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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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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 / ドパミン神経細胞 / オートファジー / NFAT |
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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Report
(4 results)
Research Products
(69 results)
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[Journal Article] Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease.2016
Author(s)
Sasaki, T., Liu, K., Agari, T., Yasuhara, T., Morimoto, J., Okazaki, M., Takeuchi, H., Toyoshima, A., Sasada, S., Shinko, A., Kondo, A., Kameda, M., Miyazaki, I., Asanuma, M., Borlongan, C.V., Nishibori, M. and Date, I.
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Journal Title
Exp. Neurol.
Volume: 275
Pages: 220-231
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Doxorubicin and cyclophosphamide treatment produces anxiety-like behavior and spatial cognition impairment in rats: Possible involvement of hippocampal neurogenesis via brain-derived neurotrophic factor and cyclin D1 regulation.2015
Author(s)
Kitamura, Y., Hattori, S., Yoneda, S., Watanabe, S., Kanemoto, E., Sugimoto, M., Kawai, T., Machida, A., Kanazaki, H., Miyazaki, I., Asanuma, M. and Sendo, T.
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Journal Title
Behav. Brain Res.
Volume: 292
Pages: 184-193
DOI
Related Report
Peer Reviewed
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[Journal Article] Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice2014
Author(s)
Tachibana H, Ogawa D, Sogawa N, Asanuma M, Miyazaki I, Terami N, Hatanaka T, Horigushi CS, Nakatsuka A, Eguchi J, Wada J, Yamada H, Takei K, Makino H
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Journal Title
Am J Physiol Renal Physiol
Volume: 306
Issue: 1
Pages: 105-115
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of Bupropion and Pramipexole on Cell Proliferation in the Hippocampus of Adrenocorticotropic Hormone-Treated Rats2014
Author(s)
Onoue, Y., Kuwatsuka, K., Miyazaki, I., Asanuma, M., Kitamura, Y. and Sendo, T.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 37
Issue: 2
Pages: 327-330
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access
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[Journal Article] Lack of dopaminergic inputs elongates the primary cilia of striatal neurons.2014
Author(s)
2.Miyoshi K, Kasahara K, Murakami S, Takeshima M, Kumamoto N, Sato A, Miyazaki I, Matsuzaki S, Sasaoka T, Katayama T, Asanuma M.
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Journal Title
PLoS One
Volume: 9(5)
Issue: 5
Pages: e97918-e97918
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Methylphenidate improves learning impairments and hyperthermia-induced seizures caused by an Scn1a mutation.2014
Author(s)
Ohmori, I., Kawakami, N., Liu, S., Wang, H., Miyazaki, I., Asanuma, M., Michiue, H., Matsui, H., Mashimo, T. and Ouchida, M.
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Journal Title
Epilepsia
Volume: 55
Issue: 10
Pages: 1558-1567
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] The Mechanisms of Electroconvulsive Stimuli in BrdU-Positive Cells of the Dentate Gyrus in ACTH-Treated Rats2013
Author(s)
Kuwatsuka, K., Hayashi, H., Onoue, Y., Miyazaki, I., Koyama, T., Asanuma, M., Kitamura, Y. and Sendo, T.
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Journal Title
Journal of Pharmacological Sciences
Volume: 122
Issue: 1
Pages: 34-41
DOI
NAID
ISSN
1347-8613, 1347-8648
Related Report
Peer Reviewed
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[Journal Article] Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models.2013
Author(s)
Asanuma, M., Miyazaki, I., Diaz-Corrales, F.J., Higashi, Y., Namba, M. and Ogawa, N.
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Journal Title
PLoS ONE
Volume: 8
Issue: 6
Pages: e65983-e65983
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Targeting 5-HT1A receptors in astrocytes to protect dopaminergic neurons in parkinsonian models.2013
Author(s)
Miyazaki, I., Asanuma, M., Murakami, S., Takeshima, M., Torigoe, N., Kitamura, Y. and Miyoshi, K.
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Journal Title
Neurobiol. Dis.
Volume: 59
Pages: 244-256
DOI
Related Report
Peer Reviewed
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[Presentation] Doxorubicin and cyclophosphamide treatment causes anxiety-like behavior and spatial cognition impairment in rats.2015
Author(s)
Kitamura, Y., Watanabe, S., Yoneda, S., Sugimoto, M., Kanemoto,b E., Kanzaki, H., Machida, A., Miyazaki, I., Asanuma, M., Sendo, T.
Organizer
45th Annual Meeting of Society for Neuroscience (Neuroscience 2015)
Place of Presentation
Chicago (USA)
Year and Date
2015-10-17
Related Report
Int'l Joint Research
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[Presentation] Effects of nicotine on doxorubicin and cyclophosphamide-induced spatial cognition and anxiety in rats.2015
Author(s)
Sugimoto, M., Kanemoto, E., Watanabe, S., Miyazaki, I., Asanuma, M., Kitamura, Y., Sendo, T.
Organizer
45th Annual Meeting of Society for Neuroscience (Neuroscience 2015)
Place of Presentation
Chicago (USA)
Year and Date
2015-10-17
Related Report
Int'l Joint Research
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[Presentation] Involvement of BDNF in doxorubicin and cyclophosphamide-induced spatial cognition in rats.2014
Author(s)
Kitamura, Y., Yoneda, S., Miyazaki, I., Asanuma, M., Sendo, T.
Organizer
44th Annual Meeting of Society for Neuroscience (Neuroscience 2014)
Place of Presentation
Washington, D,C.
Year and Date
2014-11-15 – 2014-11-19
Related Report
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[Presentation] Involvement of the 5-HT1A receptor function in the 8-OH-DPAT treatment on neurogenesis in ACTH-treated rats.
Author(s)
Kitamura, Y., Miyake, A., Hattori, S., Koyama, T., Miyazaki, I., Asanuma M. and Sendo, T.
Organizer
43rd Annual Meeting of Society for Neuroscience (Neuroscience2013)
Place of Presentation
San Diego
Related Report
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[Presentation] Ketamine exerts antidepressant-like effects during the forced swim test in adrenocorticotropic hormone-treated rats.
Author(s)
Nakamura, H., Yoneda, S., Miyake, A., Koyama, T., Miyazaki, I., Asanuma, M., Kitamura, Y. and Sendo, T.
Organizer
43rd Annual Meeting of Society for Neuroscience (Neuroscience2013)
Place of Presentation
San Diego
Related Report
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[Presentation] Comparative study of psychological response on treatment with doxorubicin and cyclophosphamide between rats and mice.
Author(s)
Yoneda, S., Hattori, S., Nakamura, H., Watanabe, S., Koyama, T., Miyazaki, I., Asanuma, M., Kitamura, Y. and Sendo, T.
Organizer
43rd Annual Meeting of Society for Neuroscience (Neuroscience2013)
Place of Presentation
San Diego
Related Report
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