated model organism for aging research. We focused our analysis on brain areas responsible for the regulation of food intake and the rostral intestinal bulb, which is analogous of the mammalian stomach. We hypothesize that in our model, the stomach equivalent structure is the main source of NUCB2 mRNA, displaying higher expression levels than those observed in the brain, mainly during aging. Remarkably, its expression significantly increased in the rostral intestinal bulb compared to the brain, which is likely due to the typical anorexia of aging. When analyzing the pattern of expression, we confirmed the distribution in diencephalic areas involved in food intake regulation at all age stages. Interestingly, in the rostral bulb, NUCB2 mRNA was localized in the lining epithelium of young and old animals, while Nesf-1 immunoreactive cells were distributed in the submucosae. Taken together, our results represent a useful basis for gaining deeper knowledge regarding the mechanisms that regulate food intake during vertebrate aging.
- Published
- 2020
12. Translational relevance of forward genetic screens in animal models for the study of psychiatric disease.
- Author
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Sheardown, Eva, Mech, Aleksandra M., Petrazzini, Maria Elena Miletto, Leggieri, Adele, Gidziela, Agnieszka, Hosseinian, Saeedeh, Sealy, Ian M., Torres-Perez, Jose V., Busch-Nentwich, Elisabeth M., Malanchini, Margherita, and Brennan, Caroline H.
- Subjects
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GENETIC testing , *MENTAL illness , *ANIMAL models in research , *FRUIT flies , *HUMAN biology , *GENOTYPE-environment interaction - Abstract
Psychiatric disorders represent a significant burden in our societies. Despite the convincing evidence pointing at gene and gene-environment interaction contributions, the role of genetics in the etiology of psychiatric disease is still poorly understood. Forward genetic screens in animal models have helped elucidate causal links. Here we discuss the application of mutagenesis-based forward genetic approaches in common animal model species: two invertebrates, nematodes (Caenorhabditis elegans) and fruit flies (Drosophila sp.); and two vertebrates, zebrafish (Danio rerio) and mice (Mus musculus), in relation to psychiatric disease. We also discuss the use of large scale genomic studies in human populations. Despite the advances using data from human populations, animal models coupled with next-generation sequencing strategies are still needed. Although with its own limitations, zebrafish possess characteristics that make them especially well-suited to forward genetic studies exploring the etiology of psychiatric disorders. • Assays of core component behaviors associated with human psychiatric disease are established. • Behavioral screens in animal models predict loci affecting human behavior. • Next generation sequencing facilitates identification of candidate mutations. • Combining human and animal studies reveals the biology of human psychiatric disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
13. EXPRESSION OF TRKA RECEPTOR IN ADULT ZEBRAFISH BRAIN
- Author
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Adriana Petrovici, Adele Leggieri, Luciana Castaldo, Lucianna Maruccio, Carmen Solcan, Carla Lucini, VARI, Petrovici, Adriana, Leggieri, Adele, Castaldo, Luciana, Maruccio, Lucianna, Solcan, Carmen, and Lucini, Carla
- Subjects
TRKA, ZEBRAFISH, BRAIN - Abstract
In our previous study, the presence and distribution of nerve growth factor (NGF) were described in adult zebrafish brain [1]. In mammals, the signaling of mature NGF (mNGF) is transduced by the tropomyosin receptor kinase A (TrkA) and acts as mediator in many essential functions in the central nervous system. Since TrkA expression was described in developing zebrafish [2], the aim of the present study is to describe the pattern of distribution of TrkA mRNA in the brain of adult zebrafish. The investigation was conducted on brain fixed in paraformaldehyde. Sections were firstly incubated overnight with digoxigenin-labeled riboprobes for TrkA [2] and then with anti-digoxigenin Fab fragments conjugated with alkaline phosphatase. The chromogenic reaction was carried out by using Fast Red substrate. After counterstaining with DAPI, sections were visualized in fluorescence microscopy. In the telencephalon, TrkA mRNA was found in the olfactory bulbs, specifically in the glomerular layer and in the external cellular layer. In addition, some positive round small neurons were seen in the regions of the dorsal area and rare positive neurons in the ventral area. In the diencephalon, TrkA mRNA was seen in some neurons of the hypothalamus, in few neurons of mammillary body and synencephalon. In the mesencephalon, TrkA mRNA was detected in neurons of the optic tectum, specifically in the periventricular grey zone and superficial grey and white zone, and in neurons of the semicircular tori. Concerning rhombencephalon, TrkA mRNA was highly present in neurons of all regions of the cerebellum, and in neurons of cerebellar crest. Our study highlighted the wide expression of TrkA receptor throughout all brain regions of adult zebrafish. In mammals, this receptor mediates the action of mNGF [3]. However, in zebrafish brain extracts, only the immature form of NGF (pro NGF) was found. These findings suggest a different NGF signaling in zebrafish or the presence of low and fleeting undetectable quantities of mNGF. Cacialli P et al. Nerve growth factor is expressed and stored in central neurons of adult zebrafish. J Anat. Apr 4. doi: 10.1111/joa.12986, 2019. [2] Nittoli V. et al. A comprehensive analysis of neurotrophins and neurotrophin tyrosine kinase receptors expression during development of zebrafish. J Comp Neurol, 526:1057–1073, 2018. [3] Bucci C et al. The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors. Membranes 4(4), 642-677; 2014.
