Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics.
Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics.
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DOI：
10.1002/cne.22647
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发表时间：
2011-09-01
影响因子：
2.5
通讯作者：
Nixon, Kimberly
中科院分区：
文献类型：
--
作者：
McClain, Justin A.;Hayes, Dayna M.;Morris, Stephanie A.;Nixon, Kimberly
青春期大鼠的酗酒暴露通过改变神经祖细胞（NPC）的增殖和存活来有效地抑制成年海马神经发生;然而，尚不清楚酒精是否会导致净增殖的增加或减少。因此，在酒精使用障碍的青春期大鼠模型中评估了酒精对海马NPC细胞周期时相分布和动力学的影响。使用标记物（Ki-67、溴脱氧尿苷掺入和磷酸化组蛋白H3）的组合测量细胞周期分布，以确定细胞周期的G1、S和G2/M期内的NPC的比例。使用累积溴脱氧尿苷注射方案计算细胞周期动力学，以确定酒精对细胞周期长度和S期持续时间的影响。酗酒暴露降低了S期NPC的比例，但对G1或G2/M期没有影响，表明酒精特异性靶向细胞周期的S期。细胞周期动力学研究显示，酒精使NPC细胞周期持续时间缩短了36%，S期缩短了62%，这表明酗酒暴露加速了细胞周期的进展。预期这种效应会增加NPC增殖，这得到了酗酒暴露后海马颗粒下区Sox-2+ NPC数量轻微但显著增加的支持。这些研究表明了酒精抑制神经发生的机制，但也揭示了在酗酒暴露后一周观察到的代偿性神经发生反应的最早证据。
Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki-67, bromo-deoxy-uridine incorporation, and phospho-histone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromo-deoxy-uridine injection protocol to determine the effect of alcohol on cell cycle length and S-phase duration. Binge alcohol exposure reduced the proportion of NPCs in S-phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S-phase of the cell cycle. Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S-phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle. This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox-2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure. These studies suggest the mechanism of alcohol inhibition of neurogenesis but also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure.
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影响因子：
4.1
作者：
Gould, TJ
通讯作者：
Gould, TJ
影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
影响因子：
25
作者：
Imayoshi, Itaru;Sakamoto, Masayuki;Kageyama, Ryoichiro
通讯作者：
Kageyama, Ryoichiro
DOI：
10.1073/pnas.120552597
发表时间：
2000-06-20
影响因子：
11.1
作者：
Eisch, AJ;Barrot, M;Nestler, EJ
通讯作者：
Nestler, EJ
影响因子：
5
作者：
Catlow, Briony J.;Badanich, Kimberly A.;Sanchez-Ramos, Juan
通讯作者：
Sanchez-Ramos, Juan