2015 Fiscal Year Final Research Report
Studies on mechanism of rotenone-induced neurodegeneration in central and peripheral nervous systems and involvement of neuron-astrocyte interaction.
Project/Area Number |
25461279
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Okayama University |
Principal Investigator |
MIYAZAKI IKUKO 岡山大学, 医歯(薬)学総合研究科, 助教 (40335633)
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Co-Investigator(Kenkyū-buntansha) |
ASANUMA MASATO 岡山大学, 大学院医歯薬学総合研究科, 教授 (00273970)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Keywords | パーキンソン病 / ロテノン / アストロサイト / ドパミン神経 / 末梢神経障害 / メタロチオネイン |
Outline of Final Research Achievements |
In this study, we revealed that subcutaneous administration of rotenone caused progressive neurodegeneration in the olfactory bulb and myenteric plexus of ascending colon, in addition to the nigrostriatal pathway, but not in the thoracic cord. Rotenone treatment also induced increases in the number of astrocytes in a time- and region-specific manner. These results suggested that neurodegeneration after rotenone exposure was region-specific, but did not spread retrogradely from the peripheral tissue to nigrostriatal pathway, and that glial activation could be related to rotenone-induced neurotoxicity. Using primary cultured cells, we showed that rotenone induced activation of NFAT, secretion of inflammatory cytokines, and decreased metallothionein release in/from rotenone-treated mesencephalic astrocytes, which caused dopaminergic neurotoxicity. These results suggest possible involvement of glial dysfunction in dopaminergic neurotoxicity induced by environmental toxin rotenone.
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Free Research Field |
神経分子病態学,神経病態薬理学
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