- Published
- 2019
14. The Case Study of Nesfatin-1 in the Pancreas of Tursiops truncatus
- Author
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C. Gatta, Paola Scocco, Carla Lucini, Ettore Varricchio, Elena De Felice, Adele Leggieri, Antonio Palladino, Marina Paolucci, L. Maruccio, Paolo de Girolamo, Livia D'Angelo, Gatta, Claudia, De Felice, Elena, D’Angelo, Livia, Maruccio, Lucianna, Leggieri, Adele, Lucini, Carla, Palladino, Antonio, Paolucci, Marina, Scocco, Paola, Varricchio, Ettore, and DE GIROLAMO, Paolo
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Physiology ,type 2 diabetes mellitus ,medicine.medical_treatment ,Central nervous system ,Glucagon ,lcsh:Physiology ,glycemic state ,03 medical and health sciences ,Physiology (medical) ,Internal medicine ,medicine ,pancreas ,Nesf-1, pancreas, common bottlenose dolphin, glycemic state, type 2 diabetes mellitus ,Meal ,Nesf-1 ,lcsh:QP1-981 ,biology ,Insulin ,Type 2 Diabetes Mellitus ,Brief Research Report ,Bottlenose dolphin ,biology.organism_classification ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Pancreas ,Homeostasis ,common bottlenose dolphin - Abstract
Nesfatin-1 (Nesf-1) is an anorexigenic peptide involved in the regulation of homeostatic feeding. Nesf-1 is expressed in the central nervous system and other organs, including pancreas, where it promotes the release of insulin from β-cells. This raises the possibility that Nesf-1 dysfunction could be involved in metabolic disorders, particularly in type 2 diabetes mellitus (T2D). Recently, it has been discovered that dolphins can be a natural animal model that fully replicates human T2D, due to its prolonged glucose tolerance curve and maintenance of a state of hyperglycemia similar to human T2D during fasting. This correspondence suggests that dolphins may be a suitable model for investigating physiological and pathological metabolic disorders. Here, we have characterized Nesf-1 distribution in the pancreas of the common bottlenose dolphin (Tursiops truncatus) and measured plasmatic levels of Nesf-1 and glucose during fasting and post-prandial states. The Mediterranean Marine Mammal Tissue Bank (MMMTB) of the University of Padova provided us with pancreas samples, derived from four animals, and plasma samples, collected before and after the main meal. Interestingly, our results showed that Nesf-1-immunoreactive cells were distributed in Langerhans islets, co-localized with glucagon in α-cells. Similar to humans, dolphin plasma Nesf-1 concentration doesn’t show a statistically significant difference when comparing fasting and post-prandial states. On the other hand, blood glucose levels were significantly higher before than after the main meal. Our data provide a comparative analysis for further studies on the involvement of Nesf-1 in mammalian metabolic disorders.
- Published
- 2018
15. Housing and Husbandry Factors Affecting Zebrafish ( Danio rerio ) Novel Tank Test Responses: A Global Multi-Laboratory Study.
- Author
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Hillman C, Fontana BD, Amstislavskaya TG, Gorbunova MA, Altenhofen S, Barthelson K, Bastos LM, Borba JV, Bonan CD, Brennan CH, Farias-Cea A, Cooper A, Corcoran J, Dondossola ER, Martinez-Duran LM, Gallas-Lopes M, Galstyan DS, Garcia EO, Gerken E, Hindges R, Kenney JW, Kleshchev MA, Kolesnikova TO, Leggieri A, Khatsko SL, Lardelli M, Lodetti G, Lombardelli G, Luchiari AC, Portela SM, Medan V, Moutinho LM, Nekhoroshev EV, Petersen BD, Petrunich-Rutherford ML, Piato A, Porfiri M, Read E, Resmim CM, Rico EP, Rosemberg DB, de Abreu MS, Salazar CA, Stahloher-Buss T, Teixeira JR, Valentim AM, Zhdanov AV, Iturriaga-Vásquez P, Wang X, Wong RY, Kalueff AV, and Parker MO
- Abstract
The reproducibility crisis in bioscience, characterized by inconsistent study results, impedes our understanding of biological processes and global collaborative studies offer a unique solution. This study is the first global collaboration using the zebrafish ( Danio rerio ) novel tank test, a behavioral assay for anxiety-like responses. We analyzed data from 20 laboratories worldwide, focusing on housing conditions and experimental setups. Our study included 488 adult zebrafish, tested for 5 min, focusing on a variety of variables. Key findings show females exhibit more anxiety-like behavior than males, underscoring sex as a critical variable. Housing conditions, including higher stocking densities and specific feed types, influenced anxiety levels. Optimal conditions (5 fish/L) and nutritionally rich feeds (e.g., rotifers), mitigated anxiety-like behaviors. Environmental stressors, like noise and transportation, significantly impacted behavior. We recommend standardizing protocols to account for sex differences, optimal stocking densities, nutritionally rich feeds, and minimizing stressors to improve zebrafish behavioral study reliability., Competing Interests: Competing Interest Statement: The authors declare no competing interests.
- Published
- 2024
- Full Text
- View/download PDF
16. rbfox1 loss of function in zebrafish leads to dysregulation in bdnf/trkb2 and pac1a expression resulting in HPI axis hyperactivation, altered stress response and allostatic overload.
- Author
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Leggieri A, García-González J, Hosseinian S, Ashdown P, Anagianni S, Wang X, Havelange W, Fernàndez-Castillo N, Cormand B, and Brennan CH
- Abstract
RBFOX1 regulates transcriptional networks linked to synaptic transmission and neurodevelopment. Mutations in the RBFOX1 gene are associated with psychiatric disorders but how RBFOX1 influences psychiatric disorder vulnerability remains unclear. Recent studies showed that RBFOX1 mediates the alternative splicing of PAC1, a critical HPA axis activator. Further, RBFOX1 dysfunction is linked to dysregulation of BDNF/TrkB, a pathway promoting neuroplasticity, neuronal survival, and stress resilience. Hence, RBFOX1 dysfunction may increase psychiatric disorder vulnerability via HPA axis dysregulation, leading to disrupted development and allostatic overload. To test this hypothesis, we generated a zebrafish rbfox1 loss of function (LoF) line and examined behavioural and molecular effects during development. In larvae and adults, rbfox1 LoF resulted in hyperactivity, impulsivity and hyperarousal, and alterations in proliferation, fertility and survival, traits associated with allostatic overload. In larvae, rbfox1 LoF disrupted expression of pac1a, bdnf, trkb2 , and HPI axis genes. These latter were restored after chronic TrkB agonist/antagonist treatment. In adults, bdnf/trkb2 and HPI axes dysregulation was only seen following acute stress. Our findings revealed a strict interplay between RBFOX1 and BDNF/TrkB in stress resilience and suggest that RBFOX1 LoF predisposes to psychiatric diseases through HPA axis hyperactivation during development, impairing adaptation and heightening vulnerability to allostatic overload., Competing Interests: CONFLICT OF INTEREST The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2024
- Full Text
- View/download PDF
17. Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in a zebrafish model.
- Author
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Antón-Galindo E, Adel M, García-Gonzalez J, Leggieri A, López-Blanch L, Irimia M, Norton WH, Brennan CH, Fernàndez-Castillo N, and Cormand B
- Abstract
RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the effect of rbfox1 deficiency on behaviour, we used rbfox1
sa15940 , a rbfox1 loss-of-function line. We found that rbfox1sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 loss-of-function line with a different genetic background, rbfox1del19 , and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1sa15940 fish. Taken together, these results suggest that rbfox1 deficiency leads to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1 -deficient mice and in patients with different psychiatric conditions. Our study thus highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest.- Published
- 2023
- Full Text
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18. Ontogenetic Pattern Changes of Nucleobindin-2/Nesfatin-1 in the Brain and Intestinal Bulb of the Short Lived African Turquoise Killifish.
- Author
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Montesano A, De Felice E, Leggieri A, Palladino A, Lucini C, Scocco P, de Girolamo P, Baumgart M, and D'Angelo L
- Abstract
Nesfatin-1 (Nesf-1) was identified as an anorexigenic and well conserved molecule in rodents and fish. While tissue distribution of NUCB2 (Nucleobindin 2)/Nesf-1 is discretely known in vertebrates, reports on ontogenetic expression are scarce. Here, we examine the age-related central and peripheral expression of NUCB2/Nesf-1 in the teleost African turquoise killifish Nothobranchius furzeri , a consolidated model organism for aging research. We focused our analysis on brain areas responsible for the regulation of food intake and the rostral intestinal bulb, which is analogous of the mammalian stomach. We hypothesize that in our model, the stomach equivalent structure is the main source of NUCB2 mRNA, displaying higher expression levels than those observed in the brain, mainly during aging. Remarkably, its expression significantly increased in the rostral intestinal bulb compared to the brain, which is likely due to the typical anorexia of aging. When analyzing the pattern of expression, we confirmed the distribution in diencephalic areas involved in food intake regulation at all age stages. Interestingly, in the rostral bulb, NUCB2 mRNA was localized in the lining epithelium of young and old animals, while Nesf-1 immunoreactive cells were distributed in the submucosae. Taken together, our results represent a useful basis for gaining deeper knowledge regarding the mechanisms that regulate food intake during vertebrate aging., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
- Full Text
- View/download PDF
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