JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche
Articolo
Data di Pubblicazione:
2018
Citazione:
JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche / H. Mohammad, F. Marchisella, S. Ortega-Martinez, P. Hollos, K. Eerola, E. Komulainen, N. Kulesskaya, E. Freemantle, V. Fagerholm, E. Savontous, H. Rauvala, B. Peterson, H. van Praag, E. Coffey. - In: MOLECULAR PSYCHIATRY. - ISSN 1359-4184. - 23:2(2018), pp. 362-374. [10.1038/mp.2016.203]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
N-terminal kinase; cerebellar granule neurons; C-Jun; denrde gyrus; dorsoventral axis; glucocorticoid-receptor-mechanisms; molecular-mechanisms; ventral hippocampus; cerebral-ishemia; major depression
Elenco autori:
H. Mohammad, F. Marchisella, S. Ortega-Martinez, P. Hollos, K. Eerola, E. Komulainen, N. Kulesskaya, E. Freemantle, V. Fagerholm, E. Savontous, H. Rauvala, B. Peterson, H. van Praag, E. Coffey
Link alla scheda completa:
Link al Full Text: