Acute hypoxic exposure and prolyl-hydroxylase inhibition improves synaptic transmission recovery time from a subsequent hypoxic insult in rat hippocampus

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Title: Acute hypoxic exposure and prolyl-hydroxylase inhibition improves synaptic transmission recovery time from a subsequent hypoxic insult in rat hippocampus
Authors: O'Connor, J. J.
Lanigan, Sinead
Corcoran, Alan
Mukandala, Gatambwa
Wall, Audrey M.
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Date: 15-Dec-2018 2019-01-07T10:02:28Z
Abstract: In the CNS short episodes of acute hypoxia can result in a decrease in synaptic transmission which may be fully reversible upon re-oxygenation. Stabilization of hypoxia-inducible factor (HIF) by inhibition of prolyl hydroxylase domain (PHD) enzymes has been shown to regulate the cellular response to hypoxia and confer neuroprotection both in vivo and in vitro. Hypoxic preconditioning has become a novel therapeutic target to induce neuroprotection during hypoxic insults. However, there is little understanding of the effects of repeated hypoxic insults or pharmacological PHD inhibition on synaptic signalling. In this study we have assessed the effects of hypoxic exposure and PHD inhibition on synaptic transmission in the rat CA1 hippocampus. Field excitatory postsynaptic potentials (fEPSPs) were elicited by stimulation of the Schaffer collatoral pathway. 30 min hypoxia (gas mixture 95% N2/5% CO2) resulted in a significant and fully reversible decrease in fEPSP slope associated with decreases in partial pressures of tissue oxygen. 15-30 min of hypoxia was sufficient to induce stabilization of HIF in hippocampal slices. Exposure to a second hypoxic insult after 60 min resulted in a similar depression of fEPSP slope but with a significantly greater rate of recovery of the fEPSP. Prior single treatment of slices with the PHD inhibitor, dimethyloxalylglycine (DMOG) also resulted in a significantly greater rate of recovery of fEPSP post hypoxia. These results suggest that hypoxia and ‘pseudohypoxia’ preconditioning may improve the rate of recovery of hippocampal neurons to a subsequent acute hypoxia.
Funding Details: University College Dublin
Type of material: Journal Article
Publisher: Elsevier
Journal: Brain Research
Volume: 1701
Start page: 212
End page: 218
Copyright (published version): 2018 Elsevier
Keywords: Prolyl hydroxylase inhibitionHypoxiaHippocampusCA1 regionSynaptic transmissionPre-conditioning
DOI: 10.1016/j.brainres.2018.09.018
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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