Repetitive acute intermittent hypoxia increases neurotrophic and growth factor expression in non‐respiratory motor neurons

Abstract

Repetitive acute intermittent hypoxia (AIH) elicits respiratory motor plasticity and increases growth/trophic factor expression in respiratory motor neurons (Satriotomo et al., 2007; Dale et al., 2007). Here, we tested the hypothesis that repetitive AIH similarly affects neurons involved in non‐respiratory motor behaviors. Growth/trophic factor protein levels were examined via immunofluorescence in sections from perfused rats exposed to thrice weekly AIH (3xwAIH; 10 episodes,10.5% O2, 5 min duration, 5 min interval, 3x per week, 10 weeks). Upper motor‐neurons of primary and secondary motor cortex (M1‐M2) and alpha motor neurons in the cervical (C7) and lumbar (L3‐4) ventral horns were investigated. Compared to sham rats, neurons in all three areas exhibited increased expression of: 1) brain derived neurotrophic factor (BDNF) and its high affinity receptor (TrkB); 2) vascular endothelial growth factor (VEGF) and VEGF receptor‐2; and 3) an important VEGF gene regulator, hypoxia‐inducible factor‐1α. Thus, 3xwAIH regulates endogenous levels of important growth/trophic factors critical for motor neuron survival and plasticity, even in regions of the CNS associated with somatic (versus respiratory) motor control. 3xwAIH may be a useful tool in the treatment of disorders leading to partial paralysis, including spinal injury and motor neuron disease.(NIH HL080209 and NS057778).