Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation.
Nat Neurosci
; 24(8): 1100-1109, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34183865
The rapidly acting antidepressants ketamine and scopolamine exert behavioral effects that can last from several days to more than a week in some patients. The molecular mechanisms underlying the maintenance of these antidepressant effects are unknown. Here we show that methyl-CpG-binding protein 2 (MeCP2) phosphorylation at Ser421 (pMeCP2) is essential for the sustained, but not the rapid, antidepressant effects of ketamine and scopolamine in mice. Our results reveal that pMeCP2 is downstream of BDNF, a critical factor in ketamine and scopolamine antidepressant action. In addition, we show that pMeCP2 is required for the long-term regulation of synaptic strength after ketamine or scopolamine administration. These results demonstrate that pMeCP2 and associated synaptic plasticity are essential determinants of sustained antidepressant effects.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Encéfalo
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Fator Neurotrófico Derivado do Encéfalo
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Proteína 2 de Ligação a Metil-CpG
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Antidepressivos
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Plasticidade Neuronal
Limite:
Animals
Idioma:
En
Revista:
Nat Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos