树突棘及突触发育障碍诱发自闭症小鼠核心症状的机制

目的 探讨前额叶皮层(PFC)树突棘及突触发育障碍,诱发自闭症(ASD)小鼠核心症状的机制.方法 将C57小鼠按照完全随机设计,分为正常对照组(CON组),ASD模型组(VPA组),溶剂对照组(DMSO组)和Wortmannin抑制剂组(Wortmannin组),10只/组.旷场实验,青年玩耍实验和三箱社交实验评价小鼠的ASD样行为;高尔基染色观察小鼠PFC树突棘密度的变化;Western blot检测小鼠PFC信号通路相关蛋白p-PI3K、PI3K、p-AKT、AKT、p-mTOR、mTOR以及突触相关蛋白PSD95、p-Syn、Syn的表达;免疫荧光染色观察PSD95、p-Syn的变化.结...

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Published in南方医科大学学报 Vol. 42; no. 1; pp. 101 - 107
Main Authors 王菲菲, 王路义, 熊玥, 邓静, 吕明其, 汤博诣, 张潇月, 李英博
Format Journal Article
LanguageChinese
Published 重庆医科大学基础医学院生理学教研室,重庆 400016%重庆医科大学实验教学管理中心,重庆 400016%重庆医科大学临床医学院,重庆 400016 2022
Subjects
自闭症;树突棘;突触;PI3K/Akt/mTOR;PSD95;Syn
Online AccessGet full text
ISSN1673-4254
DOI10.12122/j.issn.1673-4254.2022.01.12

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Abstract 目的 探讨前额叶皮层(PFC)树突棘及突触发育障碍,诱发自闭症(ASD)小鼠核心症状的机制.方法 将C57小鼠按照完全随机设计,分为正常对照组(CON组),ASD模型组(VPA组),溶剂对照组(DMSO组)和Wortmannin抑制剂组(Wortmannin组),10只/组.旷场实验,青年玩耍实验和三箱社交实验评价小鼠的ASD样行为;高尔基染色观察小鼠PFC树突棘密度的变化;Western blot检测小鼠PFC信号通路相关蛋白p-PI3K、PI3K、p-AKT、AKT、p-mTOR、mTOR以及突触相关蛋白PSD95、p-Syn、Syn的表达;免疫荧光染色观察PSD95、p-Syn的变化.结果 与CON组相比,VPA组小鼠出现了ASD样表型,PFC总的、成熟型树突棘密度减少(P<0.05),未成熟型树突棘密度增加(P<0.01),信号通路相关蛋白p-PI3K/PI3K、p-AKT/AKT和p-mTOR/mTOR表达上调(P<0.05),突触相关蛋白PSD95和p-Syn/Syn表达下调(P<0.01或P<0.001).Wortmannin能改善小鼠ASD样表型,改善树突棘发育,下调PI3K/Akt/mTOR信号通路及上调突触相关蛋白的表达.结论 PI3K/Akt/mTOR信号通路的过度激活和突触相关蛋白PSD95、p-Syn表达降低可能导致VPA诱导的ASD小鼠PFC树突棘损伤和突触发育障碍,最终导致ASD样表型.
AbstractList 目的 探讨前额叶皮层(PFC)树突棘及突触发育障碍,诱发自闭症(ASD)小鼠核心症状的机制.方法 将C57小鼠按照完全随机设计,分为正常对照组(CON组),ASD模型组(VPA组),溶剂对照组(DMSO组)和Wortmannin抑制剂组(Wortmannin组),10只/组.旷场实验,青年玩耍实验和三箱社交实验评价小鼠的ASD样行为;高尔基染色观察小鼠PFC树突棘密度的变化;Western blot检测小鼠PFC信号通路相关蛋白p-PI3K、PI3K、p-AKT、AKT、p-mTOR、mTOR以及突触相关蛋白PSD95、p-Syn、Syn的表达;免疫荧光染色观察PSD95、p-Syn的变化.结果 与CON组相比,VPA组小鼠出现了ASD样表型,PFC总的、成熟型树突棘密度减少(P<0.05),未成熟型树突棘密度增加(P<0.01),信号通路相关蛋白p-PI3K/PI3K、p-AKT/AKT和p-mTOR/mTOR表达上调(P<0.05),突触相关蛋白PSD95和p-Syn/Syn表达下调(P<0.01或P<0.001).Wortmannin能改善小鼠ASD样表型,改善树突棘发育,下调PI3K/Akt/mTOR信号通路及上调突触相关蛋白的表达.结论 PI3K/Akt/mTOR信号通路的过度激活和突触相关蛋白PSD95、p-Syn表达降低可能导致VPA诱导的ASD小鼠PFC树突棘损伤和突触发育障碍,最终导致ASD样表型.
Author 张潇月
邓静
李英博
熊玥
吕明其
王路义
王菲菲
汤博诣
AuthorAffiliation 重庆医科大学基础医学院生理学教研室,重庆 400016%重庆医科大学实验教学管理中心,重庆 400016%重庆医科大学临床医学院,重庆 400016
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LI Yingbo
ZHANG Xiaoyue
WANG Luyi
TANG Boyi
XIONG Yue
WANG Feifei
DENG Jing
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Title 树突棘及突触发育障碍诱发自闭症小鼠核心症状的机制
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