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Effects of prolyl-hydroxylase inhibition and chronic intermittent hypoxia on synaptic transmission and plasticity in the rat CA1 and dentate gyrus
Date Issued
2014-02
Date Available
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.
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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