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||Online since:||2015-04-14T11:42:15Z||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||Journal:||Neuroscience||Volume:||167||Issue:||4||Start page:||1014||End page:||1024||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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