Orexin-A aggravates the impairment of hippocampal neurons caused by intermittent hypoxemia by the OXR-PLCβ1-ERK1/2 pathway. Issue 6 (12th April 2017)

• Record Type: Journal Article
• Authors: Li, Guohua; Tang, Shi; Chi, Heng; Huang, Weiwei; Lu, Shanshan; Lv, Xin; Liu, Xiaomin; Li, Yan; Wang, Yanpeng; Tang, Jiyou
• Is Part Of: NeuroReport. Volume 28:Issue 6(2017)
• Publication Date: 2017-04-12
• Subjects: extracellular signal-regulated kinase 1/2 -- hippocampal neuron -- intermittent hypoxemia -- orexin-A; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000000768
• Languages: English
• ISSNs: 0959-4965

Abstract

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.