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Publication : Mitogen- and stress-activated kinases regulate progenitor cell proliferation and neuron development in the adult dentate gyrus.

First Author  Choi YS Year  2012
Journal  J Neurochem Volume  123
Issue  5 Pages  676-88
PubMed ID  23020821 Mgi Jnum  J:190950
Mgi Id  MGI:5450790 Doi  10.1111/jnc.12035
Citation  Choi YS, et al. (2012) Mitogen- and stress-activated kinases regulate progenitor cell proliferation and neuron development in the adult dentate gyrus. J Neurochem 123(5):676-88
abstractText  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 MSK2. as regulators of dentate gyrus SGZ progenitor cell proliferation and neurogenesis. Under basal conditions, MSK1/2 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 MSK1/2 null mice. This blunting of cell proliferation in MSK1/2 null mice was partially reversed by forskolin infusion, indicating that the inducible proliferative capacity of the progenitor cell population was intact. Furthermore, in MSK1/2 null mice, DCX-positive immature neurons exhibited reduced neurite arborization. Together, these data reveal a critical role for MSK1/2 as regulators of both basal and activity-dependent progenitor cell proliferation and morphological maturation in the SGZ.
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