SRPK2介导阿尔兹海默病小鼠社交障碍的机制研究
SRPK2 mediates social memory dysfunction in a mouse model of Alzheimer's disease
刘松燕 1王志昊 1李翔 1王舰浩 1李易易 1陈洪玉 1秦冬冬 1李芳 1余杭 1高锋 1王嘉贝 1张茜 1王雅梅 1卢祖能1
作者信息
- 1. 430060 武汉大学人民医院神经内科、神经退行性疾病研究中心
- 折叠
摘要
目的 探讨丝氨酸精氨酸蛋白激酶2(Serine/arginine-rich protein-specific kinase 2,SRPK2)在阿尔兹海默病(Alzheimer's disease,AD)模型小鼠中介导社交记忆缺陷的机制.方法 通过动物行为学检测三转AD(3xTg-AD)模型小鼠的社交识别记忆(Social recognition memory,SRM),以相同月龄野生型小鼠作为对照,根据行为学表现将3xTg-AD模型小鼠分为SRM正常组及受损组,检测不同脑区SRPK2及小清蛋白(Parvalbumin,PV)的mRNA及蛋白表达水平;通过病毒注射下调3xTg-AD模型小鼠中SRPK2的表达,之后检测其对SRM和PV的mRNA及蛋白表达水平的影响.结果 3xTg-AD模型小鼠存在SRM障碍,这可能是由于SRPK2异常激活及PV下调导致的;通过抑制SRPK2的表达可以增加PV表达及改善3xTg-AD模型小鼠的SRM损伤.结论 SRPK2-PV通路参与介导阿尔兹海默病的社交识别记忆障碍,或成为AD治疗的新靶点.
Abstract
Objective To explore the mechanism through which serine/arginine-rich protein-specific ki-nase 2(SRPK2)mediates social memory deficit in an Alzheimer's disease(AD)model.Methods Social recog-nition memory(SRM)was assessed in 3xTg-AD model mice by assessing animal behavior.Wild-type mice of the same month of age were used as controls,and 3xTg-AD model mice were divided into a normal SRM group and an impaired SRM group.The mRNA and protein expression levels of SRPK2 and parvalbumin(PV)were detected.The expression of SRPK2 in 3xTg-AD model mice was downregulated through virus injection,after which the effects of SRPK2 on SRM and the mRNA and protein expression levels of PV were examined.Re-sults 3xTg-AD mice exhibited SRM impairment,which may be caused by abnormal SRPK2 activation and downregulation of the PV.Inhibition of SRPK2 expression can increase PV expression and rescue impaired SRM in 3xTg-AD mice.Conclusion The SRPK2-PV pathway is involved in mediating social recognition mem-ory loss in Alzheimer's disease and may be a new target for AD treatment.
关键词
丝氨酸精氨酸蛋白激酶2/小清蛋白/阿尔兹海默病/社交记忆Key words
SRPK2/PV/AD/Social recognition memory引用本文复制引用
基金项目
国家自然科学基金青年科学基金(82101479)
国家重点研究项目(2021YFA1302400)
湖北省实验动物研究领域项目(2022DFE021)
武汉大学人民医院交叉创新人才项目(JCRCZN-2022-002)
出版年
2024
NETL
NSTL
万方数据