Brain-derived neurotrophic factor rescues and prevents chronic intermittent hypoxia-induced impairment of hippocampal long-term synaptic plasticity

Neurobiology of Disease

卷:40

Ying-Shing Chan¹  Tai-Fai Fok²  Wing-Ho Yung²  Yun-Kwok Wing²  Pak-Cheung Ng³  Ya Ke⁴  Hui Xie⁵  Albert M. Li⁵  Lei Chen⁵  Kin-Ling Leung⁵ 

[1] Department of Physiology, Qingdao University Medical College, Qingdao, China;

[2] Department of Pediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;

[3] Department of Physiology and Research Centre of Heart, Brain Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;

[4] Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;

[5] School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China;

关键词: Intermittent hypoxia;    Sleep apnea;    BDNF;    LTP;    Synaptic plasticity;    Neurotrophic factor;   

DOI  :  

来源: DOAJ

【 摘 要 】

Obstructive sleep apnea (OSA) is a common sleep and breathing disorder characterized by repeated episodes of hypoxemia. OSA causes neurocognitive deficits including perception and memory impairment but the underlying mechanisms are unknown. Here we show that in a mouse model of OSA, chronic intermittent hypoxia treatment impairs both early- and late-phase long-term potentiation (LTP) in the hippocampus. In intermittent hypoxia-treated mice the excitability of CA1 neurons was reduced and hippocampal brain-derived neurotrophic factor (BDNF) was down-regulated. We further showed that exogenous application of BDNF restored the magnitude of LTP in hippocampal slices from hypoxia-treated mice. In addition, microinjection of BDNF into the brain of the hypoxic mice prevented the impairment in LTP. These data suggest that intermittent hypoxia impairs hippocampal neuronal excitability and reduces the expression of BDNF leading to deficits in LTP and memory formation. Thus, BDNF level may be a novel therapeutic target for alleviating OSA-induced neurocognitive deficits.

【 授权许可】

Unknown