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Neuropharmacological study on transcription modulating factors activated by repeated administration of L-DOPA in the rat brain

Research Project

Project/Area Number 19591364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionUniversity of Miyazaki

Principal Investigator

ISHIDA Yasushi  University of Miyazaki, 医学部・臨床神経科学講座精神医学分野, 教授 (20212897)

Co-Investigator(Kenkyū-buntansha) TAKEDA Ryuichiro  宮崎大学, 医学部・臨床神経科学講座精神医学分野, 助教 (90336298)
NISHIMORI Toshikazu  宮崎大学, 医学部・臨床神経科学講座精神医学分野, 教授 (20112211)
UEDA Yuto  宮崎大学, 医学部・臨床神経科学講座精神医学分野, 准教授 (70244192)
EBIHARA Kosuke  宮崎大学, 医学部・臨床神経科学講座精神医学分野, 医員 (20510720)
NONAKA Hiroi  宮崎大学, 医学部・臨床神経科学講座精神医学分野, 助教 (30311591)
MATSUO Hisae  宮崎大学, 医学部・臨床神経科学講座精神医学分野, 心理士 (70511476)
安部 博史  宮崎大学, 医学部, 助教 (20344848)
Co-Investigator(Renkei-kenkyūsha) ABE Hiroshi  九州ルーテル学院大学, 人文学部, 准教授 (20344848)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsL-DOPA / 転写調節因子 / パーキンソン病 / 神経科学
Research Abstract

本研究では, 抗パーキンソン病薬のL-DOPAを反復投与することによる2種類の転写調節因子蛋白(c-Fos及びZif268)の脳内発現様式の変化を, 免疫組織化学法を用いて, ヘミ・パーキンソン病モデルラットを対象に観察した。
1) 6-hydroxydopamineの脳内局所(左側の内側前脳束)投与によりヘミ・パーキンソン病モデルラットを作成し, 行動および形態学的変化を観察し, ヘミ・パーキンソン病モデルとしての妥当性を評価した。更に, モデルラットの破壊側線条体に, ラット胎仔中脳由来のドーパミン細胞を移植し, 移植後の行動(メタンフェタミン誘起回転運動の正常化)・形態学的変化(線条体移植部のドーパミン活性の回復)を経時的に観察した。2) メタンフェタミン腹腔内投与に, 当該モデルラットの大脳基底核(線条体・淡蒼球外節・黒質網様層)において, FosおよびZif268は異なる様式で発現した。3) 破壊側線条体への胎仔中脳細胞の移植により, メタンフェタミンによる線条体・淡蒼球外節におけるFos発現, 線条体におけるZif268発現は正常化した。しかし, 黒質網様層のFos発現および淡蒼球外節・黒質網様層のZif268発現に変化はみられなかった。4) L-DOPA単回投与(腹腔内)により, モデルラット破壊側線条体その他のドーパミン神経投射部位で, FosおよびZif268の過剰発現が認められた。この現象は, 胎仔中脳細胞移植により正常化された。L-DOPA繰り返し投与に伴い, 破壊反対側への回転運動及び不随意運動の亢進が認められた。現在, その病態について検討中である。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (50 results)

All 2009 2008 2007 Other

All Journal Article (23 results) (of which Peer Reviewed: 23 results) Presentation (25 results) Remarks (2 results)

  • [Journal Article] Effects of intrathecal administration of newer antidepressants on mechanical allodynia in rat models of neuropathic pain2009

    • Author(s)
      Ikeda T, Ishida Y, Naono R, Takeda R, Abe H, Nakamura T, Nishimori T
    • Journal Title

      Neurosci Res 63

      Pages: 42-46

    • NAID

      10027499235

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional dissociation between rat perirhinal cortex and hippocampus in object and place discrimination tasks2009

    • Author(s)
      Abe H, Ishida Y, Nonaka H, Iwasaki T
    • Journal Title

      Behav Brain Res 197(2)

      Pages: 388-397

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Levetiracetam enhances endogenous antioxidant in the hippocampus of rats : in vivo evaluation by brain microdialysis combined with ESR spectroscopy2009

    • Author(s)
      Ueda Y, Doi T, Takaki M, Nagatomo K, Nakajima A, Willmore LJ
    • Journal Title

      Brain Res 1266

      Pages: 1-7

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional dissociation between rat perirhinal cortex and hippocampus in object and place discrimination tasks2009

    • Author(s)
      Abe H, et al.
    • Journal Title

      Behavioural Brain Research 197

      Pages: 388-397

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of intrathecal administration of newer antidepressants on mechanical allodynia in rat models of neuropathic pain2009

