Age-related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal in male Wistar rats.

Age-related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal in male Wistar rats.
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DOI:
10.1007/s00213-016-4439-y
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发表时间:
2017-01
期刊:
影响因子:
3.4
通讯作者:
Breese, George R.
Breese, George R.
中科院分区:
医学3区
文献类型:
--
作者:
Harper, Kathryn M.;Knapp, Darin J.;Park, Meredith A.;Breese, George R.

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对慢性酒精戒断的行为和神经免疫脆弱性随年龄而变化。在青少年和成年大鼠中研究了慢性间歇酒精(CIA)戒断后应激后焦虑样行为与杏仁核CCL2反应的关系。将青少年和成年Wistar大鼠暴露于CIA(3次5天的膳食酒精,间隔2天停药),其浓度在不同年龄的血液中产生相似的酒精水平。在最终戒断24小时后,一半的大鼠暴露于1小时的约束应激。应激后4小时,对大鼠进行行为或组织分析。与对照组相比,青少年的CIA和成人的CIA +压力增加了焦虑样行为。与对照组相比,青少年的CIA和成人的CIA和CIA +应激使CCL2 mRNA升高。与对照组相比,青少年CIA和成人CIA +应激降低了CCL2与神经元标记物NeuN的共定位。与对照组相比,CIA和CIA +应激在青少年中降低了CCL2与星形细胞标记物GFAP的共定位,但实验组与对照组在成人中没有差异。与对照组相比,青少年单独应激和成人CIA +应激降低了CCL2与小胶质标记物Iba1的共定位。CCL2蛋白的改变可能控制两种年龄的行为,但在青少年中与CIA单独有关,在成人中与CIA +应激有关。CIA和应激后表达CCL2的CeA神经元数量发生改变,与CCL2参与神经功能一致。
Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats. Adolescent and adult Wistar rats were exposed to CIA (three 5-day blocks of dietary alcohol separated by 2 days of withdrawal) at concentrations that created similar blood alcohol levels across age. Twenty-four hours into the final withdrawal, half of the rats were exposed to 1 h of restraint stress. Four hours post-stress, rats were used for behavior or tissue assays. Anxiety-like behavior was increased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 mRNA was increased versus controls by CIA in adolescents and by CIA and CIA + stress in adults. CCL2 co-localization with neuronal marker NeuN was decreased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 co-localization with astrocytic marker GFAP was decreased versus controls by CIA and CIA + stress in adolescents, but experimental groups did not differ from controls in adults. CCL2 co-localization with microglial marker Iba1 was decreased versus controls by stress alone in adolescents and by CIA + stress in adults. Changes in CCL2 protein might control behavior at either age but are particularly associated with CIA alone in adolescents and with CIA + stress in adults. That the number of CeA neurons expressing CCL2 was altered after CIA and stress is consistent with CCL2 involvement in neural function.
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