title: Efficacy of atorvastatin on hippocampal neuronal damage caused by chronic intermittent hypoxia: Involving TLR4 and its downstream signaling pathway.
abstract: Hippocampal neuronal damage is critical for the initiation and progression of neurocognitive impairment accompanied obstructive sleep apnea syndrome (OSAS). Toll-like receptor 4 (TLR4) plays an important role in the development of several hippocampus-related neural disorders. Atorvastatin was reported beneficially regulates TLR4. Here, we examined the effects of atorvastatin on hippocampal injury caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological change of OSAS. Mice were exposed to intermittent hypoxia with or without atorvastatin for 4 weeks. Cell damage, the expressions of TLR4 and its two downstream factors myeloid differentiation factor 88 (MYD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF), inflammatory agents (tumor necrosis factor α and interleukin 1β), and the oxidative stress (superoxide dismutase and malondialdehyde) were determined. Atorvastatin decreased the neural injury and the elevation of TLR4, MyD88, TRIF, pro-inflammatory cytokines and oxidative stress caused by CIH. Our study suggests that atorvastatin may attenuate CIH induced hippocampal neuronal damage partially via TLR4 and its downstream signaling pathway.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Xue-ling
authors.initials: XL
authors.lastname: Guo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Die
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Yue-ying
authors.initials: YY
authors.lastname: Pan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China. Electronic address: hgliu@tjh.tjmu.edu.cn.
authors.forename: Hui-guo
authors.initials: HG
authors.lastname: Liu
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D018696:Neuroprotective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000069059:Atorvastatin; D013482:Superoxide Dismutase
keywords: Atorvastatin; Hippocampus; Intermittent hypoxia; Neuroinflammation; Sleep apnea; Toll-like receptor 4