title: Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons.
abstract: Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10weeks (3×wAIH). 3×wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3×wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA. Electronic address: satriotomo@ufl.edu.
authors.forename: I
authors.initials: I
authors.lastname: Satriotomo
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Nichols
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Dale
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Emery
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Dahlberg
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002574:Cervical Vertebrae; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D008159:Lumbar Vertebrae; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020813:Receptor, trkB
keywords: BDNF; HIF-1; TrkB; VEGF; intermittent hypoxia; motor neuron