Periadolescent ethanol exposure reduces adult forebrain ChAT+IR neurons: correlation with behavioral pathology.

Periadolescent ethanol exposure reduces adult forebrain ChAT+IR neurons: correlation with behavioral pathology.
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青春期乙醇暴露会减少成人前脑 ChAT+IR 神经元:与行为病理学的相关性。

DOI:
10.1016/j.neuroscience.2011.10.011
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发表时间:
2011-12-29
期刊:
影响因子:
3.3
通讯作者:
Crews, F. T.
Crews, F. T.
中科院分区:
医学3区
文献类型:
--
作者:
Ehlers, C. L.;Criado, J. R.;Wills, D. N.;Liu, W.;Crews, F. T.

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物质滥用通常始于青春期;因此,酒精在大脑发育的这一关键时期的影响尤为重要。流行病学数据表明,过量饮酒在青少年中很普遍,可能会产生持久的神经行为后果。胎儿酒精暴露后和患有WerNicke-Korsakoff综合征的成年人已证实前脑胆碱能输入丢失。在本研究中,胆碱乙酰转移酶(ChAT)免疫组织化学方法被用来评估前脑胆碱能神经元(Ch1-4),以及青春期酒精暴露后的行为变化。从PD 22-PD 57(平均血液酒精浓度为163 mg%)开始,Wistar大鼠暴露于间歇性乙醇蒸气(14小时开/10小时/天)35天。成年后,大鼠从蒸气中退出,并在强迫游泳测试中评估运动活动、惊吓反应、开阔场地的冲突行为和不动。于第71/72天处死大鼠,灌胃进行组织化学分析。酒精蒸气暴露大鼠表现为:在酒精蒸气暴露的第10天和第20天,停止24小时的蒸气输送8小时后,大鼠的运动活动增加,在戒断24小时和戒断后2周,在惊厥范式中,它们对脉冲前刺激的反应幅度显著降低,在旷场冲突中,焦虑样行为和/或更多的“去抑制”行为减少,在强迫游泳测试中更多地不动。ChAT免疫反应的定量分析显示,酒精蒸气暴露大鼠基底前脑Ch1-2和Ch3-4区的细胞计数显著减少。这种细胞数量的减少与开放领域冲突测试中较少的焦虑样和/或更多的“去抑制”行为显著相关。这些研究表明,Wistar大鼠的觉醒、情感状态、去抑制行为和ChAT+IR等行为指标都受到青春期酒精暴露和戒断的显著影响。
Substance abuse typically begins in adolescence; therefore, the impact of alcohol during this critical time in brain development is of particular importance. Epidemiological data indicate that excessive alcohol consumption is prevalent among adolescents and may have lasting neurobehavioral consequences. Loss of cholinergic input to the forebrain has been demonstrated following fetal alcohol exposure and in adults with Wernicke-Korsakoff syndrome. In the present study, immunohistochemistry for choline acetyltransferase (ChAT) was determined to assess forebrain cholinergic neurons (Ch1–4), and behavioral changes following periadolescent alcohol exposure. Wistar rats were exposed to intermittent ethanol vapor (14 hrs on/10 hrs off/day) for 35 days from PD 22-PD 57 (average blood alcohol concentration (BAC): 163 mg%). Rats were withdrawn from vapor and assessed for locomotor activity, startle response, conflict behavior in the open field, and immobility in the forced swim test, as adults. Rats were then sacrificed at day 71/72 and perfused for histochemical analyses. Ethanol vapor exposed rats displayed: increased locomotor activity 8 hrs after the termination of vapor delivery for that 24 hr period at day 10 and day 20 of alcohol vapor exposure, significant reductions in the amplitude of their responses to prepulse stimuli during the startle paradigm at 24 hrs withdrawal, and at two weeks following withdrawal, less anxiety-like and/or more “disinhibitory” behavior in the open field conflict, and more immobility in the forced swim test. Quantitative analyses of ChAT immunoreactivity revealed a significant reduction in cell counts in the Ch1–2 and Ch3–4 regions of the basal forebrain in ethanol vapor exposed rats. This reduction in cell counts was significantly correlated with less anxiety-like and/or more “disinhibitory” behavior in the open field conflict test. These studies demonstrate that behavioral measures of arousal, affective state, disinhibitory behavior and ChAT+IR, are all significantly impacted by periadolescent ethanol exposure and withdrawal in Wistar rats.
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。
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