Ganglioside deficient mice exhibit altered cholesterogenic genes expression in the hippocampus

Abstract

Event Abstract Back to Event Ganglioside deficient mice exhibit altered cholesterogenic genes expression in the hippocampus Kristina Mlinac1*, Katarina Vajn2, Marija Heffer2 and Svjetlana K. Bognar1 1 School of Medicine University of Zagreb, Croatian Institute for Brain Research, Netherlands 2 School of Medicine, Josip Juraj Strossmayer University of Osijek, Department of Medical Biology, Netherlands Gangliosides are membrane lipids abundant in mammalian central nervous system (CNS) which stabilize the mature CNS by promoting the axon-glia interactions. Cholesterol and gangliosides aggregate into highly organized membrane microdomains - lipid rafts, involved in intercellular communication, membrane trafficking, signal transduction, etc. In this study, the expression of cholesterogenic genes was investigated in two knockout mouse models, Siat8a and Galgt1, whose phenotypes include impaired peripheral nerve regeneration, dysmyelination and axonal degeneration. Siat8a mice lack the enzyme GD3 synthase while Galgt1 mice lack the GM2/GD2 synthase. In consequence, depletion of either the b-series gangliosides (GD3, GD2, GD1b, GT1b) or of complex brain gangliosides replaced by simpler gangliosides (GM3, GD3, O-acetyl-GD3) occurs, respectively. The aim was to see whether changed ganglioside profile has an effect on transcription of selected cholesterogenic genes, which could eventually lead to alteration of cholesterol metabolism and redistribution of the major membrane lipids. Using quantitative real-time PCR (qRT-PCR), the gene expression of 14-alpha demethylase (Cyp51) and brain-specific cholesterol 24-hydroxylase (Cyp46) was analyzed in hippocampi of Siat8a, Galgt1 and matched wild type mice. Siat8a mice showed 2-fold increase in the relative mRNA expression for both Cyp51 and Cyp46 when compared to wild type mice. The change was much more prominent for Galgt1 mice: almost 10-fold change for Cyp51 and even more than 20-fold change for Cyp46. The results indicate that there is a significant alteration of gene expression level for analyzed genes involved in cholesterol biosynthesis as a response to ganglioside depletion. We suggest that altered ganglioside profile, in conjuncture with changed cholesterol metabolism can also lead to alterations in signalling pathways and thus contribute to disturbed neuronal maturation and CNS stability caused by the lack of CNS complex gangliosides. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Cellular neuroscience Citation: Mlinac K, Vajn K, Heffer M and Bognar SK (2010). Ganglioside deficient mice exhibit altered cholesterogenic genes expression in the hippocampus. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00093 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: 22 Apr 2010; Published Online: 22 Apr 2010. * Correspondence: Kristina Mlinac, School of Medicine University of Zagreb, Croatian Institute for Brain Research, Zagreb, Netherlands, kristina.mlinac@mef.hr 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 Kristina Mlinac Katarina Vajn Marija Heffer Svjetlana K Bognar Google Kristina Mlinac Katarina Vajn Marija Heffer Svjetlana K Bognar Google Scholar Kristina Mlinac Katarina Vajn Marija Heffer Svjetlana K Bognar PubMed Kristina Mlinac Katarina Vajn Marija Heffer Svjetlana K Bognar 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.