Depression-like behaviour of MOAP-1-/- mice - altered serotonergic mechanisms

Abstract

Event Abstract Back to Event Depression-like behaviour of MOAP-1-/- mice - altered serotonergic mechanisms Hui Zhao1*, Nur-Ezan Mohamed1, Su Jing Chan1, Victor C. Yu2 and Peter T. Wong1 1 National University of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine,, Singapore 2 National University of Singapore , Department of Pharmacy, Faculty of Science, Singapore Modulator of apoptosis 1 (MOAP-1), as an upstream protein of Bax, plays a key role in mediating Bax function. Bax KO mice have been reported to show depression-like behaviour. Our studies on MOAP-1-/- (KO) mice show that they exhibited similar depression-like behaviour in the force swimming test (FST) and tail suspension test (TST), when compared to wildtype (WT) controls. Here we report new findings that suggest altered serotonergic mechanisms in the MOAP-1 KO mice may underlie the depression-like behaviour. When the mice were subjected to stress in the form of 3 successive daily exposure to water, the level of expression of the tryptophan hydroxylase 2 (TPH2, the rate-limiting enzyme in the biosynthesis of serotonin) protein was significantly lower in the midbrain region of the KO mice when compared to the WT controls. Consistently, the number of TPH2-positive cells in the dorsal raphe nucleus (DRN) were observed to be significantly less in the KO mice using immunofluorescent staining. These results suggest that the KO mice were less able to respond to stress by increases in their central serotonergic activities. In support, we observed decreased plasma serotonin (5-HT) levels in KO mice when compared with WT mice. On the contrary, it is interesting to note that SERT (serotonin transporter), 5-HT1A, and 5-HT2A receptor mRNA expression levels in the midbrain remained unchanged. However, acute treatment with a single dose of the serotonin selective reuptake inhibitor fluoxetine decreased the immobility time (in the FST) of the KO mice, while that of the WT mice remained unchanged. Taken together, our findings strongly suggest that the absence of MOAP-1 in the KO mice resulted in a reduced capacity for the mice to adapt to stress through increases in central serotonergic activities. Keywords: Depression, behaviour, mouse model, midbrain, serotonergic Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Zhao H, Mohamed N, Chan S, Yu VC and Wong PT (2016). Depression-like behaviour of MOAP-1-/- mice - altered serotonergic mechanisms. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00132 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Ms. Hui Zhao, National University of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine,, Singapore, Singapore, Singapore, a0123672@u.nus.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hui Zhao Nur-Ezan Mohamed Su Jing Chan Victor C Yu Peter T Wong Google Hui Zhao Nur-Ezan Mohamed Su Jing Chan Victor C Yu Peter T Wong Google Scholar Hui Zhao Nur-Ezan Mohamed Su Jing Chan Victor C Yu Peter T Wong PubMed Hui Zhao Nur-Ezan Mohamed Su Jing Chan Victor C Yu Peter T Wong Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.