Pharmacological Characteristics of Rotational Behavior in Hemiparkinsonian Rats Transplanted With Mouse Embryonic Stem Cell-Derived Neurons
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概要
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Embryonic stem (ES) cells have many of the characteristics of an optimal cell source for cell-replacement therapy. Although the usefulness of the in vitro generation of dopamine (DA)-neural precursors from ES cells has been widely discussed, functional recovery in animal models of Parkinson’s disease is not fully understood. In 6-hydroxydopamine-lesioned rats, apomorphine markedly induced contralateral rotation. Apomorphine-induced rotation was significantly reduced by transplantation of neuron-like cells that had differentiated from mouse ES cells using nicotinamide, but not <sc><font size = "-2">L</font></sc>-lysine. In addition, methamphetamine-induced ipsilateral rotation was significantly reduced. On the other hand, picrotoxin did not inhibit apomorphine-induced rotational asymmetry. Fluoxetine alone and fenfluramine alone induced slight contralateral rotation and rotation in both directions, respectively, and these effects were similar in transplanted rats. Although immunoreactivity for tyrosine hydroxylase (TH) was almost completely lost in the ipsilateral striatum in hemiparkinsonian rats, TH immunoreactivity was detected in transplanted cells and sprouting fibers. In contrast, immunoreactivities for γ-aminobutyric acid (GABA) and serotonin (5-HT) neurons were not changed. These results suggest that improvement of rotational behavior may be induced predominantly by transplantation of nicotinamide-treated ES cell-derived DA neurons, rather than by changes in the activities of GABA or 5-HT neural systems, in hemiparkinsonian rats.
著者
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Shimohama Shun
Department Of Neurology Faculty Of Medicine Kyoto University
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Kondo Jun-ichi
Department Of Neurobiology Kyoto Pharmaceutical University
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Gu Yuanjin
Department Of Organ Reconstruction Field Of Clinical Application Institute For Frontier Medical Scie
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Kim Dohoon
Department Of Organ Reconstruction Field Of Clinical Application Institute For Frontier Medical Scie
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Tsuchiya Daiju
Department Of Neurobiology 21st Century Coe Program Kyoto Pharmaceutical University
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Inoue Kazutomo
Department Of Organ Reconstruction Field Of Clinical Application Institute For Frontier Medical Scie
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Sumi Shoichiro
Department Of Gastroenterology And Hepatology Shimane University Faculty Of Medicine
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Inden Masatoshi
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University
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Akaike Akinori
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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Kitamura Yoshihisa
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Japan
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Taniguchi Takashi
Department of Biology, Kyoto Pharmaceutical University
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Akaike Akinori
Department of Neuropharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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