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Mitogen‐ and stress‐activated kinases regulate progenitor cell proliferation and neuron development in the adult dentate gyrus
Author(s) -
Choi YunSik,
Karelina Kate,
AlzateCorrea Diego,
Hoyt Kari R.,
Impey Soren,
Arthur J. Simon,
Obrietan Karl
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12035
Subject(s) - neurogenesis , subgranular zone , dentate gyrus , progenitor cell , doublecortin , biology , microbiology and biotechnology , neuroscience , progenitor , neural stem cell , stem cell , subventricular zone , hippocampus
The neurogenic niche within the subgranular zone ( SGZ ) of the dentate gyrus is a source of new neurons throughout life. Interestingly, SGZ proliferative capacity is regulated by both physiological and pathophysiological conditions. One outstanding question involves the molecular mechanisms that regulate both basal and inducible adult neurogenesis. Here, we examined the role of the MAPK ‐regulated kinases, mitogen‐ and stress‐activated kinase ( MSK )1 and MSK 2. as regulators of dentate gyrus SGZ progenitor cell proliferation and neurogenesis. Under basal conditions, MSK 1/2 null mice exhibited significantly reduced progenitor cell proliferation capacity and a corollary reduction in the number of doublecortin ( DCX )‐positive immature neurons. Strikingly, seizure‐induced progenitor proliferation was totally blocked in MSK 1/2 null mice. This blunting of cell proliferation in MSK 1/2 null mice was partially reversed by forskolin infusion, indicating that the inducible proliferative capacity of the progenitor cell population was intact. Furthermore, in MSK 1/2 null mice, DCX ‐positive immature neurons exhibited reduced neurite arborization. Together, these data reveal a critical role for MSK 1/2 as regulators of both basal and activity‐dependent progenitor cell proliferation and morphological maturation in the SGZ .