Sirt3 Mediates the Inhibitory Effect of Adjudin on Astrocyte Activation and Glial Scar Formation following Ischemic Stroke

Frontiers in Pharmacology
Xiao YangWeiliang Xia

Abstract

In response to stroke-induced injury, astrocytes can be activated and form a scar. Inflammation is an essential component for glial scar formation. Previous study has shown that adjudin, a potential Sirt3 activator, could attenuate lipopolysaccharide (LPS)- and stroke-induced neuroinflammation. To investigate the potential inhibitory effect and mechanism of adjudin on astrocyte activation, we used a transient middle cerebral artery occlusion (tMCAO) model with or without adjudin treatment in wild type (WT) and Sirt3 knockout (KO) mice and performed a wound healing experiment in vitro. Both our in vivo and in vitro results showed that adjudin reduced astrocyte activation by upregulating Sirt3 expression. In addition, adjudin treatment after stroke promoted functional and neurovascular recovery accompanied with the decreased area of glial scar in WT mice, which was blunted by Sirt3 deficiency. Furthermore, adjudin could increase Foxo3a and inhibit Notch1 signaling pathway via Sirt3. Both the suppression of Foxo3a and overexpression of N1ICD could alleviate the inhibitory effect of adjudin in vitro indicating that Sirt3-Foxo3a and Sirt3-Notch1 signaling pathways were involved in the inhibitory effect of adjudin in wound healing ex...Continue Reading

References

Jan 7, 1998·Trends in Neurosciences·J L RidetF H Gage
Apr 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Krishnan SriramJames P O'Callaghan
Nov 23, 2006·Nature Clinical Practice. Neurology·Nicholas J Maragakis, Jeffrey D Rothstein
Aug 5, 2009·The Journal of Clinical Investigation·Nagalingam R SundaresanMahesh P Gupta
Sep 29, 2009·Trends in Neurosciences·Michael V Sofroniew
Feb 5, 2010·Journal of Leukocyte Biology·Rong JinGuohong Li
Jun 15, 2011·Free Radical Biology & Medicine·Tetsuro KoyamaTakashi Uzu
Aug 13, 2011·Stroke; a Journal of Cerebral Circulation·Issei S ShimadaJeffrey L Spees
Apr 19, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yi BaoSunghee Cho
Oct 23, 2012·Journal of Neuroimmunology·Jiaxiang ShaoWeiliang Xia
May 15, 2013·Free Radical Biology & Medicine·Anne H H TsengDanny Ling Wang
Jun 1, 2013·Stroke; a Journal of Cerebral Circulation·Macarena Hernández-JiménezMaría A Moro
Nov 7, 2013·Gerontology·David B Lombard, Bernadette M M Zwaans
Dec 19, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Beatriz Rodriguez-GrandeEmmanuel Pinteaux
Mar 1, 2014·International Journal of Medical Sciences·Lijie HuangKunlin Jin
May 27, 2014·Frontiers in Pharmacology·Caterina ScuderiLuca Steardo
May 31, 2014·Stroke; a Journal of Cerebral Circulation·Yaning LiYongting Wang
Jun 11, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Junxiang YinJiong Shi
Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Matthew D LeComteJeffrey L Spees
Mar 2, 2016·International Journal of Molecular Sciences·Hima Charika S AbeysingheCarli L Roulston
Mar 31, 2016·Nature·Mark A AndersonMichael V Sofroniew
Apr 28, 2016·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Stefanie Robel
Nov 25, 2016·Neurochemical Research·Henryk JęśkoJoanna B Strosznajder
Apr 12, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hongxia CaiZhijun Zhang

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Citations

Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Long-Fang TuRong-Rong He
Nov 30, 2019·Journal of Molecular Neuroscience : MN·Yuanyuan HeZhongying Chen
May 20, 2018·CNS Neuroscience & Therapeutics·Xiao YangWei-Liang Xia
Aug 10, 2018·Frontiers in Cellular Neuroscience·Elena Sidorova-DarmosJames H Eubanks
Mar 3, 2020·Frontiers in Cellular Neuroscience·Ruqayya AfridiKyoungho Suk
Nov 20, 2018·Frontiers in Neuroscience·Joshua M Marcus, Shaida A Andrabi
Feb 14, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Abel Po-Hao HuangShan-Hui Hsu

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Methods Mentioned

BETA
protein assay
electrophoresis
PCR
transfection

Software Mentioned

ImageJ
GraphPad Prism
GraphPad

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