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著作: Kato Hiroyuki/[荒木 勉]/Imai Yutaka/Takahashi Akira/Itoyama Yasuto/Ptotection of dopamininergic neurons with a novel astrocyte modulating agent (R)-(-)2-propyloctanoic acid (ONO-2506) in an MPTP-treated mouse model of Parkinson's disease/[Journal of the Neurological Sciences]

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89076
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690163
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2013年6月10日(月) 11:56:38
Operator
三木 ちひろ
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[学科長]/[徳島大学.薬学部.薬学科]
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨 Peer Review
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Kato Hiroyuki
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 荒木 勉
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Imai Yutaka
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Takahashi Akira
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Itoyama Yasuto
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Ptotection of dopamininergic neurons with a novel astrocyte modulating agent (R)-(-)2-propyloctanoic acid (ONO-2506) in an MPTP-treated mouse model of Parkinson's disease

副題 任意
要約 任意

(英) We examined the neuroprotective effects of a novel astrocyte-modulating agent, (R)-(-)-2-propyloctanoic acid (ONO-2506), in a mouse model of Parkinson's disease. Male C57BL/6 mice received four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (10 mg/kg) at 1-h intervals. Dopamine content in the striatum, measured with HPLC 3 days after MPTP injection, was reduced to 23% of control. But this dopamine depletion was dose-dependently prevented by repeated treatments with ONO-2506 (3, 10 and 30 mg/kg, i.p.) administered 1, 6, 24 and 48 h after MPTP injection (51% of control in 30 mg/kg group, p<0.01). ONO-2506 treatment (30 mg/kg) started after 6 h, followed by treatments at 24 and 48 h, also prevented the reduction of dopamine content (42% of control vs. 11% of control in the saline-treated group, p<0.01). We also performed immunohistochemistry for tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). The MPTP injection resulted in a loss of TH-positive dopaminergic neurons (42% of control, p<0.01) in the substantia nigra after 7 days, but ONO-2506 treatment prevented this neuronal loss (70% of control, p<0.01). The MPTP injection led to reactive astrocytosis in the striatum after 7 days, but ONO-2506 induced earlier, moderate astrocytic activation after 3-7 days. These findings show that ONO-2506 protects dopaminergic neurons against MPTP neurotoxicity probably through facilitating astrocytic support for neuronal recovery from injury. Pharmacological modulation of astrocytes may offer a novel therapeutic strategy for Parkinson's disease.

キーワード 推奨
  1. (英) 3,4-Dihydroxyphenylacetic Acid
  2. (英) Animals
  3. (英) Astrocytes
  4. (英) Corpus Striatum
  5. (英) Disease Models, Animal
  6. ドーパミン(dopamine)
  7. (英) Dose-Response Relationship, Drug
  8. (英) Drug Interactions
  9. (英) Glial Fibrillary Acidic Protein
  10. 免疫組織化学(immunohistochemistry)
  11. (英) Male
  12. (英) Mice
  13. (英) Mice, Inbred C57BL
  14. (英) Neuroprotective Agents
  15. (英) Octanoic Acids
  16. パーキンソン病(Parkinson's disease)
  17. (英) Parkinsonian Disorders
  18. (英) Substantia Nigra
  19. (英) Time Factors
  20. (英) Tyrosine 3-Monooxygenase
発行所 推奨
誌名 必須 Journal of the Neurological Sciences(World Federation of Neurology)
(pISSN: 0022-510X, eISSN: 1878-5883)
ISSN 任意 0022-510X
ISSN: 0022-510X (pISSN: 0022-510X, eISSN: 1878-5883)
Title: Journal of the neurological sciences
Title(ISO): J Neurol Sci
Publisher: Elsevier BV
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 208
必須 1-2
必須 9 15
都市 任意
年月日 必須 2003年 4月 15日
URL 任意
DOI 任意 10.1016/S0022-510X(02)00411-2    (→Scopusで検索)
PMID 任意 12639719    (→Scopusで検索)
NAID 任意
WOS 任意
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku,Sendai 980-8574, Japan. katoh@mail.cc.tohoku.ac.jp

  2. (英) Article.PublicationTypeList.PublicationType: Comparative Study

  3. (英) Article.PublicationTypeList.PublicationType: Journal Article

  4. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't