Inhibition of glycogen synthase kinase-3β prevents sympathetic hyperinnervation in infarcted rats

Tsung-Ming Lee, Shinn Zong Lin, Nen Chung Chang

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4 引文 斯高帕斯(Scopus)


We have demonstrated that nerve growth factor (NGF) expression in the myocardium is selectively increased during chronic stage of myocardial infarction, resulting in sympathetic hyperinnervation. Glycogen synthase kinase-3 (GSK-3) signal has been shown to play key roles in the regulation of cytoskeletal assembly during axon regeneration. We assessed whether lithium, a GSK-3 inhibitor, attenuates cardiac sympathetic reinnervation after myocardial infarction through attenuated NGF expression and Tau expression. Twenty-four hours after ligation of the anterior descending artery, male Wistar rats were randomized to either LiCl or SB216763, chemically unrelated inhibitors of GSK-3β, a combination of LiCl and SB216763, or vehicle for four weeks. Myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats compared with sham-operated rats, consistent with excessive sympathetic reinnervation after infarction. Immunohistochemical analysis for sympathetic nerve also confirmed the change of myocardial norepinephrine. This was paralleled by a significant upregulation of NGF protein and mRNA in the vehicle-treated rats, which was reduced after administering either LiCl, SB216763, or combination. Arrhythmic scores during programmed stimulation in the vehicle-treated rats were significantly higher than those treated with GSK-3 inhibitors. Addition of SB216763 did not have additional beneficial effects compared with those seen in rats treated with LiCl alone. Furthermore, lithium treatment increased Tau1 and decreased AT8 and AT180 levels. Chronic use of lithium after infarction, resulting in attenuated sympathetic reinnervation by GSK-3 inhibition, may modify the arrhythmogenic response to programmed electrical stimulation.
頁(從 - 到)979-992
期刊Experimental Biology and Medicine
出版狀態已發佈 - 7月 14 2015

ASJC Scopus subject areas

  • 一般生物化學,遺傳學和分子生物學


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