Microglial activation with reduction in autophagy limits white matter lesions and improves cognitive defects during cerebral hypoperfusion.
Microglial activation plays a vital role in the pathogenesis of white matter lesions (WMLs) during chronic cerebral hypo perfusion. Autophagy has been associated with both microglia survival and cell death. Yet, the role of autophagy during microglial activation in chronic cerebral ischemia is still unknown. We used a chronic cerebral hypoperfusion model by permanent stenosis of bilateral common carotid artery in mice to study microglial activation and autophagy. However, the autophagy inhibitor (3-methyladenine) could attenuate microglial autophagic activation, decrease white matter lesions, and improve working memory during chronic cerebral hypoperfusion in mice. In conclusion, chronic cerebral hypoperfusion that leads to microglial activation and autophagy induction exacerbates white matter lesions and cognitive deficits in mice. Our findings represent a potential novel target for chronic cerebral hypoperfusion therapy.
Zhao
Z
Yang
Nan
N
Zhang
Hanchao
H
Shen
Chuangan
C
Lin
Li
L
Lin
Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China. ytt83812280@sina.com.
Bangqing
B
Yuan
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D016893:Carotid Stenosis / Q000150:complications*; D003072:Cognition Disorders / Q000209:etiology* / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D013997:Time Factors; D066127:White Matter / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure
D016207:Cytokines; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C025946:3-methyladenine; D000225:Adenine