Hydroxylase inhibition reduces synaptic transmission and protects against a glutamate-induced ischemia in the CA1 region of the rat hippocampus

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Title: Hydroxylase inhibition reduces synaptic transmission and protects against a glutamate-induced ischemia in the CA1 region of the rat hippocampus
Authors: Batti, Laura
Taylor, Cormac T.
O'Connor, J. J.
Permanent link: http://hdl.handle.net/10197/6484
Date: 2-Jun-2010
Abstract: The discovery of hydroxylases as oxygen sensors and key regulators of hypoxia-induced gene expression has made them a novel target for manipulating the transcriptional response to hypoxia for therapeutic benefit. In this study we have investigated the effect of prolyl hydroxylase inhibition on synaptic activity in hippocampal slices and compared this to the changes occurring following exposure to hypoxia. Furthermore, we investigated a potentially protective role for hydroxylase inhibition against a glutamate-induced ischemic insult in the CA1 region of organotypic hippocampal cultures. Application of the hydroxylase inhibitor, dimethyloxallyl glycine (DMOG), depressed synaptic transmission. Both hypoxia and DMOG induced a reversible reduction in synaptic transmission, enhanced paired pulse facilitation (P<0.05) and inhibited N-methyl d-aspartate receptor (NMDAR) activity (P<0.01). However the effects of DMOG were adenosine A1 receptor independent. Our results also suggest a potential therapeutic application for prolyl 4-hydroxylase (PHD) inhibitors in cerebral ischemia, since DMOG protected the CA1 region in organotypic hippocampal slices against a glutamate-induced ischemic insult.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Copyright (published version): 2010 IBRO
Keywords: Prolyl hydroxylase;Dimethyloxallyl glycine;Hypoxia inducible factor-1 alpha;Hippocampus;Excitatory postsynaptic potential;Paired pulse facilitation
DOI: 10.1016/j.neuroscience.2010.03.011
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection
Medicine Research Collection

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