Studies of rotenone-induced dopaminergic neurodegeneration focusing on brain region-specific astrocyte dysfunction.
Project/Area Number |
16K09673
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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) |
浅沼 幹人 岡山大学, 医歯薬学総合研究科, 教授 (00273970)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | パーキンソン病 / ロテノン / アストロサイト / ドパミン神経障害 / 腸管神経障害 / メタロチオネイン / ドパミン神経 / 腸管筋間神経叢 / ドパミンキノン / 腸管神経細胞 / グリア細胞 / ドパミン神経細胞 / ドパミン / 神経科学 / 脳神経疾患 / 脳・神経 / 薬理学 / アストログリア |
Outline of Final Research Achievements |
In this study, we revealed that astrocyte-conditioned media from low-dose rotenone-treated mesencephalic, but not striatal, astrocytes produced dopaminergic neuron-specific neurotoxicity, and that endogenous dopamine and its oxidation play an important role in mesencephalic astrocyte-mediated dopaminergic neurodegeneration. In addition, we demonstrated that reduction of antioxidative molecule metallothionein (MT) in enteric glial cells after rotenone-exposure induced enteric neurotoxicity. Oral administration of coffee components, caffeic acid and chlorogenic acid, upregulated MT expression both in the striatal astrocytes and enteric glial cells, and inhibited degeneration of central dopaminergic and peripheral enteric neurons in rotenone-treated mice. These results suggest possible involvement of brain region-specific glial dysfunction in neurotoxicity induced by environmental toxin rotenone.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は,孤発性パーキンソン病における重要な課題である「なぜ特定の神経系のみが障害されるのか?」を解明するため,アストロサイトの部位特異性に着目し,環境毒による神経障害における神経-グリア連関を検討したものである.本研究により,部位特異的なアストロサイト(様細胞)の機能不全が神経脆弱性を規定しうることを明らかにした.また,アストロサイト(様細胞)の発現因子を修飾させることで神経変性を阻止するというパーキンソン病に対する全く新しい観点からの治療法開発の基礎データを得ることができた.
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] Identification of transcription factors activated by methylmercury in mouse brain2017
Author(s)
Kim, M.S., Takahashi, T., Lee, J.Y., Miura, N., Asanuma, M., Hwang, G.W. and Naganuma, A.
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Journal Title
Fundamental Toxicological Sciences
Volume: 4
Issue: 1
Pages: 37-39
DOI
NAID
ISSN
2189-115X
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Changes in Metallothionein Isoform Expression in the Bones of Ovariectomized Rats2016
Author(s)
Chiharu Sogawa, Mika Ikegame, Ikuko Miyazaki, Toshiaki Ara, Yasuhiro Imamura, Yuka Okusha, Kazumi Ohyama, Masato Asanuma, Norio Sogawa, Toshio Yamamoto, Ken-ichi Kozaki
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Journal Title
Journal of Hard Tissue Biology
Volume: 25
Issue: 1
Pages: 21-26
DOI
NAID
ISSN
1341-7649, 1880-828X
Related Report
Peer Reviewed / Open Access
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[Journal Article] In vivo quantitative determination of the concentration of the polymerization agent methyl 2-benzoylbenzoate in intravenous injection solution and the cytotoxic effects of the chemical on normal human peripheral blood mononuclear cells.2016
Author(s)
Tsuboi, C., Kawasaki, Y., Yoshitome, K., Yagi, K., Miura, T., Esumi, S., Miyazaki, I., Asanuma, M., Kiyamura, Y. and Sendo, T.
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Journal Title
Environ. Sci. Pollut. Res. Int.
Volume: 23
Issue: 10
Pages: 10262-10269
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serotonin-1A agonist 8-OH-DPAT alleviates motor dysfunction and motor neuron degeneration in a model of amyotrophic lateral sclerosis.2016
Author(s)
Miyazaki, I., Murakami, S., Nakano, T., Torigoe, N., Kikuoka, R., Kitamura, Y., Sendo, T and Asanuma, M.
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Journal Title
Ann. Pharmacol. Pharmaceut.
Volume: 1
Pages: 1003-1003
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Involvement of enhanced 5-HT2A receptor function on doxorubicin and cyclophosphamide-induced anxiety-like behavior in rats.2018
Author(s)
Naito, N., Kitamura, Y., Nakamura, Y., Sumiyoshi, Y., Kan, S., Miyazaki, I., Asanuma, M. and Sendo, T.
Organizer
31st The International College of Neuropsychopharmacology (CINP World Congress)
Related Report
Int'l Joint Research
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[Presentation] Influence of benzodiazepine medications and GABAA receptor function on the pentobarbital-induced sleep behavior of lipopolysaccharide-treated mice.2018
Author(s)
Kitamura, Y., Okada, A., Hongo, S., Otsuki, K., Miki, A., Miyazaki, I., Asanuma, M. and Sendo, T.
Organizer
31st The International College of Neuropsychopharmacology (CINP World Congress)
Related Report
Int'l Joint Research
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[Presentation] Rotigotine protects dopaminergic neurons by targeting serotonin 1A receptors on astrocytes.2018
Author(s)
Asanuma, M., Miyazaki, I., Isooka, N., Kikuoka, R., Wada, K., Nakayama, E., Shin, K., Yamamoto, D., and Kitamura, Y.
