Histone modification in activated microglia during ischemic stroke

Abstract

Event Abstract Back to Event Histone modification in activated microglia during ischemic stroke Radhika Patnala1, Thiruma Arumugam2 and S. Thameem Dheen1* 1 National University of Singapore, Department of Anatomy, Yong Loo Lin School of Medicine, Singapore 2 National University of Singapore, Department of Physiology, Yong Loo Lin School of Medicine, Singapore Stroke pathogenesis is influenced by the microglia-mediated inflammatory response in the brain. While, healthy microglia are involved in surveillance and protection of the brain, a chronic activation of microglia, as seen in ischemic stroke, aggravates neuropathology and neurotoxicity. Hence, understanding the molecular and epigenetic mechanisms of microglial activation will aid in development of therapeutic strategies that mitigate microglia-mediated neurotoxicity in neuropathologies including ischemic stroke. In this study, we analysed the epigenetic regulation, in particular, the histone modification Histone 3-lysine 9-acetylation (H3K9ac), and its involvement in microglial activation in response to ischemia. H3K9ac has been found to be upregulated in microglia in the peri-infarct and infarct zones after ischemic stroke. The H3K9ac upregulation in microglia in response to 1 hr ischemia with 24hr reperfusion was observed in different regions of the brain. A similar upregulation was observed in lipopolysaccharide (LPS)-activated microglia in the adult rat brain, indicating that the H3K9ac upregulation is consistently associated with microglial activation. It is well established that Histone Deacetylases (HDAC) regulate H3K9ac. In this study, HDAC inhibition altered H3K9ac enrichment and transcription at pro-inflammatory (TNF-alpha, iNOS, STAT 1, IL6) and anti-inflammatory (STAT3 and IL-10) gene promoters in activated microglia in vitro. In the ischemic stroke animal model, HDAC inhibitors were found to downregulate TNF-alpha and iNOS expression in activated microglia, up-regulate IL10 expression and improve neuronal survival, indicating the neuroprotective ability of HDAC inhibitors via microglia. With the advent of HDAC inhibitors entering clinical trials, this study highlights the potential therapeutic value of HDAC inhibitors in treating microglia-mediated neuroinflammation and neurotoxicity in ischemic stroke. Keywords: Microglia, Stroke, Neuroinflammation, Epigenetic regulation, histone modification Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Symposium 6: Neuron-Glia Crosstalk in Healthy and Diseased Brain Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Patnala R, Arumugam T and Dheen S (2016). Histone modification in activated microglia during ischemic stroke. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00026 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: 26 Jul 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. S. Thameem Dheen, National University of Singapore, Department of Anatomy, Yong Loo Lin School of Medicine, Singapore, Singapore, antstd@nus.edu.sg 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 Radhika Patnala Thiruma Arumugam S. Thameem Dheen Google Radhika Patnala Thiruma Arumugam S. Thameem Dheen Google Scholar Radhika Patnala Thiruma Arumugam S. Thameem Dheen PubMed Radhika Patnala Thiruma Arumugam S. Thameem Dheen 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.