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。
Objective To explore the mechanism through which serine/arginine-rich protein-specific kinase 2(SRPK2) mediates social memory deficit in an Alzheimer's disease(AD) model. Methods Social recognition 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. Results 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 memory loss in Alzheimer's disease and may be a new target for AD treatment.
作者
刘松燕
王志昊
李翔
王舰浩
李易易
陈洪玉
秦冬冬
李芳
余杭
高锋
王嘉贝
张茜
王雅梅
卢祖能
Liu Songyan;Wang Zhihao;Li Xiang(Department of Neurology,Research Center of Neurodegeneratire Diseases,Rermin Hospital of Wuhan Universily.Wuhan 430060)
出处
《卒中与神经疾病》
2024年第2期113-118,共6页
Stroke and Nervous Diseases
基金
国家自然科学基金青年科学基金项目(82101479)
国家重点研究计划项目(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)。
