PMID- 22936120 OWN - NLM STAT- MEDLINE DCOM- 20130611 LR - 20211021 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 37 IP - 12 DP - 2012 Dec TI - Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3K/Akt signaling pathway. PG - 2777-86 LID - 10.1007/s11064-012-0871-5 [doi] AB - Many studies have demonstrated that apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Neuroprotective effect of quercetin has been shown in a variety of brain injury models including ischemia/reperfusion. It is not clear whether BDNF-TrkB-PI3K/Akt signaling pathway mediates the neuroprotection of quercetin, though there has been some reports on the quercetin increased brain-derived neurotrophic factor (BDNF) level in brain injury models. We therefore first examined the neurological function, infarct volume and cell apoptosis in quercetin treated middle cerebral artery occlusion (MCAO) rats. Then the protein expression of BDNF, cleaved caspase-3 and p-Akt were evaluated in either the absence or presence of PI3K inhibitor (LY294002) or tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) by immunohistochemistry staining and western blotting. Quercetin significantly improved neurological function, while it decreased the infarct volume and the number of TdT mediated dUTP nick end labeling positive cells in MCAO rats. The protein expression of BDNF, TrkB and p-Akt also increased in the quercetin treated rats. However, treatment with LY294002 or K252a reversed the quercetin-induced increase of BDNF and p-Akt proteins and decrease of cleaved caspase-3 protein in focal cerebral ischemia rats. These results demonstrate that quercetin can decrease cell apoptosis in the focal cerebral ischemia rat brain and the mechanism may be related to the activation of BDNF-TrkB-PI3K/Akt signaling pathway. FAU - Yao, Rui-Qin AU - Yao RQ AD - Department of Neurobiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002 Jiangsu, People's Republic of China. wenxi_yao@163.com FAU - Qi, Da-Shi AU - Qi DS FAU - Yu, Hong-Li AU - Yu HL FAU - Liu, Jing AU - Liu J FAU - Yang, Li-Hua AU - Yang LH FAU - Wu, Xiu-Xiang AU - Wu XX LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120831 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 9IKM0I5T1E (Quercetin) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Blotting, Western MH - Brain Ischemia/enzymology/metabolism/*pathology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Quercetin/*pharmacology MH - Rats MH - Receptor, trkB/*metabolism MH - Signal Transduction/*drug effects EDAT- 2012/09/01 06:00 MHDA- 2013/06/12 06:00 CRDT- 2012/09/01 06:00 PHST- 2012/06/03 00:00 [received] PHST- 2012/08/11 00:00 [accepted] PHST- 2012/07/31 00:00 [revised] PHST- 2012/09/01 06:00 [entrez] PHST- 2012/09/01 06:00 [pubmed] PHST- 2013/06/12 06:00 [medline] AID - 10.1007/s11064-012-0871-5 [doi] PST - ppublish SO - Neurochem Res. 2012 Dec;37(12):2777-86. doi: 10.1007/s11064-012-0871-5. Epub 2012 Aug 31.