WIP1 Phosphatase Plays a Critical Neuroprotective Role in Brain Injury Induced by High-Altitude Hypoxic Inflammation  

作　　者：Dahu Li Lijun Zhang Xin Huang Lili Liu Yunling He Lun Xu Yiyao Zhang Tong Zhao Liying Wu Yongqi Zhao Kuiwu Wu Yan Wu Ming Fan Lingling Zhu 

机构地区：[1]Department of Cognitive Science,Institute of Basic MedicalSciences,Beijing 100850,China [2]Co-innovation Center of Neuroregeneration,Nantong University,Nantong 226001,China [3]Beijing Institute for Brain Disorders,Beijing 100069,China [4]Navy General Hospital of the PLA,Beijing 100048,China [5]Air Force General Hospital of the PLA,Beijing 100142,China

出　　处：《Neuroscience Bulletin》2017年第3期292-298,共7页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(31401000 and 81430044);the Youth Medicine Program of the People’s Liberation Army of China(13QNP148);the National Basic Research Development Program(973 Program)of China(2012CB518200);the Integrated Drug Discovery Technology Platform of National Science and Technology Major Projects for‘‘Major New Drugs Innovation and Development’’,China(2012ZX09J12201-005)

摘　　要：The hypobaric hypoxic environment in highaltitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1（WIP1） plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear.Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities. Collectively, these results provide the first in vivo evidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury.The hypobaric hypoxic environment in highaltitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1（WIP1） plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear.Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities. Collectively, these results provide the first in vivo evidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury.

关 键 词：Hypobaric hypoxia Inflammation Brain injury WIP1 phosphatase Lipopolysaccharide 

分 类 号：R741[医药卫生—神经病学与精神病学]