A ausência da desiodase tipo 2 em astrócitos resulta no comportamento ansioso e depressivo em camundongos

Detalhes bibliográficos
Ano de defesa: 2017
Autor(a) principal: Bocco, Barbara Miranda Leite da Costa [UNIFESP]
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5075344
https://repositorio.unifesp.br/handle/11600/50786
Resumo: Thyroid hormone is essential for the functioning central of the nervous system. It is well known that hypothyroidism can lead to neuropsychiatric disorders, such as impairments in cognition and mood disorders. About 20% of T3 normally reaches the brain directly from the circulation and 80% is produced locally by type 2 deiodinase (D2) in astrocytes. Here we report that mice with astrocyte-specific Dio2 inactivation (Astro-D2KO) exhibit anxiety-depressive-like behavior as assessed via behavioral tests, such as elevated plus maze, tail-suspension and the forced-swimming tests, despite normal T3 serum levels observed in these animals. Remarkably, daily treadmill exercise sessions during 4-weeks corrected D2 inactivation-induced abnormalities. While no difference was observed in hippocampal neurogenesis, there was a moderate decrease in T3 signaling as shown by decreased expression of 4 genes out of 6 positively regulated by T3: Mbp (~43%), Mag (~34%), Hr (~49%) and Aldh1a1 (~61%) and increased expression in 3 genes out of 12 negatively regulated T3: Dgkg (~17%), Syce2 (~26%) and Col6a1 (~300%). Likewise, Astro-D2KO animals showed decreased mRNA levels of depressionrelated genes: Bdnf (~18%), Ntf3 (~43%), Nmdar (~26%) and GR (~20%), which were also normalized by exercise sessions. Our findings show that T3 generated by D2 in astrocytes is important for a normal T3 brain signaling and, impairments on this pathway appear to be related with pathological depression. In addition, chronic physical exercise corrected all the changes induced by D2 inactivation, confirming its role as potent antidepressive therapy.