Effects of prolyl-hydroxylase inhibition and chronic intermittent hypoxia on synaptic transmission and plasticity in the rat CA1 and dentate gyrus

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Title: Effects of prolyl-hydroxylase inhibition and chronic intermittent hypoxia on synaptic transmission and plasticity in the rat CA1 and dentate gyrus
Authors: Wall, Audrey M.
Corcoran, Alan
O'Halloran, Ken D.
O'Connor, J. J.
Permanent link: http://hdl.handle.net/10197/4791
Date: Feb-2014
Online since: 2013-10-22T08:27:13Z
Abstract: Chronic intermittent hypoxia (CIH) is an underlying component of obstructive sleep apnoea and has been shown to have deleterious and damaging effects on central neurons and to impair synaptic plasticity in the CA1 region of the rat hippocampus.  CIH is a potent inducer of hypoxia inducible factor (HIF), a key regulator in a cell's adaptation to hypoxia that plays an important role in the fate of neurons during ischemia. Levels of HIF-1α are regulated by the activity of a group of enzymes called HIF-prolyl 4-hydroxylases (PHDs) and these have become potential pharmalogical targets for preconditioning against ischemia.  However, little is known about the effects of prolyl hydroxylase inhibition and CIH on synaptic transmission and plasticity in sub-regions of the hippocampus.  Male Wistar rats were treated for 7-days with either saline, CIH or PHD inhibition (dimethyloxaloylglycine, DMOG; 50mg/kg, i.p.). At the end of treatment all three groups showed no change in synaptic excitability or paired pulse paradigms.  However long-term potentiation (LTP) was impaired in the CA1 region of the hippocampus of both CIH and DMOG treated animals.  LTP induced in the dentate gyrus was not significantly affected by CIH or DMOG treatment. We also investigated the effect of 7-day CIH and DMOG treatment on the recovery of synaptic transmission following an acute 30 min hypoxic insult.  CIH treated animals showed an improved rate of recovery of synaptic transmission  following re-oxygentation in both the CA1 and dentate gyrus. This effect was not seen with 7-day DMOG treatment.  These results suggest that LTP induction in the CA1 region is more sensitive to both CIH and DMOG treatment than the dentate gyrus.
Type of material: Journal Article
Publisher: Elsevier
Journal: Neurobiology of Disease
Volume: 62
Issue: February 2014
Start page: 8
End page: 17
Copyright (published version): 2013 Published by Elsevier Inc.
Keywords: Chronic intermittent hypoxia (CIH)Long term potentiation (LTP)Cornu ammons 1 (CA1)Dentate gyrus (dentate gyrus)Dimethyloxaloylglycine (DMOG)Prolyl hydroxylase domain (PHD)Hypoxia inducible factor 1 alpha
DOI: 10.1016/j.nbd.2013.08.016
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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