Mitogen- and stress-activated kinases regulate progenitor cell proliferation and neuron development in the adult dentate gyrus.
Mitogen- and stress-activated kinases regulate progenitor cell proliferation and neuron development in the adult dentate gyrus.
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DOI：
10.1111/jnc.12035
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发表时间：
2012-12
影响因子：
4.7
通讯作者：
Obrietan K
中科院分区：
文献类型：
--
作者：
Choi YS;Karelina K;Alzate-Correa D;Hoyt KR;Impey S;Arthur JS;Obrietan K
齿状回颗粒下带(SGZ)内的神经源性壁龛是终生新神经元的来源。有趣的是，SGZ的增殖能力受生理和病理生理条件的调节。一个悬而未决的问题涉及调控基础和可诱导成人神经发生的分子机制。在这里，我们研究了MAPK调节的激酶MSK1和MSK2(丝裂原和应激激活激酶1和2)作为齿状回SGZ前体细胞增殖和神经发生的调节因子的作用。在基础条件下，MSK1/2基因缺失小鼠的祖细胞增殖能力显著降低，DCX阳性未成熟神经元的数量也随之减少。值得注意的是，在MSK1/2基因缺失的小鼠中，癫痫诱导的祖细胞增殖完全被阻断。在MSK1/2基因缺失的小鼠中，这种抑制细胞增殖的作用被Forsklin输注部分逆转，这表明祖细胞群体的可诱导增殖能力是完整的。此外，在MSK1/2基因缺失的小鼠中，DCX阳性的未成熟神经元的轴突分枝减少。综上所述，这些数据揭示了MSK1/2作为基础和活性依赖的祖细胞增殖和形态成熟的调节因子在SGZ中的关键作用。
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 MSK1 and MSK2 (mitogen and stress activated kinase 1 and 2) 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 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. Further, 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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影响因子：
5.3
作者：
Li, Yi;Peng, Zechun;Xiao, Bo;Houser, Carolyn R.
通讯作者：
Houser, Carolyn R.
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
DOI：
10.1073/pnas.182296499
发表时间：
2002-09-03
影响因子：
11.1
作者：
Jin, KL;Zhu, YH;Greenberg, DA
通讯作者：
Greenberg, DA
影响因子：
5.3
作者：
Hao, YL;Creson, T;Chen, G
通讯作者：
Chen, G
影响因子：
3.4
作者：
Hartl, Daniela;Irmler, Martin;Klose, Joachim
通讯作者：
Klose, Joachim