title: Metformin prevents cerebellar granule neurons against glutamate-induced neurotoxicity.
abstract: Metformin, a wildly used drug for type 2 diabetes, has recently been proven to protect a variety of cells from stress including stroke. Glutamate is an excitatory neurotransmitter that contributes to excitatory neuronal damage involved in stroke and neurodegenerative disorders. In this study, we demonstrated that pretreatment of rat cerebellar granule neurons (CGN) with metformin greatly enhanced cell viability against glutamate-induced neurotoxicity. Metformin significantly attenuated neuronal apoptosis in glutamate-treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases. Our results suggested that metformin was able to directly inhibit glutamate induced excitotoxicity in neurons and might be beneficial to patients suffered from stroke and neurodegenerative disorders.
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Outpatient OR, The 1st Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Acupuncture, Linyi People's Hospital, Linyi 276000, PR China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Zhuang
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Chongyi
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Shitou
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: huiygu@iupui.edu.
authors.forename: Huiying
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China. Electronic address: liu@21cn.com.
authors.forename: Qingpeng
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats
chemical_list: D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D045304:Cytochromes c; D008687:Metformin; D048670:MAP Kinase Kinase 4; D053148:Caspase 3
keywords: Cerebellar granule neurons; Excitotoxicity; Glutamate; MAPK; Metformin; Neuroprotection