小鼠慢性酒精中毒及戒断过程中抑郁样行为的改变及其共病机制OA北大核心CSCDCSTPCD
Change of depression-like behavior in chronic alcoholism and withdrawal model, and co-mechanism of depression and chronic alcoholism in mice
目的:研究小鼠慢性酒精中毒及戒断过程中抑郁样行为的改变,进一步探讨酒精中毒与抑郁症的共病机制。方法:构建新型慢性酒精中毒小鼠模型;实验分为正常对照组及慢性酒精7 d、14 d、21 d和28 d组。在第6、13、20和27天分别进行酒精偏好度测试,测试后戒断酒精1 d,随后次日进行抑郁行为学测试,测试结束后处死小鼠取海马与额叶皮层,采用高效液相色谱法测定5-羟色胺(5-HT)及去甲肾上腺素(NE)含量,采用免疫印迹法测定cAMP反应元件结合蛋白( CREB)和脑源性神经营养因子( BDNF)的含量。结果:随着酒精饮酒天数及戒断次数的增加,小鼠表现出明显嗜酒现象,并且在强迫游泳和悬尾测试中,表现出明显的不动时间增加。7d组小鼠额叶皮层内5-HT水平升高(P<0.05),海马与额叶5-HT水平在21 d与28 d组降低(P<0.01);7 d和14 d组小鼠海马与额叶NE水平无明显变化,21 d和28 d组NE水平降低( P<0.05)。21 d和28 d组小鼠海马与额叶内p-CREB/CREB比值及BDNF表达水平明显下降( P<0.05),7 d与14 d组无明显变化。结论:酒精中毒、戒断阶段与抑郁的共病机制涉及5-HT。5-HT-cAMP-CREB-BDNF信号转导通路可能为酒精中毒与抑郁症的共病机制。
AIM: To investigate the behavior of depression in chronic alcoholism and withdrawal model of mice, and to explore the co-mechanism of alcoholism and depression.METHODS: A novel model of chronic alcoholism was constructed in this study.The animals were divided into normal control group, and alcohol 7 d, 14 d, 21 d and 28 d groups.The mice were given alcohol preference test on the 6th, 13th, 20th and 27th days.After the test, alcohol were withdrawn for 1 d, then the next day the mice were given behavior test of depression.After the test, the mice were sacri-ficed.The contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) were detected by HPLC.The expression of cAMP response element-binding protein ( CREB) and brain-derived neurotrophic factor ( BDNF) was detected by Western blot.RESULTS:The mice showed an obvious drinking phenomenon, and the immobility time of forced swimming test and tail suspension test was significantly increased, with increasing drinking days and withdrawal times.5-HT level in 7 d group mice only increased in frontal cortex (P<0.05).However, compared with control group, 5-HT levels in hippocampus and cortex were decreased on the 21th and 28th days (P<0.01).NE levels in 21 d and 28 d groups were decreased in hippo-campus and frontal cortex (P<0.05), and no significant change was observed in 7 d and 14 d groups.The protein levels of p-CREB and BDNF were significantly decreased in hippocampus and frontal cortex of 12 d and 28 d groups (P<0.05), and no significant change was observed in 7 d group and 14 d group.CONCLUSION:The co-mechanism of alcoholism, withdrawal and depression is related to 5-HT.5-HT-cAMP-CREB-BDNF signaling pathway may be a common mechanism for alcoholism and depression.
蒋曦;田福荣;赵应征
宁波明州医院药剂科,浙江宁波315100温州医科大学,浙江温州325035温州医科大学,浙江温州325035
基础医学
酒精中毒抑郁5-羟色胺cAMP反应元件结合蛋白脑源性神经营养因子
AlcoholismDepression5-hydroxytryptaminecAMP response element-binding proteinBrain-derived neurotrophic factor
《中国病理生理杂志》 2016 (2)
296-301,6
国家自然科学基金资助项目(No.81272160)
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