title: Resveratrol provides neuroprotection by inhibiting phosphodiesterases and regulating the cAMP/AMPK/SIRT1 pathway after stroke in rats.
abstract: Dysfunction of energy metabolism can be a significant and fundamental pathophysiological basis for strokes. In studies of both humans and rodents, resveratrol, a natural polyphenol, has been reported to provide protection from cerebral ischemic injury by regulating expression of silent mating type information regulation 2 homolog 1 (SIRT1). However, direct evidence demonstrating that resveratrol exerts neuroprotection from cerebral ischemia injury by decreasing energy consumption is still lacking. Therefore, the aim of this study was to elucidate the mechanisms and signaling pathways through which resveratrol regulates energy metabolism in the ischemic brain, and to identify potential targets of resveratrol. ATP levels in brain tissues were detected by high performance liquid chromatography. SIRT1 and the phosphorylation of adenosine-monophosphate-activated protein kinase (P-AMPK) expressiones were evaluated by western blot. Levels of phosphodiesterase (PDEs) and cAMP were quantitated by real-time PCR and ELISA, respectively. Results showed that resveratrol significantly reduced the harmful effects of cerebral ischemic injury in vivo. Moreover, levels of ATP, p-AMPK, SIRT1, and cAMP were increased by resveratrol and PDE inhibitors. In conclusion, our findings indicate that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia.
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wan
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yehan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yongying
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ruihang
authors.initials: R
authors.lastname: Hou
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. Electronic address: yxf1960@126.com.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Ye
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000627:therapeutic use*; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D013267:Stilbenes; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D055372:AMP-Activated Protein Kinases; D010727:Phosphoric Diester Hydrolases; D056564:Sirtuin 1; D020889:Rolipram; D000077185:Resveratrol
keywords: AMPK; ATP; PDEs; Resveratrol; SIRT1; Stroke