    • Author(s)
      Ikeda T, et al.
    • Journal Title

      Neurosci Res 63

      Pages: 42-46

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Psychological prenatal stress reduced the number of BrdU immunopositive cells in the dorsal hippocampus without affecting the open field behavior of male and female rats at one month of age2008

    • Author(s)
      Odagiri K, Abe H, Kawagoe C, Takeda R, Ikeda T, Matsuo H, Nonaka H, Ebihara K, Nishimori T, Ishizuka Y, Hashiguchi H, Ishida Y
    • Journal Title

      Neurosci Lett 446

      Pages: 25-29

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A community intervention trial of multimodal suicide prevention program in Japan : A Novel multimodal Community Intervention program to prevent suicide and suicide attempt in Japan, NOCOMIT-J2008

    • Author(s)
      Ono Y, Awata S, Iida H, Ishida Y, Ishizuka N, Iwasa H, Kamei Y, Motohashi Y, Nakagawa A, Nakamura J, Nishi N, Otsuka K, Oyama H, Sakai A, Sakai H, Suzuki Y, Tajima M, Tanaka E, Uda H, Yonemoto N, Yotsumoto T, Watanabe T
    • Journal Title

      BMJ Public Health 8

      Pages: 315-315

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential expression of Fos and Zif268 in the nigrostriatal system after methamphetamine administration in a rat model of Parkinson's disease2008

    • Author(s)
      Ishida Y, Kawai K, Magata Y, Ebihara K, Takeda R, Abe H, Yoshimoto M, Hashiguchi H, Odagiri K, Matsuo H, and Nishimori T
    • Journal Title

      Synapse 62(12)

      Pages: 920-926

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Different response between production of free radicals induced by central and peripheral administration of interleukin-1beta in conscious rats2008

    • Author(s)
      Ishizuka Y, Abe H, Nakane H, Kannan H, Ishida Y
    • Journal Title

      Neurosci Res 60(1)

      Pages: 10-14

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacological characterization of desensitization in scratching behavior induced by intrathecal administration of hemokinin-1 in the rat2008

    • Author(s)
      Naono R, Nakayama T, Ikeda T, Matsusima O, Nishimori T
    • Journal Title

      Neuropeptides 42

      Pages: 47-55

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential expression of Fos and Zif268 in the nigrostriatal system after methamphetamine administration in a rat model of Parkinson's disease2008

    • Author(s)
      Ishida Y, et al.
    • Journal Title

      Synapse 62

      Pages: 920-926

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Psychological prenatal stress reduced the number of BrdU immunopositive cells in the dorsal hippocampus without affecting the open field behavior of male and female rats at one month of age2008

    • Author(s)
      Odagiri K, et al.
    • Journal Title

      Neurosci Lett 446

      Pages: 25-29

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different response between production of free radicals induced by central and peripheral administration of interleukin-lbeta in conscious rats2008

    • Author(s)
      Ishizuka Y, et. al.
    • Journal Title

      Neuroscience Research 60

      Pages: 10-14

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis2007

    • Author(s)
      Abe H, Hidaka N, Kawagoe C, Odagiri K, Watanabe Y, Ikeda T, Ishizuka Y, Hashiguchi H, Takeda R, Nishimori T, Ishida, Y
    • Journal Title

      Neurosci Res 59(2)

      Pages: 145-151

    • NAID

      10024417223

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo activation of N-methyl-D-aspartate receptors generates free radicals and reduces antioxidant ability in the rat hippocampus : experimental protocol of in vivo ESR spectroscopy and microdialysis for redox status evaluation2007

    • Author(s)
      Ueda Y, Doi T, Nagatomo K, Nakajima A
    • Journal Title

      Brain Res 1178

      Pages: 20-27

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo EPR estimation of bilateral hippocampal antioxidant ability of rats with epileptogenesis induced by amygdalar FeCl3 microinjection2007

    • Author(s)
      Ueda Y, Yokoyama H, Nakajima A, Takaki M, Nagatomo K, Doi T, Willmore LJ
    • Journal Title

      Epilepsia 48

      Pages: 1947-1951

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional role for redox in the epileptogenesis : molecular regulation of glutamate in the hippocampus of FeCl3-induced limbic epilepsy model2007

    • Author(s)
      Ueda Y, Doi T, Nagatomo K, Willmore LJ, Nakajima A
    • Journal Title

      Exp Brain Res 181

      Pages: 571-577

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of levetiracetam on molecular regulation of hippocampal glutamate and GABA transporters in rats with chronic seizures induced by amygdalar FeCl3 injection2007

