title: Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia.
abstract: Global cerebral ischemia (GCI) causes energy deficiency results in excessive release of glutamate from neurons. Astrocytic glutamate transporters play a predominant role in keeping extracellular glutamate concentrations below excitotoxic levels. Glutamate transporter 1 (GLT-1) may account for more than 90% of glutamate uptake in adult forebrain. Preclinical findings implicate that Harmine present neuroprotection effects in a rat model of amyotrophic lateral sclerosis disease, and the beneficial effects were specifically due to up-regulation of GLT-1. However, no experiments have explored the potential of Harmine to provide neuroprotection in the setting of GCI. The current study was designed to determine whether Harmine could attenuate cerebral infarction as well as improve neuronal survival after GCI. Furthermore, to test whether the mechanisms were associated with up-regulating of GLT-1, we used a GLT-1 specific inhibitor dihydrokainate (DHK) and analysis the expression of GLT-1 mRNA and protein in cortex of brain. We also examined whether Harmine treatment affected astrocytes activation via immunofluorescence. Our results showed that post-GCI administration of Harmine could attenuate cerebral infarct volume and decrease neurons death. It also caused significantly elevation of GLT-1 mRNA and protein and remarkably attenuation of astrocyte activation. We provide novel clues in understanding the mechanisms of which Harmine exerts its neuroprotective activity in neurological disorders.
authors.affiliation: Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, PR China.
authors.forename: Piyun
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, PR China. Electronic address: shuyanzhang24k@163.com.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second People' s Hospital of Mudanjiang, Mudanjiang 157000, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Harbin 150081, PR China. Electronic address: lihuawang24k@163.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006247:Harmine / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C493395:Slc1a2 protein, rat; D006247:Harmine; C020889:dihydrokainic acid; D007608:Kainic Acid
keywords: Astrocyte activation; Functional recovery; GCI; GLT-1; Harmine