Acute Restraint Stress Augments 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Neurotoxicity via Increased Toxin Uptake into the Brain in C57BL/6 Mice  

作　　者：Yasuhide Mitsumoto Atsushi Mori 

机构地区：[1]Laboratory of Alternative Medicine and Experimental Ther- apeutics, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kana- gawa-machi, Kanazawa, Ishikawa 920-1181, Japan [2]Department of Perioperative Management System, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan

出　　处：《Neuroscience Bulletin》2018年第5期849-853,共5页神经科学通报（英文版）

基　　金：supported by the Specific Research Foundation of Hokuriku University(250100)

摘　　要：As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson＇s disease （PD）. Here, we evaluated the effects of acute restraint stress on striatal dopaminergic terminals and the brain metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahy- dropyridine （MPTP）, which has been widely used for creating a mouse model of PD. Exposure to 2 h of restraint stress immediately after injection of a low dose of MPTP caused a severe loss of striatal dopaminergic terminals as indicated by decreases in the dopamine transporter protein and dopamine levels compared with MPTP administration alone. Both striatal 1-methyl-4-phenylpyridinium ion （MPP＋） and MPTP concentrations were significantly increased by the application of restraint stress. Striatal monoamine oxidase-B, which catalyzes the oxidation of MPTP to MPP＋, was not changed by the restraint stress. Our results indicate that the enhanced striatal dopaminergic terminal loss in the stressed mice is associated with an increase in the transport of neurotoxin into the brain.As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson＇s disease （PD）. Here, we evaluated the effects of acute restraint stress on striatal dopaminergic terminals and the brain metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahy- dropyridine （MPTP）, which has been widely used for creating a mouse model of PD. Exposure to 2 h of restraint stress immediately after injection of a low dose of MPTP caused a severe loss of striatal dopaminergic terminals as indicated by decreases in the dopamine transporter protein and dopamine levels compared with MPTP administration alone. Both striatal 1-methyl-4-phenylpyridinium ion （MPP＋） and MPTP concentrations were significantly increased by the application of restraint stress. Striatal monoamine oxidase-B, which catalyzes the oxidation of MPTP to MPP＋, was not changed by the restraint stress. Our results indicate that the enhanced striatal dopaminergic terminal loss in the stressed mice is associated with an increase in the transport of neurotoxin into the brain.

关 键 词：MPTP MPP＋ Mouse model Restraint stress Dopaminergic neuron DEGENERATION Dopamine transporter Dopamine 

分 类 号：R742.5[医药卫生—神经病学与精神病学]