摘要
目的建立饮入方式,慢性给予皮质酮,观察皮质酮对学习记忆和突触相关蛋白的影响。方法c57BL/6J雄性小鼠随机分为正常组和皮质酮组,每组10只。皮质酮组饮用含皮质酮的0.45%羟丙基-β-环糊精溶液,5 mg/(kg·d)。正常组动物给予0.45%羟丙基-β-环糊精溶液。造模35 d后,进行社会识别实验和水迷宫实验。行为学实验结束后,动物断头取海马,应用western blot进行突触相关蛋白测定。结果社会识别实验显示,正常组和皮质酮组对刺激鼠笼的嗅闻时间均比空鼠笼长(P<0.05)。对照组对刺激鼠2的嗅闻时间比刺激鼠1长(P<0.05)。皮质酮组对刺激鼠2的嗅闻时间与对刺激鼠1的嗅闻时间差异无显著性。水迷宫实验定位航行结果显示,皮质酮组学习能力下降,寻台潜伏期延长(P<0.05)。空间探索结果显示,皮质酮组穿台次数、进入实台象限的次数和实台象限路程均明显减少(P<0.05,P<0.05,P<0.05)。Western blot结果显示,皮质酮组突触后致密物质(postsynaptic density,PSD-95)、突触素(synapsin-1,Syn-1)和磷酸化细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)表达明显下降(P<0.01,P<0.01,P<0.05)。结论通过饮入方式,慢性给予皮质酮,动物出现社会记忆和空间学习记忆障碍,可能与海马突触相关蛋白表达下降,突触功能受损有关。
Objective To investigate the effect of chronic corticosterone administration on learning and memory and expression of synapse-related proteins in mice. Methods C57 BL /6J mice were randomly divided into control and corticosterone（ CORT） groups（ 10 mice per group）. CORT was dissolved in the vehicle（ 0. 45% hydroxypropy-β-cyclodextrin,β-CD）. Corticosterone（ 5 mg / kg / day） was orally administered in drinking water for 35 days. The control mice received vehicle（ β-CD） in drinking water during the entire experiment. Social discrimination test and Morris water test were applied to evaluate the learning and memory impairment of the model mice. Results Both the mice of control and CORT groups were more interested in social（ stranger cage） than the non-social（ empty cage） experience. The control group increased the time spent with an unfamiliar mouse（ stranger 2 cage）. The mice of CORT group were not able to discriminate between an unfamiliar（ stranger 2） and the familiar mouse（ stranger 1）. In the Morris water maze test,in contrast to the first 3 days,an increase in latency to reach the hidden platform（ P〈0. 05） was observed on day 4 in the CORT group compared with the mice of control group. CORT-treated mice showed a statistically significant decrease in the frequency in the platform,frequency in the target quadrant and distance in the target quadrant（ P〈0. 05,P〈0. 05,P〈0. 05） compared with the control group. The western blot analysis showed a notably decreased expression of PSD95,Syn-1and p-erk in hippocampus in the mice of CORT group compared with the control group. Conclusions Chronic administration of corticosterone induces learning and memory impairment and decreases the expression of synapse-related proteins.
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2016年第3期253-257,共5页
Acta Laboratorium Animalis Scientia Sinica
基金
北京市自然科学基金资助项目(资助编号:7142105)
国家自然科学基金(资助编号:31301890)
关键词
皮质酮
学习记忆
突触蛋白
小鼠
Corticosterone
Learning
Memory
Synapse-related protein
Mice
