Affiliation:
1. Department of Physiology College of Basic Medical Sciences Liaoning Provincial Key Laboratory of Cerebral Diseases National‐Local Joint Engineering Research Center for Drug‐Research and Development (R & D) of Neurodegenerative Diseases Dalian Medical University Dalian 116044 China
2. Department of Critical Care Medicine the Second Hospital of Dalian Medical University Dalian 116023 China
3. School of Medicine Nanjing University of Chinese Medicine Nanjing 210023 China
Abstract
AbstractThe pathology of sepsis‐associated encephalopathy (SAE) is related to astrocyte‐inflammation associated with aquaporin‐4 (AQP4). The aim here is to investigate the effects of AQP4 associated with SAE and reveal its underlying mechanism causing cognitive impairment. The in vivo experimental results reveal that AQP4 in peripheral blood of patients with SAE is up‐regulated, also the cortical and hippocampal tissue of cecal ligation and perforation (CLP) mouse brain has significant rise in AQP4. Furthermore, the data suggest that AQP4 deletion could attenuate learning and memory impairment, attributing to activation of astrocytic autophagy, inactivation of astrocyte and downregulate the expression of proinflammatory cytokines induced by CLP or lipopolysaccharide (LPS). Furthermore, the activation effect of AQP4 knockout on CLP or LPS‐induced PPAR‐γ inhibiting in astrocyte is related to intracellular Ca2+ level and sodium channel activity. Learning and memory impairment in SAE mouse model are attenuated by AQP4 knockout through activating autophagy, inhibiting neuroinflammation leading to neuroprotection via down‐regulation of Nav1.6 channels in the astrocytes. This results in the reduction of Ca2+ accumulation in the cell cytosol furthermore activating the inhibition of PPAR‐γ signal transduction pathway in astrocytes.
Funder
Natural Science Foundation of Liaoning Province
China Postdoctoral Science Foundation
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
5 articles.
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