Brain-derived Neurotrophic Factor Rescues and Prevents Chronic Intermittent Hypoxia-Induced Impairment of Hippocampal Long-Term Synaptic Plasticity

Neurobiol Dis. 2010 Oct;40(1):155-62. doi: 10.1016/j.nbd.2010.05.020. Epub 2010 May 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / administration & dosage
  • Brain-Derived Neurotrophic Factor / therapeutic use*
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / physiopathology
  • Disease Models, Animal
  • Down-Regulation / physiology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Hypoxia, Brain / metabolism
  • Hypoxia, Brain / physiopathology
  • Hypoxia, Brain / prevention & control*
  • Long-Term Potentiation / physiology*
  • Male
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Memory Disorders / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / physiology*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use
  • Organ Culture Techniques
  • Sleep Apnea, Obstructive / metabolism
  • Sleep Apnea, Obstructive / physiopathology
  • Synapses / physiology*

Substances

  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents