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http://hdl.handle.net/1843/56693| Tipo: | Artigo de Periódico |
| Título: | Contribution of neuronal calcium sensor 1 (Ncs-1) to anxiolytic-like and social behavior mediated by valproate and Gsk3 inhibition |
| Autor(es): | Luiz Alexandre Viana Magno Helia Tenza Ferrer Mélcar Collodetti Eduardo de Souza Nicolau Jivan Khlghatyan Thomas Del’Guidice Marco Aurelio Romano Silva Jean Martin Beaulieu |
| Resumo: | Peripheral biomarker and post-mortem brains studies have shown alterations of neuronal calcium sensor 1 (Ncs-1) expression in people with bipolar disorder or schizophrenia. However, its engagement by psychiatric medications and potential contribution to behavioral regulation remains elusive. We investigated the effect on Ncs-1 expression of valproic acid (VPA), a mood stabilizer used for the management of bipolar disorder. Treatment with VPA induced Ncs-1 gene expression in cell line while chronic administration of this drug to mice increased both Ncs-1 protein and mRNA levels in the mouse frontal cortex. Inhibition of histone deacetylases (HDACs), a known biochemical effect of VPA, did not alter the expression of Ncs-1. In contrast, pharmacological inhibition or genetic downregulation of glycogen synthase kinase 3β (Gsk3β) increased Ncs-1 expression, whereas overexpression of a constitutively active Gsk3β had the opposite effect. Moreover, adeno-associated virus-mediated Ncs-1 overexpression in mouse frontal cortex caused responses similar to those elicited by VPA or lithium in tests evaluating social and mood-related behaviors. These findings indicate that VPA increases frontal cortex Ncs-1 gene expression as a result of Gsk3 inhibition. Furthermore, behavioral changes induced by Ncs-1 overexpression support a contribution of this mechanism in the regulation of behavior by VPA and potentially other psychoactive medications inhibiting Gsk3 activity. |
| Assunto: | Transtorno bipolar Esquizofrenia paranoide Inibição |
| Idioma: | por |
| País: | Brasil |
| Editor: | Universidade Federal de Minas Gerais |
| Sigla da Instituição: | UFMG |
| Departamento: | MED - DEPARTAMENTO DE SAÚDE MENTAL |
| Tipo de Acesso: | Acesso Aberto |
| Identificador DOI: | https://doi.org/10.1038/s41598-020-61248-z |
| URI: | http://hdl.handle.net/1843/56693 |
| Data do documento: | 2020 |
| metadata.dc.url.externa: | https://www.nature.com/articles/s41598-020-61248-z |
| metadata.dc.relation.ispartof: | Scientifc Reports |
| Aparece nas coleções: | Artigo de Periódico |
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| Contribution of neuronal calcium sensor 1 (Ncs-1) to anxiolytic-like and social behavior mediated by valproate and Gsk3 inhibition.pdf | 1.12 MB | Adobe PDF | Visualizar/Abrir |
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