Memorial University DAI: The role of the read through variant of acetylcholinesterase in anxiogenic effects of predator stress in mice

advanced search

Digital Archives Initiative
Memorial University - Electronic Theses and Dissertations 4

menu off

add document to favorites : add page to favorites : reference url

back to results : previous : next

Search this object:

0 hit(s) :: previous hit : next hit

View:

previous page : next page

Document Description

Title	The role of the read through variant of acetylcholinesterase in anxiogenic effects of predator stress in mice
Author	Head, David Martin, 1981-
Description	Thesis (M.Sc.)--Memorial University of Newfoundland, 2008. Psychology
Date	2008
Pagination	vii, 67 leaves : ill.
Subject	Acetylcholinesterase--Physiological effect.; Predatory animals--Effect of stress on;
Degree	M.Sc.
Degree Grantor	Memorial University of Newfoundland. Dept. of Psychology
Discipline	Psychology
Language	Eng
Notes	Includes bibliographical references (leaves 39-52)
Abstract	The goal of this study was to examine the role of the read-through variant of acetylcholinesterase (AChE-R) in the changes in affective behaviour using the predator stress model of PTSD. This read through variant has been shown to exist at higher levels in the brain following stress (Pick, Flores-Flores, & Soreq, 2004, Meshorer et al., 2002). -- The role of acetylcholinesterase in predator stress was examined in mice using a novel drug EN 101, a systematically administered central acting antisense mRNA for AChE-R. Research by Pollak at el. (2005) demonstrated that cholinergic enhancement using EN 101 produces central and peripheral anti-inflammatory effects. EN101 acts to disrupt the stress precipitated induction of the transcription of the read-through variant of AChE by selectively targeting the mRNA sequence for AChE-R. It is AChE-R in limbic cholinergic circuitry that contributes to anxiogenic effects of traumatic stress (Talma et al., 2003). We administered multiple injections of the drug to the same animals at specific time points prior to and after a predator stress exposure in male C57 mice. This was done to ascertain whether the specific action of EN 101 on AChE-R expression had any effect on stress induced lasting changes in multiple tests of murine affective behaviour. -- Predator stress caused a significant increase in startle amplitude, which EN 101 blocked. This effect was specific to EN 101, as the control inverse drug INVEN101 was without effect on stress effects on startle amplitude. INVEN101 is the inverse of the EN 101 drug consisting of the same mRNA base pairs only in a different order than EN 101. This evidence suggests that EN101 is acting to lower the levels of the read-through variant of acetylcholinesterase in brain regions responsible for startle amplitude (hyperarousal) in rodents. Neither drug affected the impact of predator stress on behaviour in the plus maze, and both drugs partially reduced stress suppression of time active in the hole board. In the light dark box test INVEN101 appeared to exhibit a weak effect partially inhibiting the effects of predator stress on light dark box behaviour. This behavioural change would require replication in order to accept. Together the data reinforce the supposition that multiple neural systems are responsible for the different changes in behaviour produced by predator stress. -- This study provides evidence for a role of AChE-R in specific changes in anxiety-like behaviour following stress. Further research is necessary to pinpoint the exact time window for administration of the drug in order to prevent or inhibit changes in affective behaviour following predator stress. Work is also needed to determine whether other systemic effects of the drug might occur.
Type	Text
Resource Type	Electronic thesis or dissertation
Format	Image/jpeg; Application/pdf
Source	Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
Local Identifier	a2543867
Rights	The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
Collection	Electronic Theses and Dissertations
Scanning Status	Completed
PDF File	(7.78 MB) -- http://collections.mun.ca/PDFs/theses/Head_DavidM.pdf
CONTENTdm file name	172672.cpd