title: Ecophysiology of neuronal metabolism in transiently oxygen-depleted environments: evidence that GABA is accumulated pre-synaptically in the cerebellum.
abstract: Interactions between coral reef topography, tide cycles, and photoperiod provided selection pressure for adaptive physiological changes in sheltered hypoxic niches to be exploited by specialized tropical reef fish. The epaulette shark Hemiscyllium ocellatum withstands cyclic hypoxia in its natural environment, many hours of experimental hypoxia, and anoxia for up to 5h. It shows neuronal hypometabolism in response to 5% oxygen saturation. Northern-hemisphere hypoxia- and anoxia-tolerant vertebrates that over-winter under ice alter their inhibitory to excitatory neurotransmitter balance to forestall brain ATP depletion in the absence of oxidative phosphorylation. GABA immunochemistry, HPLC analysis and receptor binding studies in H. ocellatum cerebellum revealed a heterogeneous regional accumulation of neuronal GABA despite no change in its overall concentration, and a significant increase in GABA(A) receptor density without altered binding affinity. Increased GABA(A) receptor density would protect the cerebellum during reoxygenation when transmitter release resumes. While all hypoxia- and anoxia-tolerant teleosts examined to date respond to low oxygen levels by elevating brain GABA, the phylogenetically older epaulette shark did not, suggesting that it uses an alternative neuroprotective mechanism for energy conservation. This may reflect an inherent phylogenetic difference, or represent a novel ecophysiological adaptation to cyclic variations in the availability of oxygen.
authors.affiliation: Hypoxia and Ischemia Research Unit, School of Physiotherapy and Exercise Science, Griffith University Gold Coast Campus, Southport 4222, Australia. g.renshaw@griffith.edu.au <g.renshaw@griffith.edu.au>
authors.forename: G M C
authors.initials: GM
authors.lastname: Renshaw
authors.forename: G
authors.initials: G
authors.lastname: Wise
authors.forename: P R
authors.initials: PR
authors.lastname: Dodd
mesh_terms: D000064:Acclimatization; D000818:Animals; D002531:Cerebellum / Q000378:metabolism* / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D004734:Energy Metabolism; D005442:Flumazenil / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000378:metabolism; D012754:Sharks / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D010100:Oxygen