长期注射皮质酮致慢性应激抑郁小鼠海马星形胶质细胞和突触结构可塑性的变化  

Effects of long-term injection of corticosterone on hippocampal astrocytes and synaptic plasticity in mice

作　　者：张绘宇[1] 赵玉男[2] 王中立[2] 

机构地区：[1]广州医科大学病理教研室,广州511436 [2]南京中医药大学病理教研室,南京210023

出　　处：《中华行为医学与脑科学杂志》2016年第1期13-18,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金（81303246）;广东省中医药局科研基金（20151274）;广州医科大学科研基金（2015C04）

摘　　要：目的 探讨长期皮质酮（Corticosterone,CORT）注射对小鼠海马星形胶质细胞和突触结构可塑性的影响.方法 将40只雄性C57BL/6N小鼠随机分为正常对照组与模型组,模型组小鼠给予连续四周的CORT皮下注射,构建慢性应激抑郁障碍小鼠模型;采用强迫悬尾和糖水偏好实验验证慢性应激模型的建立,放射免疫法测定小鼠血清中CORT水平;采用蛋白免疫印迹法测定突触囊泡蛋白（Synaptophysin,SYP）和突触后致密物-95（Postsynaptie density-95,PSD-95）的蛋白表达水平;采用免疫细胞化学和定量体视学技术,三维测量胶质纤维酸性蛋白阳性星形胶质细胞体积和细胞突起长度.结果 模型组小鼠强迫悬尾不动时间[（137.95±6.22）s]较对照组[（114.05±4.12）s]明显延长（P＜0.01）,模型组糖水偏好[（62.42±6.75）％]较对照组[（86.52±5.08）％]明显降低（P＜0.01）;抑郁小鼠的血清CORT水平[（11.48±0.62） ng/ml]比对照组[（1.11±0.05） ng/ml]明显增高（P＜0.01）;模型组海马SYP表达水平和PSD-95表达水平均比对照组[（0.54±0.04）vs（0.99±0.14）,（0.57±0.07） vs（1.03±0.10）;均P＜0.叭）明显降低;模型组星形胶质细胞体积[（132.04±9.23） μm3]和细胞突起总长度[（1.39±0.05）×107 μm],低于对照组[（168.49±9.01） μm3],[（1.77±0.10）×107 μm],差异具有统计学意义（P＜0.05,P＜0.01）.并且星形胶质细胞突起总长度缩短与海马SYP和PSD-95的蛋白表达减少呈正相关（r=0.660,P＜0.01;r=0.614,P＜0.01）.结论 长期CORT注射诱导小鼠抑郁样行为,可能与CORT缩短星形胶质细胞突起长度而致突触结构可塑性有关.Objective To study the effects of long-term injection of corticosterone （CORT） on the hippocampal astrocytes and synaptic plasticity in mice.Methods Male C57BL/6N mice （n=40） were randomly divided into control group and model group.Mice in the model group were treated with subcutaneous injection of CORT for 4 weeks to generate chronic stress depression model.Chronic stress model was proved to be established by tail suspension test and sucrose preference test and serum level of CORT was determined by radioimmunoassay.Protein expression levels of hippocampal synaptophysin （SYP） and postsynaptic density-95 （PSD-95） were detected by Western blot.Somal volume and protrusion length of glial fibrillary acidic protein-positive astrocytes were assayed by immunocytochemistry and quantitative stereological techniques.Results Immobility time in model group （（137.95±6.22） s） was significantly extended in comparison with that in the control group （（114.05 ± 4.12） s） （P＜ 0.01）.Sucrose preference in the model group （62.42 ± 6.75）％ was lower than that in the control group （86.52±5.08）％ （P＜0.01）.CORT levels in model group （（11.48±0.62） ng/ml） was significantly increased compared with that in the control group （（1.11±0.05） ng/ml） （P＜0.01）.Hippocampal SYP （0.54±0.04） and PSD-95 （0.57±0.07） expression levels in model group were lower than those in the control group （0.99±0.14）,（1.03±0.10） （P＜0.01）.Somal volume in the model group （（132.04±9.23） μm3） and protrusion length （（1.39± 0.05） × 107 μm） was lower than that in the control group （（168.49±9.01）μm3）,（1.77±0.10） × 107 μm） （P＜0.05,P＜0.01）.SYP and PSD-95 expression level was found to be positively correlated with the reduction of the protrusion length（r=0.660,P＜0.01;r=0.614,P＜0.01）in astrocytes.Conclusion The results suggest that depression-like behavior-in-duced by long-term CORT treatment is possibly caused by the alte

关 键 词：皮质酮 星形胶质细胞 抑郁症 突触 

分 类 号：R749.4[医药卫生—神经病学与精神病学]