title: Orexin-A aggravates the impairment of hippocampal neurons caused by intermittent hypoxemia by the OXR-PLCβ1-ERK1/2 pathway.
abstract: Obstructive sleep apnea is a highly prevalent but under-recognized disorder that causes neurocognitive deficits such as spatial memory and learning deficits. These deficits are frequently accompanied by an increase in orexin-A, which has been shown to be involved in learning and memory as well as in neuronal apoptosis in brain areas involved in cognition, such as the hippocampus. The aim of this work was to study the possible harmful effects of orexin-A on intermittent hypoxemia-induced hippocampal neuronal damage and to investigate the potential underlying molecular mechanisms and signaling pathways in vitro. We established a hypoxia model in cultured rat hippocampal neurons and evaluated the effects of orexin-A by testing the apoptosis rate of the hippocampal neurons. Further studies using the extracellular signal-regulated kinase 1/2 inhibitor U0126, siRNA-PLCβ1, and siRNA-PLCβ4 were carried out to evaluate the mechanisms by which orexin-A contributes toward impairment of hippocampal neurons. The results showed that orexin-A increases intermittent hypoxemia-induced hippocampal neurons damage by overphosphorylating extracellular signal-regulated kinase 1/2 through the OXR-PLCβ1 pathway.
authors.affiliation: aDepartment of Neurology, Qianfoshan Hospital, Shandong University bDepartment of Neurology, Third People's Hospital of Jinan cDepartment of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.forename: Shi
authors.initials: S
authors.lastname: Tang
authors.forename: Heng
authors.initials: H
authors.lastname: Chi
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lu
authors.forename: Xin
authors.initials: X
authors.lastname: Lv
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiyou
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D064446:Orexin Receptors / Q000819:agonists / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism* / Q000633:toxicity; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017208:Rats, Wistar; D020181:Sleep Apnea, Obstructive / Q000378:metabolism
chemical_list: D064446:Orexin Receptors; D000068797:Orexins; D054799:Phospholipase C beta