Neurogenesis in adolescent brain is potently inhibited by ethanol

Neurogenesis in adolescent brain is potently inhibited by ethanol
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DOI:
10.1016/j.neuroscience.2005.08.090
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发表时间:
2006-01-01
期刊:
影响因子:
3.3
通讯作者:
Nixon, K
Nixon, K
中科院分区:
医学3区
文献类型:
--
作者:
Crews, FT;Mdzinarishvili, A;Nixon, K

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青春期是大脑逐渐变化的时期,可能有助于行为的成熟。人类青少年消耗大量的乙醇。为了研究乙醇对青春期神经祖细胞的影响,雄性大鼠(35-40日龄)用急性剂量的乙醇(1.0,2.5或5.0 g/kg,i.g.)或分别导致33、72和131 mg/dl的峰值血液水平的载体。溴脱氧尿苷(300 mg/kg i. p.)给药以标记分裂中的细胞,并在5小时处死大鼠以评估增殖,或在28天处死大鼠以评估细胞存活和分化。5小时后,溴脱氧尿苷免疫反应性分别减少了63,97和99%,在吻侧迁移流和34,71和99%,在脑室下区由1.0,2.5和5.0克/公斤的乙醇。在齿状回,乙醇减少溴脱氧尿苷免疫反应性分别为29%,40%和78%,在三个剂量。doublecortin免疫反应性的密度下降3天后,溴脱氧尿苷+细胞的数量仍然减少,在28天时,大多数海马溴脱氧尿苷+细胞共表达神经元核,神经元标记物。这些研究表明,青少年的大脑是非常敏感的急性乙醇抑制神经发生。(c)2005由Elsevier Ltd代表IBRO出版。
Adolescence is a period of progressive changes in brain that likely contribute to the maturation of behavior. Human adolescents consume large amounts of ethanol. To investigate the effects of ethanol on adolescent neural progenitor cells, male rats (35-40 days old) were treated with an acute dose of ethanol (1.0, 2.5 or 5.0 g/kg, i.g.) or vehicle that resulted in peak blood levels of 33, 72, and 131 mg/dl, respectively. Bromodeoxyuridine (300 mg/kg i.p.) was administered to label dividing cells and rats were killed at 5 h to assess pioliferation or at 28 days to assess cell survival and differentiation. After 5 h, bromodeoxyuridine-immunoreactivity was reduced by 63, 97 and 99% in the rostral migratory stream and 34, 71 and 99% in the subventricular zone by 1.0, 2.5 and 5.0 g/kg of ethanol respectively. In the dentate gyrus, ethanol reduced bromodeoxyuridine-immunoreactivity by 29, 40, and 78% at the three doses respectively. The density of doublecortin immunoreactivity was decreased after 3 days and the number of bromodeoxyuridine+ cells remained decreased at 28 days when most hippocampal bromodeoxyuridine+ cells coexpressed neuronal nuclei, a neuronal marker. These studies indicate that the adolescent brain is very sensitive to acute ethanol inhibition of neurogenesis. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.