Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

作     者：Huiyang Wang Yueyang Liu Zhenkun Guo Minghui Cui Peng Pang Jingyu Yang Chunfu Wu Huiyang Wang;Yueyang Liu;Zhenkun Guo;Minghui Cui;Peng Pang;Jingyu Yang;Chunfu Wu

作者机构：Department of PharmacologyShenyang Pharmaceutical UniversityShenyang 110016China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2023年第13卷第5期

页      面：2107-2123页

核心收录：

学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：the Natural Science Foundation of Liaoning Province(LJKQZ2021031 2022-MS-246 China)to Yueyang Liu 

主　　题：Chronic cerebral hypoperfusion Two vessel occlusion White matter Cognitive impairment Oligodendrocyte Myelin sheath Autophagy-lysosomal pathway Mechanistic target of rapamycin 

摘      要：Cognitive impairment caused by chronic cerebral hypoperfusion(CCH)is associated with white matter injury(WMI),possibly through the alteration of ***,the autophagy—lysosomal pathway(ALP)dysfunction in white matter(WM)and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion(2VO).The results showed that cognitive impairment occurred by the 28th day after *** and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd *** the 14th day,abnormal accumulation of autophagy substrate,lysosomal dysfunction,and the activation of mechanistic target of rapamycin(MTOR)pathway were observed in WM,paralleled with mature oligodendrocyte *** indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal *** target the ALP dysfunction,enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1(BECN1)in oligodendrocytes reduced mature oligodendrocyte death,and subsequently alleviated the WMI and cognitive impairment after *** results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO,which was associated with the aggravation of WMI and cognitive *** study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.