Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice.
Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice.
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青少年暴饮暴食改变了小鼠的成人脑神经递质的表达，行为，大脑区域体积和神经化学。
DOI：
10.1111/j.1530-0277.2010.01385.x
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Crews FT
中科院分区：
文献类型：
--
作者：
Coleman LG Jr;He J;Lee J;Styner M;Crews FT
酗酒在人类青少年中很常见。青少年的大脑结构正在成熟，对酒精的神经毒性具有独特的敏感性。因此，青少年酗酒可能会对成年人的大脑产生长期影响，改变与酒精使用障碍相关的大脑结构和行为。为了确定青少年酗酒是否会改变成年小鼠的大脑，在青春期(出生后28-37天，每天5g/kg)给雄性C57BL/6小鼠灌胃水或酒精，并在成年期(P60-P88)进行评估。一系列神经递质特异性基因、行为测试(即反向学习、脉冲前抑制和开阔视野)，以及使用MRI和免疫组织化学的死后脑结构，被用来评估成人大脑的持续性变化。在P38，在青少年酗酒后24小时，许多神经递质基因，特别是胆碱能和多巴胺能，被乙醇处理后降低。有趣的是，多巴胺受体4型mRNA减少，并通过免疫组织化学证实。正常对照成熟(P38-P88)导致神经递质mRNA下降，平均下降56%。在青春期酒精治疗后，成年人表现出比对照组更大的基因表达下降，平均为73%。在Morris水迷宫中评估的成人空间学习不会因青少年酒精治疗而改变，但反向学习实验显示存在缺陷。MRI对成人大脑区域体积的评估表明，青少年饮酒后，成年人的嗅球和基底前脑较小。免疫组织化学分析发现基底前脑面积缩小，基底前脑胆碱能神经元减少。青少年狂欢酒精治疗降低了成人神经递质基因的表达，特别是胆碱能基因，减少了基底前脑和嗅球的体积，并导致基底前脑乙酰胆碱神经元密度降低。胆碱能神经元和前脑结构的丧失可能是青少年酗酒后成人逆转学习缺陷的基础。
Binge-drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol use disorders. In order to determine if adolescent ethanol binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5g/kg/day i.g., post-natal days P28-37) and assessed during adulthood (P60-P88). An array of neurotransmitter-specific genes, behavioral tests (i.e. reversal learning, prepulse inhibition, and open field), and post-mortem brain structure using MRI and immunohistochemistry, were employed to assess persistent alterations in adult brain. At P38, 24 hours after adolescent ethanol (AE) binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38-P88) resulted in decreased neurotransmitter mRNA, e.g. an average decrease of 56%. Following adolescent ethanol treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by adolescent ethanol treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following adolescent ethanol. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons. Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal forebrain acetylcholine neurons. Loss of cholinergic neurons and forebrain structure could underlie adult reversal learning deficits following adolescent binge drinking.
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影响因子：
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作者：
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