Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/134941
Title: EPIGENETIC REGULATION OF MICROGLIAL ACTIVATION VIA MODULATION OF HISTONE 3 LYSINE 9 ACETYLATION IN A RODENT MODEL OF ISCHEMIC STROKE
Authors: RADHIKA PATNALA
Keywords: Microglia, Epigenetics, H3K9ac, Ischemia, HDACs, Neuroinflammation
Issue Date: 19-Aug-2016
Source: RADHIKA PATNALA (2016-08-19). EPIGENETIC REGULATION OF MICROGLIAL ACTIVATION VIA MODULATION OF HISTONE 3 LYSINE 9 ACETYLATION IN A RODENT MODEL OF ISCHEMIC STROKE. ScholarBank@NUS Repository.
Abstract: Cerebral Ischemia leads to microglial activation which can resolve post-ischemic pathology. However, chronic activation of microglia, as seen during reperfusion, worsens disease progression. A better understanding of epigenetic mechanisms regulating microglial activation will aid in mitigating microglia-mediated neurotoxicity in ischemia. In this study, we investigated histone modification Histone 3-Lysine 9-acetylation (H3K9ac) and its regulation via Histone deacetylase (HDAC) inhibitors in an experimental mouse model of middle cerebral artery occlusion (MCAO). HDAC inhibitor mediates neuroprotection by epigenetically regulating the microglial inflammatory response. Following MCAO, HDAC inhibition by sodium butyrate (SB) downregulated expression of pro-inflammatory mediators TNF-α and NOS2 in activated microglia, upregulated their anti-inflammatory IL10 expression, and improved neuronal survival. SB altered H3K9ac enrichment and transcription at pro-and anti-inflammatory gene promoters in vitro, while inducing the IL10/STAT3 anti-inflammatory pathway. Altogether, these results provide evidence of HDAC inhibition being a promising molecular switch to epigenetically modify microglial behaviour to alleviate microglia-mediated neurotoxicity.
URI: http://scholarbank.nus.edu.sg/handle/10635/134941
Appears in Collections:Ph.D Theses (Open)

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