摘要
目的探讨艾司西酞普兰对APP/PS-1小鼠海马神经元突触功能及与BDNF-TrkB-CREB信号通路的关系。方法将7月龄APP/PS-1转基因小鼠随机分为模型组及艾司西酞普兰组,每组10只;另取10只同龄C57BL/6小鼠作为阴性对照组。给予10 mg/kg艾司西酞普兰灌胃治疗,连续8周,每天一次;对照组及模型组给予等体积生理盐水。Morris水迷宫检测各组小鼠学习记忆能力;尼式染色检测各组小鼠海马DG区尼氏体变化;酶联免疫吸附实验(ELISA)检测小鼠海马区乙酰胆碱酯酶(AChE)及胆碱乙酰转移酶(ChAT);Western blot检测小鼠海马区SYN、PSD95、GAP43、BDNF、TrkB、p-TrkB、CREB及p-CREB蛋白表达。结果艾司西酞普兰组改善APP/PS-1小鼠认知功能,小鼠逃避潜伏期减少,穿越平台次数增加,在目标象限停留时间延长,小鼠海马DG区神经元排列整齐且尼氏体数量增加,下调AChE,上调ChAT表达,且能增加SYN、PSD95及GAP43蛋白表达;此外,艾司西酞普兰还能显著增加小鼠海马区BDNF、p-TrkB及p-CREB蛋白表达,与模型组相比,差异有统计学意义(P<0.05)。结论艾司西酞普兰改善小鼠海马神经元突触功能,提高APP/PS-1小鼠的学习记忆能力,可能与调控BDNF-TrkBCREB信号通路相关蛋白表达有关。
Objective To investigate the relationship between escitalopram and synaptic function in hippocampal neurons of APP/PS-1 mice and its relationship with BDNF-TrkB-CREB signaling pathway. Methods Seven-month-old APP/PS-1 transgenic mice were randomly divided into model group and escitalopram group,with 10 rats in each group. Another10 C57 BL/6 mice of the same age were used as negative control group. 10 mg/kg escitalopram was administered by gavage for8 weeks,once a day;the control group and the model group were given an equal volume of normal saline. Morris water maze was used to detect the learning and memory ability of mice in each group. Niety staining was used to detect the changes of Nissl body in hippocampus DG of each group. Enzyme-linked immunosorbent assay(ELISA)was used to detect acetylcholinesterase(AChE)and choline in hippocampus of mice. Acetyltransferase(ChAT),Western blot was used to detect the expression of SYN,PSD95,GAP43,BDNF,TrkB,p-TrkB,CREB and p-CREB in hippocampus of mice. Results The escitalopram group improved the cognitive function of the app mice. The escape latency of the mice decreased,the number of crossing platforms increased,and the residence time in the target quadrant was prolonged. The neurons in the hippocampal DG region of the mice were arranged neatly and the number of Nissl bodies increased. Down-regulation of AChE,up-regulation of ChAT expression,and increased expression of SYN,PSD95 and GAP43 proteins;In addition,escitalopram significantly increased BDNF,p-TrkB and p-CREB protein expression in mouse hippocampus,compared with the model group The difference was significantly different(P < 0.05). Conclusion Escitalopram improves the synaptic function of mouse hippocampal neurons and improves the learning and memory ability of APP/PS-1 mice,which may be related to the regulation of BDNF-TrkB-CREB signaling pathway-related protein expression.
作者
金霏
梁秋实
陈克研
吴腾飞
JIN Wei;LIANG Qiu shi;CHEN Ke yan;WU Teng fei(The First Affiliated Hospital of China Medical Uni versity,Department of Pharmacy,Shenyang 110001,China)
出处
《解剖学研究》
CAS
2020年第1期19-23,共5页
Anatomy Research
基金
辽宁省自然科学基金(20180551091).
