HDAC Inhibitor Sodium Butyrate-Mediated Epigenetic Regulation Enhances Neuroprotective Function of Microglia During Ischemic Stroke
作者： Radhika Patnala , Thiruma V Arumugam , Neelima Gupta , S Thameem Dheen
DOI: 10.1007/S12035-016-0149-Z
关键词:
摘要: Cerebral ischemia leads to neuroinflammation and activation of microglia which further contribute stroke pathology. Understanding regulation microglial will aid in the development therapeutic strategies that mitigate microglia-mediated neurotoxicity neuropathologies, including ischemia. In this study, we investigated epigenetic by studying histone modification 3-lysine 9-acetylation (H3K9ac) its deacetylase (HDAC) inhibitors. vitro analysis activated showed HDAC inhibitor, sodium butyrate (SB), alters H3K9ac enrichment transcription at promoters pro-inflammatory (Tnf-α, Nos2, Stat1, Il6) anti-inflammatory (Il10) genes while inducing expression downstream IL10/STAT3 pathway. an experimental mouse (C57BL/6NTac) model middle cerebral artery occlusion (MCAO), observed SB mediates neuroprotection epigenetically regulating inflammatory response, via downregulating mediators, TNF-α NOS2, upregulating mediator IL10, microglia. Interestingly, levels were found be upregulated distributed cortex, striatum, hippocampus MCAO mice. A similar upregulation was detected lipopolysaccharide (LPS)-activated Wistar rat brain, indicating is consistently associated with vivo. Altogether, these results show evidence inhibition being a promising molecular switch modify behavior from could neuroinflammation.
springer.com
sci-hub.se 参考文章(82)
Ryusuke Koshida, Hisashi Oishi, Michito Hamada, Satoru Takahashi, MafB antagonizes phenotypic alteration induced by GM-CSF in microglia. Biochemical and Biophysical Research Communications. ,vol. 463, pp. 109- 115 ,(2015) , 10.1016/J.BBRC.2015.05.036
Anja Henn, Søren Lund, Maj Hedtjärn, André Schrattenholz, Peter Pörzgen, Marcel Leist, The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation. ALTEX-Alternatives to Animal Experimentation. ,vol. 26, pp. 83- 94 ,(2009) , 10.14573/ALTEX.2009.2.83
Hyeon Ju Kim, Peter Leeds, De-Maw Chuang, The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain Journal of Neurochemistry. ,vol. 110, pp. 1226- 1240 ,(2009) , 10.1111/J.1471-4159.2009.06212.X
Johannes Schindelin, Curtis T. Rueden, Mark C. Hiner, Kevin W. Eliceiri, The ImageJ ecosystem: An open platform for biomedical image analysis Molecular Reproduction and Development. ,vol. 82, pp. 518- 529 ,(2015) , 10.1002/MRD.22489
Kevin N. Couper, Daniel G. Blount, Eleanor M. Riley, IL-10: The Master Regulator of Immunity to Infection Journal of Immunology. ,vol. 180, pp. 5771- 5777 ,(2008) , 10.4049/JIMMUNOL.180.9.5771
Vishnu Kannan, Nieske Brouwer, Uwe-Karsten Hanisch, Tommy Regen, Bart J.L. Eggen, Hendrikus W.G.M. Boddeke, Histone deacetylase inhibitors suppress immune activation in primary mouse microglia. Journal of Neuroscience Research. ,vol. 91, pp. 1133- 1142 ,(2013) , 10.1002/JNR.23221
Ke Shuai, Bin Liu, Regulation of JAK–STAT signalling in the immune system Nature Reviews Immunology. ,vol. 3, pp. 900- 911 ,(2003) , 10.1038/NRI1226
Klemen Strle, Jian-Hua Zhou, Suzanne R Broussard, Homer D Venters, Rodney W Johnson, Gregory G Freund, Robert Dantzer, Keith W Kelley, IL-10 promotes survival of microglia without activating Akt. Journal of Neuroimmunology. ,vol. 122, pp. 9- 19 ,(2002) , 10.1016/S0165-5728(01)00444-1
Vivian Tseveleki, Renee Rubio, Sotiris-Spyros Vamvakas, Joseph White, Era Taoufik, Edwige Petit, John Quackenbush, Lesley Probert, Comparative gene expression analysis in mouse models for multiple sclerosis, Alzheimer's disease and stroke for identifying commonly regulated and disease-specific gene changes. Genomics. ,vol. 96, pp. 82- 91 ,(2010) , 10.1016/J.YGENO.2010.04.004
R. C. Paolicelli, G. Bolasco, F. Pagani, L. Maggi, M. Scianni, P. Panzanelli, M. Giustetto, T. A. Ferreira, E. Guiducci, L. Dumas, D. Ragozzino, C. T. Gross, Synaptic Pruning by Microglia Is Necessary for Normal Brain Development Science. ,vol. 333, pp. 1456- 1458 ,(2011) , 10.1126/SCIENCE.1202529