Hypoxia sensitive genes and respiratory neuroplasticity

Not sure if I understand most of this, the complete dissertation is only 233 pages, so ask your physiatrist for it and what s/he thinks about it.
http://gradworks.umi.com/34/88/3488513.html
Abstract:
Since breathing is essential for life, the neural system controlling breathing must be robust but flexible. One strategy to maintain respiratory homeostasis is adaptive control (i.e. plasticity). One well-known form of respiratory plasticity is phrenic long-term facilitation (pLTF), a persistent enhancement of respiratory nerve output induced by acute exposure to intermittent periods of low oxygen. pLTF is BDNF synthesis-dependent and is one of several pathways that lead to phrenic motor facilitation (pMF). Over longer time periods, cellular responses to hypoxia involve transcriptional regulation of relevant proteins to aid in tissue oxygen delivery. Hypoxia inducible factor (HIF) is a transcription factor responsible for the upregulation of proteins such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO). VEGF was originally known for angiogenesis and EPO was originally described as a hematopoietic factor. However, we now know that both proteins are expressed in the central nervous system where they exert neurotrophic and neuroprotective effects. Since VEGF and EPO signal via cellular cascades similar to BDNF, we wondered if spinal VEGF and EPO receptor activation are also capable of eliciting long-lasting pMF. Thus, we tested the hypotheses that VEGF, EPO, and their receptors are: 1) expressed in the phrenic motor nucleus, the ventral spinal region responsible for motor output to the major inspiratory muscle: the diaphragm, and 2) that VEGF and EPO elicit respiratory motor plasticity in a manner similar to BDNF. We demonstrate that VEGF, VEGFR-2, EPO and EPOR are all located in identified phrenic motor neurons and that acute intrathecal application of these proteins to the cervical spinal cord elicits pMF via a mechanism that requires activity of extracellular-regulated kinases (ERK1/2) and protein kinase B (Akt). Although repetitive exposure to acute intermittent hypoxia (AIH) enhances VEGF receptor expression in phrenic motor neurons, we saw no evidence that VEGF or EPO elicits an enhanced pMF following repetitive AIH. This is the first report of VEGF eliciting plasticity in any motor system, and the first report of EPO eliciting spinal respiratory plasticity. By understanding these mechanisms in detail, the potential exists to "harness" this plasticity for use in patients with chronic ventilatory insufficiency.