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

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Pysyväisosoite

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

Lähdeviite

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

Julkaisun nimi: JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche
Tekijä: 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.
Tekijän organisaatio: Neuroscience Center
University of Helsinki
Päiväys: 2018-02
Kieli: eng
Sivumäärä: 13
Kuuluu julkaisusarjaan: Molecular Psychiatry
ISSN: 1359-4184
DOI-tunniste: https://doi.org/10.1038/mp.2016.203
URI: http://hdl.handle.net/10138/233496
Tiivistelmä: 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.
Avainsanat: 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
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by_nc_nd
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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