Effects of daily acute intermittent hypoxia on 5‐HT2A, BDNF, TrkB and VEGF mRNA expression in rat ventral cervical spinal cord

Phrenic long‐term facilitation (LTF) following acute intermittent hypoxia is a form of serotonin‐dependent respiratory plasticity that requires serotonin 2A (5‐HT2A) receptor activation, new BDNF synthesis and activation of its high affinity receptor, TrkB (Baker‐Herman et al ., Nature Neurosci , 2004). Preconditioning with intermittent hypoxia enhances LTF, an example of respiratory metaplasticity, although the molecular mechanisms underlying enhanced LTF are unclear. We tested the hypothesis that daily acute intermittent hypoxia (dAIH; 10, 5‐min episodes of 10.5% O 2 , 7 days) induces mRNA expression of the same proteins necessary for LTF, particularly the 5‐HT2A receptor, BDNF and TrkB. We also investigated mRNA changes for vascular endothelial growth factor (VEGF), a hypoxia‐induced trophic factor expressed in phrenic motoneurons (Dale et al., ibid ). In preliminary experiments, adult male rats were treated with dAIH (n=2) or normoxia (n=2) and ventral spinal tissue (C4‐C5) containing the phrenic motor nucleus was analyzed for mRNA with qRT‐PCR. Values are reported as the average fold change per well relative to normoxia rats. dAIH increased BDNF and VEGF mRNA (1.9±0.4 and 2.4±0.9 fold, respectively; p<0.05), with a trend towards increased 5‐HT2A mRNA (1.4±0.3, p=0.06). TrkB mRNA was not effected (1.3±0.3, p=0.11). These data suggest that dAIH enhances LTF by up‐regulating the expression of key proteins in its underlying mechanism, and suggest the potential for a role of VEGF in intermittent hypoxia‐induced respiratory plasticity and/or metaplasticity. Supported by NIH HL80209.