Organizer
22nd International Congress of Parkinson’s Disease and Movement Disorders
Related Report
Int'l Joint Research
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[Presentation] Neuroprotective effects of coffee ingredients against rotenone induced neurodegeneration in parkinsonian model.2018
Author(s)
Miyazaki, I., Isooka, N., Kikuoka, R., Wada, K., Kitamura, Y. and Asanuma, M.
Organizer
22nd International Congress of Parkinson’s Disease and Movement Disorders
Related Report
Int'l Joint Research
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[Presentation] Possible involvement of metallothionein in rotenone-induced dopaminergic neurotoxicity.2018
Author(s)
Miyazaki, I., Kikuoka, R., Isooka, N., Murakami, S., Kitamura, Y., Asanuma, M.
Organizer
第59回日本神経学会学術大会
Related Report
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[Presentation] 妊娠・授乳期エポキシ樹脂暴露産仔マウス脳への影響に関する組織学的・行動学的検討.2018
Author(s)
浅沼幹人, 宮崎育子, 禅正和真, 菊岡 亮, 磯岡奈未, 新居 麗, 園部奏生, 船越英丸, 中山恵利香, 進 浩太郎, 山本大地, Kyle Quin
Organizer
日本解剖学会第73回中国・四国支部学術集会
Related Report
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[Presentation] Neuroprotective effects of rotigotine in parkinsonian mice.2017
Author(s)
Isooka, N., Miyazaki, I., Kikuoka, R., Wada, K., Nakayama, E., Yamamoto, D., Shin, K., Kitamura, Y. and Asanuma, M.
Organizer
第90回日本薬理学会年会
Place of Presentation
長崎
Year and Date
2017-03-15
Related Report
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[Presentation] Rotenone-induced dopaminergic neurotoxicity mediated by astrocytes.2017
Author(s)
Miyazaki, I., Murakami, S., Kikuoka, R., Isooka, N., Kitamura, Y. and Asanuma, M.
Organizer
第90回日本薬理学会年会
Place of Presentation
長崎
Year and Date
2017-03-15
Related Report
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[Presentation] Neuroprotective effects of antidepressant mirtazapine against dopaminergic neurodegeneration in cultured cells and in parkinsonian mice possibly by targeting astrocytes.2017
Author(s)
Asanuma, M., Miyazaki, I., Kikuoka, R., Murakami, S., Isooka, N. and Kitamura, Y.
Organizer
21st International Congress of Parkinson’s Disease and Movement Disorders
Related Report
Int'l Joint Research
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[Presentation] Rotenone induces astrocyte-mediated non-cell autonomous dopaminergic neurotoxicity.2017
Author(s)
Miyazaki, I., Murakami, S., Kikuoka, R., Isooka, N., Kitamura, Y. and Asanuma, M.
Organizer
21st International Congress of Parkinson’s Disease and Movement Disorders
Related Report
Int'l Joint Research
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[Presentation] Neuroprotective effects of rotigotine against dopaminergic neurodegeneration by targeting astrocytes.2017
Author(s)
Asanuma, M., Miyazaki, I., Isooka, N., Kikuoka, R., Wada, K., Nakayama, E., Shin, K., Yamamoto, D., and Kitamura, Y.
Organizer
23rd World Congress of Neurology
Related Report
Int'l Joint Research
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[Presentation] Rotenone-induced dopaminergic neurotoxicity promoted by mesencephalic astrocyte dysfunction2017
Author(s)
Miyazaki, I., Murakami, S., Kikuoka, R., Isooka, N., Kitamura, Y. and Asanuma, M.
Organizer
23rd World Congress of Neurology
Related Report
Int'l Joint Research
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[Presentation] Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection.2017
Author(s)
Kikuoka, R., Miyazaki, I., Kubota, N., Maeda, M., Kagawa, D., Moriyama, M., Kume, A., Murakami, S., Kitamura, Y. and Asanuma, M.
Organizer
47th Annual Meeting of Society for Neuroscience (Neuroscience 2017)
Related Report
Int'l Joint Research
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[Presentation] パーキンソン病モデルマウスにおけるミルタザピンの神経保護効果.2016
Author(s)
菊岡亮, 宮崎育子, 久保田菜月, 前田恵実, 香川大樹, 守山雅晃, 粂 明日香, 村上真樹, 北村佳久, 浅沼幹人, 千堂年昭
Organizer
第27回霧島神経薬理フォーラム
Place of Presentation
志賀島
Year and Date
2016-08-18
Related Report
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[Presentation] Mirtazapine protects dopaminergic neurons via astrocytes.2016
Author(s)
Miyazaki, I., Kikuoka, R., Kubota, N., Maeda, M., Kagawa, D., Moriyama, M., Kume, A., Murakami, S., Kitamura, Y., Asanuma, M.
Organizer
第57回日本神経学会学術大会
Place of Presentation
神戸
Year and Date
2016-05-21
Related Report
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[Book] 脳内環境辞典2017
Author(s)
浅沼幹人,宮崎育子
Total Pages
156
Publisher
メディカルドウ
ISBN
9784944157648
Related Report
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