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Alpha1-adrenergic receptor antagonist tamsulosin ameliorates aging-induced memory impairment by enhancing neurogenesis and suppressing apoptosis in the hippocampus of old-aged rats

Animal Cells and Systems 2017년 21권 6호 p.404 ~ 411
김성은, 한진희, 고일규, 김장주, 김계환,
소속 상세정보
김성은 ( Kim Sung-Eun ) - Kyung Hee University College of Medicine Department of Physiology
한진희 ( Han Jin-Hee ) - Kyung Hee University College of Medicine Kyung Hee Medical Center Department of Anesthesiology and Pain Medicine
고일규 ( Ko Il-Gyu ) - Kyung Hee University College of Medicine Department of Physiology
김장주 ( Kim Chang-Ju ) - Kyung Hee University College of Medicine Department of Physiology
김계환 ( Kim Khae-Hawn ) - Gachon University Gil Medical Center Department of Urology

Abstract


Age-related memory decline is closely associated with decreased neurogenesis and increased apoptosis in the hippocampus. Noradrenaline exerts its effect by selectively binding to and activating adrenergic receptors (ARs). Tamsulosin, α1-AR antagonist, is reported to have access to the brain and interact with α1-AR. In this study, the effects of tamsulosin on short-term and spatial learning memory in terms of neurogenesis and apoptosis were investigated using rats. Step-down avoidance test for short-term memory and radial 8-arm maze test for spatial learning memory were conducted. Neurogenesis was detected by 5-bromo-2’-deoxyuridine (BrdU) immunohistochemistry and apoptosis was evaluated by caspase-3 immunohistochemisty and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNE) staining. Western blot for protein kinase C (PKC), cAMP-responsive element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), phosphatidylinositol 3-kinase (PI 3-kinase), Akt, Bcl-2, and Bax was conducted. In the aged rats, short-term and spatial learning memory was declined. Hippocampal nerogenesis was suppressed and hippocampal apoptosis was enhanced in the aged rats. In addition, phosphorylation of PKCα, CREB, PI-3 kinase, and Akt was decreased in the hippocampus of old-aged rats. Tamsulosin activated PKC/CREB and PI-3 kinase/Akt pathways. With these pathways, BDNF-TrkB signaling enhanced hippocampal neurogenesis and suppressed apoptosis in the old-aged rats. As the results, tamsulosin improved performance of short-term and spatial learning memory in the aged rats.

키워드

Tamsulosin; aging; adrenergic receptor; memory; hippocampus

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