JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche

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http://hdl.handle.net/10138/233496

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Mohammad , H , Marchisella , F , Ortega-Martinez , S , Hollos , P , Eerola , K , Komulainen , E , Kulesskaya , N , Freemantle , E , Fagerholm , V , Savontous , E , Rauvala , H , Peterson , B D , van Praag , H & Coffey , E T 2018 , ' JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche ' , Molecular Psychiatry , vol. 23 , no. 2 , pp. 362-374 . https://doi.org/10.1038/mp.2016.203

Title: JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche
Author: Mohammad, H.; Marchisella, F.; Ortega-Martinez, S.; Hollos, P.; Eerola, K.; Komulainen, E.; Kulesskaya, N.; Freemantle, E.; Fagerholm, V.; Savontous, E.; Rauvala, H.; Peterson, B. D.; van Praag, H.; Coffey, E. T.
Contributor organization: Neuroscience Center
University of Helsinki
Date: 2018-02
Language: eng
Number of pages: 13
Belongs to series: Molecular Psychiatry
ISSN: 1359-4184
DOI: https://doi.org/10.1038/mp.2016.203
URI: http://hdl.handle.net/10138/233496
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.
Subject: N-TERMINAL KINASE
CEREBELLAR GRANULE NEURONS
C-JUN
DENTATE GYRUS
DORSOVENTRAL AXIS
GLUCOCORTICOID-RECEPTOR
MOLECULAR-MECHANISMS
VENTRAL HIPPOCAMPUS
CEREBRAL-ISCHEMIA
MAJOR DEPRESSION
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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