Brain-derived neurotrophic factor rescues and prevents chronic intermittent hypoxia-induced impairment of hippocampal long-term synaptic plasticity.
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.
Xie
Hui
H
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Leung
Kin-Ling
KL
Chen
Lei
L
Chan
Ying-Shing
YS
Ng
Pak-Cheung
PC
Fok
Tai-Fai
TF
Wing
Yun-Kwok
YK
Ke
Ya
Y
Li
Albert M
AM
Yung
Wing-Ho
WH
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D009924:Organ Culture Techniques; D020181:Sleep Apnea, Obstructive / Q000378:metabolism / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents