title: HO-1 attenuates hippocampal neurons injury via the activation of BDNF-TrkB-PI3K/Akt signaling pathway in stroke.
abstract: Although recent studies have found that HO-1 plays an important role in neuronal survival, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of HO-1 against ischemic brain injury induced by cerebral I/R and to explore whether the BDNF-TrkB-PI3K/Akt signaling pathway contributed to the protection provided by HO-1. Over-expressed HO-1 plasmids were employed to induce the overexpression of HO-1 through hippocampi CA1 injection 5 days before the cerebral I/R animal model was induced by four-vessel occlusion for 15 min transient ischemia and followed by reperfusion in Sprague-Dawley rats. Immunoblotting was carried out to examine the expression of the related proteins, and HE-staining was used to detect the percentage of living neurons in the hippocampal CA1 region. The results showed that over-expressed HO-1 could significantly protect neurons against cerebral I/R. Furthermore, the protein expression of BDNF, TrkB and p-Akt also increased in the rats treated with over-expressed HO-1 plasmids. However, treatment with tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) reversed the HO-1-induced increase in BDNF and p-Akt protein levels and decreased the level of cleaved caspase-3 protein in I/R rats. In summary, our results imply that HO-1 can decrease cell apoptosis in the I/R rat brain and that the mechanism may be related to the activation of the BDNF-TrkB-PI3K/Akt signaling pathway.
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Dashi
authors.initials: D
authors.lastname: Qi
authors.affiliation: Department of Human anatomy, Xuzhou Medical College, PR China.
authors.forename: Changjie
authors.initials: C
authors.lastname: Ouyang
authors.affiliation: Department of Human anatomy, Xuzhou Medical College, PR China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Human anatomy, Xuzhou Medical College, PR China.
authors.forename: Shichun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xuzhou Central Hospital, PR China.
authors.forename: Xijuan
authors.initials: X
authors.lastname: Ma
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: YuanJian
authors.initials: Y
authors.lastname: Song
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: HongLi
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, PR China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Xuzhou Medical College, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Weihao
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Miao
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Li
authors.affiliation: School of Public Health, Xuzhou Medical College, PR China. Electronic address: 834918590@qq.com.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, PR China; School of Public Health, Xuzhou Medical College, PR China. Electronic address: dhyxzh163@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002227:Carbazoles / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*; D014162:Transfection
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D020813:Receptor, trkB; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Apoptosis; Brain-derived neurotrophic factor (BNDF); HO-1; PI3K/Akt; Stroke; TrkB