Altered adult hippocampal neuronal maturation in a rat model of fetal alcohol syndrome
Altered adult hippocampal neuronal maturation in a rat model of fetal alcohol syndrome
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DOI：
10.1016/j.brainres.2011.01.116
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发表时间：
2011-04-12
期刊：
影响因子：
2.9
通讯作者：
Christie, Brian R.
中科院分区：
文献类型：
--
作者：
Gil-Mohapel, Joana;Boehme, Fanny;Christie, Brian R.
怀孕期间接触乙醇可能对发育中的神经系统造成破坏，导致严重的中枢神经系统功能障碍。海马体是神经发生持续到成年的两个大脑区域之一，对乙醇的致畸作用特别敏感。在本研究中，我们测试了胎儿酒精综合征（FAS）的大鼠模型，通过灌胃给予乙醇在整个三个月的当量。随后，我们评估了青春期（35天），年轻成年（60天）和成年（90天）Sprague-Dawley大鼠海马齿状回的细胞增殖，以及神经元存活和分化。使用外源性（溴脱氧尿苷）和内源性（Ki-67）标记物，我们观察到乙醇暴露的动物细胞增殖和生存没有显着变化时，与他们的配对喂养和随意对照。然而，我们检测到在所有三个月当量中暴露于乙醇的动物中新的未成熟神经元的数量显着增加。这一结果可能反映了一种补偿机制，以抵消产前乙醇暴露或乙醇诱导的神经原性过程在早期神经元成熟阶段的逮捕的有害影响。综上所述，这些结果表明，暴露于乙醇在大脑发育期间会导致神经原性过程的长期失调，这可能是一种机制，至少在一定程度上，已报告的FAS啮齿动物模型中的海马赤字。(C)2011 Elsevier B. V.保留所有权利。
Exposure to ethanol during pregnancy can be devastating to the developing nervous system, leading to significant central nervous system dysfunction. The hippocampus, one of the two brain regions where neurogenesis persists into adulthood, is particularly sensitive to the teratogenic effects of ethanol. In the present study, we tested a rat model of fetal alcohol syndrome (FAS) with ethanol administered via gavage throughout all three trimester equivalents. Subsequently, we assessed cell proliferation, as well as neuronal survival, and differentiation in the dentate gyrus of the hippocampus of adolescent (35 days old), young adult (60 days old) and adult (90 days old) Sprague-Dawley rats. Using both extrinsic (bromodeoxyuridine) and intrinsic (Ki-67) markers, we observed no significant alterations in cell proliferation and survival in ethanol-exposed animals when compared with their pair-fed and ad libitum controls. However, we detected a significant increase in the number of new immature neurons in animals that were exposed to ethanol throughout all three trimester equivalents. This result might reflect a compensatory mechanism to counteract the deleterious effects of prenatal ethanol exposure or an ethanol-induced arrest of the neurogenic process at the early neuronal maturation stages. Taken together these results indicate that exposure to ethanol during the period of brain development causes a long-lasting dysregulation of the neurogenic process, a mechanism that might contribute, at least in part, to the hippocampal deficits that have been reported in rodent models of FAS. (C) 2011 Elsevier B.V. All rights reserved.