摘要
目的研究铜腙诱导的脱髓鞘小鼠是否对慢性不可预测应激诱导的抑郁样行为更加易感，以及其潜在神经病理学改变。方法C57BL／6小鼠随机分为对照组（n=10），慢性不可预测应激组（n=12），铜腙喂养组（n=12），铜腙喂养联合慢性不可预测性应激组（n=12），经过3周应激及铜腙喂养后，测量各组动物自发活动、焦虑水平以及抑郁样行为变化，并检测脑的髓鞘标志蛋白碱性磷酸蛋白（MBP）及星型胶质细胞标志物胶质纤维酸性蛋白（GFAP）的表达水平。结果慢性不可预测性应激不影响铜腙诱导脱髓鞘小鼠的自发活动、焦虑水平以及糖水偏好程度，但显著提高其在强迫游泳实验中的不动时间[对照组（109．3±8．0）s，应激组（111．3±21．8）s，铜腙组（90．5±8．9）s，铜腙＋应激组（155．0±9．1）s]，差异具有统计学意义（P〈0．05），Western blot检测显示慢性不可预测应激显著降低铜腙诱导脱髓鞘小鼠的MBP表达[对照组（1．014±0．060），应激组（1．088±0．104），铜腙组（0．436±0．071），铜腙＋应激组（0．150±0．041），P〈0．05]，提高GFAP表达水平[对照组（1．026±0．045），应激组（0．846±0．078），铜腙组（1．736±0．215），铜腙＋应激组（2．428±0．314），P〈0．05]，而应激对进食正常饲料的小鼠则无此效应。结论脱髓鞘病理损伤提高个体对慢性应激的易感性，慢性应激诱导抑郁样行为产生可能由少突胶质细胞／髓鞘损伤所介导。
Objective To investigate whether cuprizone-induced demyelinating mice is more sus- ceptible to developing depressive-like behaviors induced by chronic unpredictable stress （ CUS）, and to examine the underlying neuropathological changes. Methods C57BL/6 mice were randomly divided into four groups：control （ n= 10） ,stress （ n= 12） ,cuprizone （ n= 12） and cuprizone＋stress group （ n= 12）. Mice in stress group were exposed to CUS for 3 weeks and mice in cuprizone group were fed with 0.3% cuprizone- containing food for 3 weeks. Mice in cuprizone＋stress group were exposed to both stress and euprizone, and mice in control group were fed with normal food without exposure to stress. After 3 week exposure, they were subjected to behavioral tests including spontaneous activity, anxiety level and depressive-like behaviors and their brains were possessed for Western blot to test myelin marker MBP and astroeyte activation marker GFAP. Results CUS did not change the locomotor activity, anxiety levels and sucrose preference of euprizone-induced demylinating mice, but did significantly increase their immobile time in forced swimming test （control （ 109.3±8.0）s, stress （ 111.3±21.8）s,cuprizone （90.5±8.9） s,cuprizone＋stress （155.0±9.1）s）. Western blot revealed that CUS further decreased MBP expression （control （ 1.014±0.06）, stress （ 1.088±0.104）, cuprizone （ 0.436±0.071 ）, cuproznie＋stress （ 0.150±0.041 ）, （P〈0.05） ） and increased GFAP content （ control （ 1.026±0.045 ）, stress （ 0.846±0.078 ）, cuprizone （ 1.736±0.215 ）, cuprizone ＋ stress （ 2.428±0.314）, （P〈0.05）） in cuprizone-induced demyelinating mice. Conclusion Our findings suggest that demy-elinating pathology increases individual susceptibility to chronic stress, which may induce depressive behaviors through damage of oligodendrocyte/myelin.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2016年第10期871-876,共6页
Chinese Journal of Behavioral Medicine and Brain Science
关键词
慢性不可预测应激
铜腙
脱髓鞘
碱性磷酸蛋白
胶质纤维酸性蛋白
抑郁症
Chronic unpredictable stress
Cuprizone
Demyelination
Myelin basic protein
Glial frillary acidic protein
Major depressive disorder
