title: Neuroprotection and reduced gliosis by atomoxetine pretreatment in a gerbil model of transient cerebral ischemia.
abstract: Atomoxetine (ATX) is a non-stimulant selective norepinephrine reuptake inhibitor that is widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). In this study, we firstly examined neuroprotective effects of pre- or post-treatment with 15 and 30 mg/kg ATX against ischemic damage in the gerbil hippocampal cornus ammonis 1 (CA1) region subjected to 5 min of transient cerebral ischemia using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluoro-J B histofluorescence staining. We found that only pre-treatment with 30 mg/kg ATX protected CA1 pyramidal neurons from ischemic insult. In addition, pre-treatment with 30 mg/kg ATX, which had neuroprotective effect against ischemic damage, distinctly attenuated the activation of astrocytes and microglia in the ischemic CA1 region compared with the vehicle-treated ischemia group by glial fibrillary acidic protein (for astrocytes) and ionized calcium-binding adapter molecule 1 (for microglia) immunohistochemistry. In brief, our present results indicate that ATX has neuroprotective effect against transient cerebral ischemic insult and that the neuroprotective effect of ATX may be closely associated with attenuated glial activation.
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon 24252, South Korea.
authors.forename: Bich Na
authors.initials: BN
authors.lastname: Shin
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon 24252, South Korea.
authors.forename: Bai Hui
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Jeong-Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, 31116, South Korea.
authors.forename: Choong-Hyun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon 24252, South Korea.
authors.forename: Yun Lyul
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Dongtan Sacred Heart Hospital, School of Medicine, Hallym University, Hwaseong 18450, South Korea. Electronic address: pedkimsk@gmail.com.
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea. Electronic address: mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000069445:Atomoxetine Hydrochloride / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005452:Fluoresceins / Q000378:metabolism; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology* / Q000517:prevention & control*; D002546:Ischemic Attack, Transient / Q000150:complications*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism
chemical_list: D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; C435731:fluoro jade; D000069445:Atomoxetine Hydrochloride; D010751:Phosphopyruvate Hydratase
keywords: Atomoxetine; Glial activation; Hippocampus; Neuroprotection; Selective norepinephrine reuptake inhibitor; Transient cerebral ischemia