title: Chronic hypoxia-induced alteration of presynaptic protein profiles and neurobehavioral dysfunction are averted by supplemental oxygen in Lymnaea stagnalis.
abstract: Chronic hypoxia causes neural dysfunction. Oxygen (O(2)) supplements have been commonly used to increase the O(2) supply, yet the therapeutic benefit of this treatment remains controversial due to a lack of cellular and molecular evidence. In this study, we examined the effects of short-burst O(2) supplementation on neural behavior and presynaptic protein expression profiles in a simple chronic hypoxia model of snail Lymnaea stagnalis. We reported that hypoxia delayed the animal response to light stimuli, suppressed locomotory activity, induced expression of stress-response proteins, hypoxia inducible factor-1alpha (HIF-1alpha) and heat shock protein 70 (HSP70), repressed syntaxin-1 (a membrane-bound presynaptic protein) and elevated vesicle-associated membrane protein-1 (VAMP-1) (a vesicle-bound presynaptic protein) level. O(2) supplements relieved suppression of neural behaviors, and corrected hypoxia-induced protein alterations in a dose-dependent manner. The effectiveness of supplemental O(2) was further evaluated by determining time courses for recovery of neural behaviors and expression of stress response proteins and presynaptic proteins after relief from hypoxia conditions. Our findings suggest that O(2) supplement improves hypoxia-induced adverse alterations of presynaptic protein expression and neurobehaviors, however, the optimal level of O(2) required for improvement is protein specific and system specific.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 3306 MSB, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
authors.forename: G-H
authors.initials: GH
authors.lastname: Fei
authors.forename: Z-P
authors.initials: ZP
authors.lastname: Feng
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008195:Lymnaea / Q000166:cytology / Q000378:metabolism*; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D050827:Syntaxin 1 / Q000378:metabolism; D013997:Time Factors; D050987:Vesicle-Associated Membrane Protein 1 / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D050884:HSP72 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050827:Syntaxin 1; D050987:Vesicle-Associated Membrane Protein 1; D010100:Oxygen