Adenosine monophosphate activated protein kinase inhibition is protective in both sexes after experimental stroke.

Neuroscience Letters
Jun LiLouise D McCullough

Abstract

Sex differences in clinical and experimental stroke are now well recognized. Adenosine monophosphate activated protein kinase (AMPK) is an important energy sensor that is activated in times of energy demand. Increasing AMPK is deleterious in experimental cerebral ischemia, at least in males. Interestingly, studies in peripheral tissues have suggested that there are sex differences in the regulation of AMPK in muscle after exercise. PolyADP ribose polymerase (PARP), a key mediator of ischemic cell death, stimulates AMPK activation, yet activation of PARP appears to be selectively detrimental in male brain. As interference with sex specific cell death pathways can determine the efficacy of experimental neuroprotective agents, and AMPK inhibition is a novel neuroprotective target, we examined the effect of AMPK inhibition in male and female mice. In this study, AMPK alpha2 gene expression (mRNA) and pAMPK protein levels were examined and found to be comparable between both sexes after transient middle cerebral artery occlusion (MCAO). Treatment with the AMPK inhibitor Compound C at stroke onset significantly reduced infarct size and neurological deficits 24h after stroke in ovariectomized female mice. Finally, genetic deletion of ...Continue Reading

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Citations

Jul 9, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Takashi IshiharaMitsuaki Isobe
Mar 4, 2014·Pharmacology & Therapeutics·Sarah E Sinnett, Jay E Brenman
May 26, 2012·Cellular and Molecular Life Sciences : CMLS·Tz-Chuen JuYijuang Chern
Mar 1, 2012·Neuromolecular Medicine·Zhiyou CaiBin Zhao
Jun 30, 2015·Journal of Neurogenetics·Yu-Ju Liu, Yijuang Chern
Jun 12, 2012·Experimental Neurology·Benjamin J WhiteJun Li
May 30, 2012·The European Journal of Neuroscience·Elisabetta GeraceDomenico E Pellegrini-Giampietro
May 6, 2014·The Journal of Spinal Cord Medicine·Byung Moon ChoSeung Myung Moon
Feb 14, 2013·Neuroscience·C S Siegel, L D McCullough
Feb 15, 2017·Nutritional Neuroscience·Narayana Pineda-RamírezPenélope Aguilera
Jul 14, 2012·Experimental Neurobiology·Santosh Ramamurthy, Gabriele Ronnett
Jun 22, 2017·Metabolic Brain Disease·Xiao-Ling DengZhiyou Cai
Mar 11, 2015·Biochemistry. Biokhimii︠a︡·D S NovikovaV G Tribulovich
Jun 11, 2014·Journal of Chemical Information and Modeling·Hwangseo ParkYang-Hee Kim
Sep 29, 2021·The Journal of Clinical Investigation·Louise D McCulloughVenugopal Reddy Venna

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