Neonatal ethanol produces cerebellar deep nuclear cell loss and correlated disruption of eyeblink conditioning in adult rats
Neonatal ethanol produces cerebellar deep nuclear cell loss and correlated disruption of eyeblink conditioning in adult rats
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DOI：
10.1016/s0006-8993(02)03561-8
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发表时间：
2002-11-29
期刊：
影响因子：
2.9
通讯作者：
Goodlett, CR
中科院分区：
文献类型：
--
作者：
Green, JT;Tran, T;Goodlett, CR
在与人类妊娠晚期相当的大脑发育期间，大鼠暴饮式新生儿酒精暴露(Etoh)会导致小脑浦肯野细胞显著的、剂量依赖性的丢失，并导致眨眼经典条件反射障碍。目前还没有发表关于小脑深核神经元丢失是否也是暴饮式乙醇暴露的新生儿的结果，以及任何细胞丢失可能造成的功能后果的报道。由于眨眼适应需要小脑深层核细胞才能正常学习，我们研究了暴饮式新生儿乙醇暴露对成年大鼠深核细胞总数和眨眼适应的影响。乙醇组(n=11)出生后第4~9天给予乙醇5.25g/kg/d，平均峰值血乙醇浓度为363 mg/dl。假插管组(n=11)在出生后第4~9天接受急性胃插管，但不输注任何乙醇。非插管对照组(n=10)不插管。当大鼠至少3个月大时，他们接受成对的眨眼条件训练或不成对的训练。训练结束后，使用光学分割仪(一种无偏的体视学计数程序)获得对小脑深部核细胞总数的估计。与假插管和未插管对照组相比，乙醇组大鼠的深核细胞数量减少了约50%，这两组没有差异。在接受双眼条件反射的21只大鼠中，深核细胞的数量与眨眼条件下的学习速度之间存在高度显著的相关性(+0.80)。(C)2002 Elsevier Science B.V.保留所有权利。
Binge-like neonatal exposure to ethanol (EtOH) in rats, during the period of brain development comparable to that of the human third trimester, produces significant, dose-dependent Purkinje cell loss in the cerebellum and deficits in eyeblink classical conditioning. There are currently no published reports of whether neuronal loss in the cerebellar deep nuclei also results from binge-like neonatal exposure to EtOH and what the functional consequences of any cell loss might be. Since eyeblink conditioning requires cerebellar deep nuclear cells for normal learning to occur, we examined the effects of binge-like neonatal EtOH exposure on the total number of deep nuclear cells and eyeblink conditioning in adult rats. Group Ethanol (n=11) received EtOH doses of 5.25 g/kg/day on postnatal days 4-9, producing average peak blood alcohol concentrations of 363 mg/dl. Group Sham Intubated (n=11) underwent acute intragastric intubation on postnatal days 4-9 but did not receive any EtOH infusions. Group Unintubated Control (n = 10) did not receive any intubations. When rats were at least 3 months old, they received either paired eyeblink conditioning or unpaired training. Following training, estimates of the total number of cerebellar deep nuclear cells were obtained using the optical fractionator, an unbiased stereological counting procedure. Rats in Group Ethanol had approximately 50% fewer deep nuclear cells compared to rats in Groups Sham Intubated and Unintubated Control, which did not differ. For 21 rats that received paired eyeblink conditioning, a highly significant correlation (+0.80) was found between the number of deep nuclear cells and learning rate in eyeblink conditioning. (C) 2002 Elsevier Science B.V. All rights reserved.