title: Blunted inflammation mediated by NF-κB activation in hippocampus alleviates chronic normobaric hypoxia-induced anxiety-like behavior in rats.
abstract: This study aims to investigate whether inflammation mediated by NF-κB activation is involved in the induction of anxiety-like behavior in chronic normobaric hypoxia (CNH) exposed rats and to investigate the underlying mechanism. To this end, rats were exposed in a normobaric hypoxic chamber with a fraction of inspired oxygen (FIO2) of ∼ 10%, 23 h/d, continues for 2 weeks. Anxiety-like behavior was tested by elevated plus maze and open field, inflammatory response, nucleus translocation of NF-κB, and signaling pathway in hippocampus were examined. CNH induced a significant increase of anxiety- like behavior and inflammation responses, which were ameliorated by NF-κB inhibitor, PDTC pretreatment, suggesting that the anxiogenic effect induced by inflammation is through NF-κB activation. CNH treatment significantly increased nucleus translocation of p65 and p105 in hippocampus, which was suppressed by PDTC pretreatment. In addition, CNH treatment significantly increased Iba-1, iNOS, COX-2, and p-PKA in hippocampus, which were blocked by PDTC pretreatment, suggesting CNH may activate microglia cells in hippocampus through NF-κB pathway. In conclusion, our results illustrate a mechanism that, activation of NF-κB in hippocampus may trigger the proinflammatory response of microglia cells, and iNOS-PKA pathway may involve in anxiogenic effect in CNH exposed rats.
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Junming
authors.initials: J
authors.lastname: Fan
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Fan
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Guo
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Xia
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ding
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Shouting
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Lianggang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: fxbwzmc@126.com.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000523:psychology; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2
keywords: Anxiety-like behavior; Cytokines; Hypoxia; Inflammation; Nuclear factor-κB