Journal
MOLECULAR PSYCHIATRY
Volume 23, Issue 2, Pages 362-374Publisher
SPRINGERNATURE
DOI: 10.1038/mp.2016.203
Keywords
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Funding
- EU FP7 [ITN 608346]
- Academy of Finland [135090, 255537]
- Sigrid Juselius Foundation
- Doctoral Network in Molecular Biosciences at Abo Akademi University
- Finnish Graduate School of Neuroscience
- National Institute on Aging, Intramural Research Program
- Academy of Finland (AKA) [255537, 135090, 135090, 255537] Funding Source: Academy of Finland (AKA)
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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.
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