Neonatal ethanol exposure reduces AMPA but not NMDA receptor levels in the rat neocortex

Neonatal ethanol exposure reduces AMPA but not NMDA receptor levels in the rat neocortex
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DOI:
10.1016/s0165-3806(02)00363-2
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发表时间:
2002-05-30
期刊:
DEVELOPMENTAL BRAIN RESEARCH
影响因子:
--
通讯作者:
Wilce, PA
Wilce, PA
中科院分区:
其他
文献类型:
--
作者:
Bellinger, FP;Davidson, MS;Wilce, PA

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胎儿酒精综合征(FAS)是西方社会导致智力低下的主要原因。我们用放射性配基结合和蛋白质印迹分析研究了酒精暴露后新生动物体内谷氨酸受体水平的可能变化。我们使用蒸汽室给新生Wistar大鼠从出生后4-9天开始每天3小时给它注射乙醇。分离控制组与母亲分开的时间和持续时间与蒸汽治疗相同,而正常对照组则保持正常发育。每天服用酒精会导致脑重和体重降低,以及小脑畸形(脑/体重比降低)。[H-3]MK-801(马来酸地佐利平)在PND10大鼠大脑皮质中的亲和力和最大结合量在不同治疗组之间没有差异。Western印迹分析也没有发现NMDAR1、NMDAR2A或NMDAR2B受体水平的任何变化。相反,蛋白质印迹分析显示,蒸气处理组小鼠的AMPA受体亚单位GluR1与对照组相比显著减少。在西方人中也发现了类似的减少,抗体识别GluR2和4个亚基。这些结果表明,乙醇减少了发育中的新皮质中的AMPA而不是NMDA受体,这可能是通过在发育过程中阻断NMDA受体而实现的。(C)2002 Elsevier Science B.V.保留所有权利。
Fetal alcohol syndrome (FAS) is the leading cause of mental retardation in western society. We investigated possible changes in glutamate receptor levels in neonatal animals following ethanol exposure using radioligand binding and western blot analysis. We used a vapor chamber to administer ethanol to neonatal Wistar rats 3 h a day from postnatal day (PND) 4-9. A separation control group was separated from their mothers for the same time and duration as the vapor treatment, while a normal control group was left to develop normally. Daily ethanol administrations resulted in decreased brain weight and body weight, as well as microencephaly (decreased brain:body weight ratio). Neither the affinity nor maximum binding of [H-3]MK-801 (dizoclipine maleate) in the cortex of PND10 rats differed between treatment groups. Western blot analysis also failed to reveal any changes in NMDAR1, NMDAR2A, or NMDAR2B receptor levels. In contrast, the AMPA receptor subunit GluR1 was greatly reduced in vapor-treated pups compared with control pups, as revealed by western blot analysis. A similar reduction was found in westerns with an antibody recognizing the GluR2 and 4 subunits. These results indicate that ethanol reduces AMPA rather than NMDA receptors in the developing neocortex, possibly by blocking NMDA receptors during development. (C) 2002 Elsevier Science B.V. All rights reserved.