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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

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Abstract

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-tetrahydropyridine (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.

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Acknowledgements

This work was supported by the Specific Research Foundation of Hokuriku University (250100).

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Authors and Affiliations

  1. Laboratory of Alternative Medicine and Experimental Therapeutics, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa, Ishikawa, 920-1181, Japan

    Yasuhide Mitsumoto

  2. Department of Perioperative Management System, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Atsushi Mori

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  1. Yasuhide Mitsumoto
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  2. Atsushi Mori
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Correspondence to Yasuhide Mitsumoto.

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Mitsumoto, Y., Mori, A. 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. Neurosci. Bull. 34, 849–853 (2018). https://doi.org/10.1007/s12264-018-0254-2

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