title: JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.
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.
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: H
authors.identifier: 0000-0002-5309-4034
authors.initials: H
authors.lastname: Mohammad
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: F
authors.initials: F
authors.lastname: Marchisella
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Ortega-Martinez
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Hollos
authors.affiliation: University of Turku, Turku, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Eerola
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Komulainen
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Kulesskaya
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Freemantle
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Fagerholm
authors.affiliation: University of Turku, Turku, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Savontaus
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Rauvala
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Peterson
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD, USA.
authors.forename: H
authors.identifier: 0000-0002-5727-434X
authors.initials: H
authors.lastname: van Praag
authors.affiliation: Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, Turku, Finland.
authors.forename: E T
authors.initials: ET
authors.lastname: Coffey
mesh_terms: D000339:Affect; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000503:physiopathology; D001008:Anxiety Disorders / Q000209:etiology / Q000378:metabolism; D001522:Behavior, Animal; D049109:Cell Proliferation; D003863:Depression / Q000209:etiology / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology
chemical_list: D048055:Mitogen-Activated Protein Kinase 8