神经损伤与功能重建2024，Vol.19Issue(1)：1-7,7.DOI:10.16780/j.cnki.sjssgncj.20230309
PDGFR-β/TGF-β/Smad2/3信号通路调控阿尔茨海默病血脑屏障完整性和学习记忆能力的分子机制研究
Regulatory Mechanism of Blood-brain Barrier Integrity and Learning and Memory Ability in Alzheimer's Disease via PDGFR-β/TGF-β/Smad2/3 Signal Pathway
摘要
Abstract
Objective:To investigate the molecular regulatory mechanism of integrity of blood-brain barrier(BBB)and learning and memory ability in Alzheimer's disease(AD)via PDGFR-β/TGF-β/Smad2/3 signaling pathway.Methods:Using the APP/PS1 transgenic mouse model of AD,the learning and memory abilities of mice were analyzed through water maze test and food search test.The proliferation rate and pericyte coverage rate in hippocampus were measured.The level of TGF-β R1 and its downstream signal pathway molecules,and the levels of tight junctions(TJs)were analyzed.After intraventricular microinjection with exogenous PDGF-BB and/or intraperitoneal injection with SB431542,the transgenic mice were analyzed by the above methods.After PDGF-BB and/or SB431542 treatment,permeability and transcellular resistance were tested in the BBB model in vitro.Results:Compared with the control group,APP/PS1 mice showed the learning and memory disability in the water maze test and food search test,the less proportion of desmin/lectin positive cells in the hippocampus,the lower levels of TGF-β R1,p-Smad2 and p-Smad3 protein,and the lower levels of TJs.Furthermore,exogenous PDGF-BB could significantly enhance the learning and memory ability,increase the pericyte coverage rate,raise the expression levels of TGF-β R1,p-Smad2 and p-Smad3 protein,and heighten the expression levels of TJs proteins.In contrast,SB431542 could partially inhibit the above effects of PDGF-BB treatment.In vitro tests showed that exogenous PDGF-BB could significantly reduce the final permeability coefficient of AD model group and increase the relative TEER value at 24 h;SB431542 can partially inhibit the above effects.Conclusion:PDGFR-β/TGF-β/Smad2/3 signal pathway may play a vital role in regulating the integrity of blood-brain barrier and the recovery of learning and memory ability in AD.关键词
阿尔茨海默病/血小板源性生长因子受体β/转化生长因子-β/血脑屏障完整性/学习记忆能力Key words
Alzheimer's disease/platelet-derived growth factor receptor-beta/transforming growth factor beta/blood-brain barrier integrity/learning and memory ability分类
医药卫生引用本文复制引用
申杰,姚雪榕,刘越存,徐桂华..PDGFR-β/TGF-β/Smad2/3信号通路调控阿尔茨海默病血脑屏障完整性和学习记忆能力的分子机制研究[J].神经损伤与功能重建,2024,19(1):1-7,7.基金项目
国家自然科学基金(血小板源性生长因子受体-β在脑缺血后血脑屏障修复中的作用机制研究,No.81360186 （）
PDGFR-β/TGFβ/Smad2/3信号通路在调控血脑屏障完整性的分子机制研究,No.81860228) （）
东莞市社会发展科技项目(PDGFR-β/TGFβ/Smad2/3信号通路在调控阿尔茨海默病血脑屏障完整性和神经元保护的分子机制研究,No.20211800904462 （）
基于格林模式的健康教育在缺血性脑卒中患者二级预防的应用,No.20211800900262 （）
二甲双胍对帕金森合并糖尿病患者认知功能的影响及其机制,No.20211800900492)、东莞市滨海湾中心医院高水平科研孵化基金项目(脑缺血-再灌注后星形胶质细胞在调控血脑屏障功能恢复和神经保护的分子机制研究,No.2022001) （脑缺血-再灌注后星形胶质细胞在调控血脑屏障功能恢复和神经保护的分子机制研究,No.2022001）
