title: Pretreated duloxetine protects hippocampal CA1 pyramidal neurons from ischemia-reperfusion injury through decreases of glial activation and oxidative stress.
abstract: Duloxetine (DXT), a serotonin/norepinephrine reuptake inhibitor, is widely used for the treatment of major depressive disorders. In the present study, we investigated the neuroprotective effect of pre-treated DXT in the hippocampal CA1 region following transient global cerebral ischemia. Pre-treatment with 40mg/kg DXT protected pyramidal neurons in the CA1 region from ischemia-reperfusion injury. In addition, pre-treatment with DXT reduced ischemia-induced activations of microglia and astrocytes in the ischemic CA1 region. On the other hand, we found that pre-treatment with DXT did not increase 4-hydroxy-2-noneal (a marker for lipid peroxidation) and significantly increased the expression of Cu, Zn-superoxide dismutase, an antioxidant, in the CA1 pyramidal neurons compared with non-treated those after ischemia-reperfusion. These results indicate that pre-treated DXT has neuroprotective effect against transient global cerebral ischemia and suggest that the neuroprotective effect of DXT may be due to the attenuation of ischemia-induced glial activation as well as the decrease of oxidative stress.
authors: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Tae-Kyeong
authors: TK
authors: Lee
authors: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea.
authors: Joon Ha
authors: JH
authors: Park
authors: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea.
authors: Ji Hyeon
authors: JH
authors: Ahn
authors: Department of Emergency Medicine and Institute of Medical Sciences, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Myoung Cheol
authors: MC
authors: Shin
authors: Department of Emergency Medicine and Institute of Medical Sciences, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Jun Hwi
authors: JH
authors: Cho
authors: Department of Pediatrics, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chunchen 24253, South Korea.
authors: Eun Joo
authors: EJ
authors: Bae
authors: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Young-Myeong
authors: YM
authors: Kim
authors: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea. Electronic address: mhwon@kangwon.ac.kr.
authors: Moo-Ho
authors: MH
authors: Won
authors: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, South Korea. Electronic address: anaphy@dankook.ac.kr.
authors: Choong-Hyun
authors: CH
authors: Lee
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology*; D005849:Gerbillinae; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000494:pharmacology; D000072105:Superoxide Dismutase-1 / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000068736:Duloxetine Hydrochloride; D000072105:Superoxide Dismutase-1
keywords: Delayed neuronal death; Duloxetine; Glial activation; Oxidative stress; Pyramidal neurons; Transient global cerebral ischemia