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

Files in This Item:
File Description SizeFormat 
NeuroBiolDis.pdf5.53 MBAdobe PDFDownload
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
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
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:Biomolecular and Biomedical Science Research Collection

Show full item record

SCOPUSTM   
Citations 20

12
Last Week
0
Last month
checked on Jun 23, 2018

Page view(s) 50

78
checked on May 25, 2018

Download(s) 20

278
checked on May 25, 2018

Google ScholarTM

Check

Altmetric


This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.