RESUMO
Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders.
Assuntos
Ansiedade/etiologia , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Neurogênese/fisiologia , Afeto , Animais , Ansiedade/fisiopatologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/metabolismo , Comportamento Animal , Proliferação de Células , Depressão/etiologia , Depressão/fisiopatologia , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 8 Ativada por Mitógeno/genética , Neurogênese/genética , Plasticidade Neuronal/fisiologia , Neurônios/fisiologiaRESUMO
This corrects the article DOI: 10.1038/mp.2016.203.