    • Author(s)
      Ueda Y, Doi T, Nagatomo K, Tokumaru J, Takaki M, Willmore LJ
    • Journal Title

      Brain Res 1151

      Pages: 55-61

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Leucine at the carboxyl-terminal of endokinins C and D contributes to elicitation of the antagonistic effect on substance P in rat pain processing2007

    • Author(s)
      Naono R, Nakayama T, Ikeda T, Matsushima O, Nishimori T
    • Journal Title

      Brain Res 1165

      Pages: 71-80

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The common carboxyl-terminal region of novel tachykinin peptides contributes to induce desensitization in scratching behavior of rats2007

    • Author(s)
      Naono R, Yoshioka D, Ikeda T, Nakayama T, Nishimori T
    • Journal Title

      Brain Res Bull 71

      Pages: 461-465

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis2007

    • Author(s)
      Abe H, et. al.
    • Journal Title

      Neuroscience Research 59

      Pages: 145-151

    • NAID

      10024417223

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analgesic effect of milnacipran is associated with c-Fos expression in the anterior cingulate cortex in the rat neuropathic pain model

    • Author(s)
      Takeda R, Watanabe Y, Ikeda T, Abe H, Ebihara K, Matsuo H, Nonaka H, Hashiguchi H, Nishimori T, Ishida Y
    • Journal Title

      Neurosci Res (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nystagmus using video-oculography in psychiatric patients

    • Author(s)
      Kiyomizu K, Matsuda K, Torihara K, Nakayama M, Komaki S, Tono T, Ishida Y, Yoshida K, Kimitsuki T
    • Journal Title

      Eur Arch Otorhinolaryngol (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] 90歳以上の超高齢者の精神医療について考える2009

    • Author(s)
      宇田川充隆, 吉牟田千賀, 井上輝彦, 三山吉夫, 石田康
    • Organizer
      第19回日本老年医学会九州地方会
    • Place of Presentation
      宮崎郡
    • Year and Date
      2009-03-07
    • Related Report
      2008 Final Research Report
  • [Presentation] 器質的異常の見出せない高齢者の身体愁訴に関する薬物療法の検討2009

    • Author(s)
      船橋英樹, 武田龍一郎, 松尾寿栄, 石田康, 荒木竜二, 尾薗和彦, 谷口浩, 安部博史, 三山吉夫
    • Organizer
      第19回日本老年医学会九州地方会
    • Place of Presentation
      宮崎郡
    • Year and Date
      2009-03-07
    • Related Report
      2008 Final Research Report
  • [Presentation] うつ状態が先行したレビー小体型認知症の2例2009

    • Author(s)
      吉野未来, 船橋英樹, 林要人, 石田康, 山下英一郎, 長町茂樹, 三山吉夫
    • Organizer
      第19回日本老年医学会九州地方会
    • Place of Presentation
      宮崎郡
    • Year and Date
      2009-03-07
    • Related Report
      2008 Final Research Report
  • [Presentation] 妊娠ラットに対する心理学的ストレスが出生後の仔ラットの行動発達に及ぼす影響について2009

    • Author(s)
      安部博史, 小田切啓, 石田康
    • Organizer
      第13回神経科学領域における分子モニタリングシンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2009-01-10
    • Related Report
      2008 Final Research Report
  • [Presentation] 新生仔期脳内アセチルコリン系損傷ラットにおけるムスカリン性受容体作動薬の効果2009

    • Author(s)
      野中博意, 安部博史, 蛯原功介, 松尾寿栄, 石田康
    • Organizer
      第13回神経科学領域における分子モニタリングシンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2009-01-10
    • Related Report
      2008 Final Research Report
  • [Presentation] ドーパミン神経研究と精神医学の接点2008

    • Author(s)
      石田康
    • Organizer
      守口市精神科学術フォーラム
    • Place of Presentation
      守口市
    • Year and Date
      2008-11-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 妄想を伴ったうつ病エピソードにフルボキサミンが著効した2例~SPECT所見を交えて~2008

    • Author(s)
      船橋英樹, 吉野未来, 石田康
    • Organizer
      第2回九州地区向精神薬セミナー学術講演会
    • Place of Presentation
      福岡市
    • Year and Date
      2008-11-12
    • Related Report
      2008 Final Research Report
  • [Presentation] 疼みの治療における抗うつ薬の役割2008

    • Author(s)
      石田康
    • Organizer
      熊本県精神科病院協会学術講演会
    • Place of Presentation
      熊本市
    • Year and Date
      2008-03-25
    • Related Report
      2008 Final Research Report
  • [Presentation] 陰性症状様の所見を認めた側頭葉てんかんの一例2008

    • Author(s)
      松本太志, 蛯原功介, 井上雅文, 松本亮, 石田康
    • Organizer
      第61回九州精神神経学会
    • Place of Presentation
      宮崎市
    • Related Report
      2008 Final Research Report
  • [Presentation] 初診時認知症を伴わない老年期幻覚・妄想状態の23例2008

    • Author(s)
      宇田川充隆, 吉牟田千賀, 井上輝彦, 三山吉夫, 石田康
    • Organizer
      第61回九州精神神経学会
    • Place of Presentation
      宮崎市
    • Related Report
      2008 Final Research Report
  • [Presentation] 2種の神経因性疼痛モデルラットにみられる熱アロディニアに対する抗うつ薬の効果2008

    • Author(s)
      池田哲也, 武田龍一郎, 石田康, 西森利數
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] 糖尿病性疼痛モデルラットへの熱刺激による疼痛行動に対する抗うつ薬, SNRI, SSRIの効果2008

    • Author(s)
      池田哲也, 武田龍一郎, 石田康, 西森利數
    • Organizer
      第37回日本慢性疼痛学会
    • Place of Presentation
      宇都宮市
    • Related Report
      2008 Final Research Report
  • [Presentation] 脳内自己刺激行動実験による脳内強化機構の解析2007

    • Author(s)
      石田康, 中原大一郎
    • Organizer
      第4回Neuroscience Frontier Research Conference
    • Place of Presentation
      木更津市
    • Related Report
      2008 Final Research Report
  • [Presentation] 多彩な精神症状と網膜色素変性症を呈したミトコンドリア脳筋症の姉妹例2007

    • Author(s)
      船橋英樹, 陣内紗織, 荒木竜二, 尾薗和彦, 谷口浩, 石田康, 三山吉夫
    • Organizer
      第60回九州精神神経学会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] Analgesic effect of milnacipran is associated with anterior cingulate cortex in the rat2007

    • Author(s)
      Takeda R, Ikeda T, Abe H, Ebihara K, Hashiguchi H, Nishimori T, Ishida Y
    • Organizer
      37th Annual Meeting Society for Neuroscience
    • Place of Presentation
      San Diego
    • Related Report
      2008 Final Research Report
  • [Presentation] The number of Fos-positive cells in the perirhinal cortex correlates negatively to the rate of correct responses but not to the number of trials in object discriminationtask in rats2007

    • Author(s)
      Abe H, Yukie M, Ishida Y
    • Organizer
      37th Annual Meeting Society for Neuroscience
    • Place of Presentation
      San Diego
    • Related Report
      2008 Final Research Report
  • [Presentation] Alteration of striatal [11C]raclopride and [18F]FDOPA uptake precedes development of methamphetamine-induced rotation in the unilateral 6-hydroxydopamine lesioned rats2007

    • Author(s)
      Ishida Y, Kawai K, Magata Y, Abe H, Takeda R, Ebihara K, Yoshimoto M, Mukai T, Saji H
    • Organizer
      37th Annual Meeting Society for Neuroscience
    • Place of Presentation
      San Diego
    • Related Report
      2008 Final Research Report
  • [Presentation] 皮質基底核変性症の一症例2007

    • Author(s)
      河野次郎, 鶴衛亜里沙, 倉山茂樹, 二宮嘉正, 石田康, 三山吉夫
    • Organizer
      第60回九州精神神経学会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] 認知症を伴う高齢者への身体的虐待の3症例2007

    • Author(s)
      宇田川充隆, 井上輝彦, 三山吉夫, 石田康
    • Organizer
      第60回九州精神神経学会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] 脳実質内漏出性出血による精神障害の一剖検例2007

    • Author(s)
      長友慶子, 笠新逸, 澤大介, 長野理恵, 鶴衛圭一, 石田康, 井上輝彦, 三山吉夫
    • Organizer
      第60回九州精神神経学会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] 躁状態を呈した神経梅毒の一例2007

    • Author(s)
      石田裕一郎, 山口志保子, 武田龍一郎, 石田康
    • Organizer
      第60回九州精神神経学会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] 両側シルビウス裂周囲に優位な多小脳回を有するてんかん焦点の局在性について2007

    • Author(s)
      津山陽子, 植田勇人, 松本太志, 石田康
    • Organizer
      第60回九州精神神経学会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] オレキシンは脳内自己刺激における報酬効果を抑制する2007

    • Author(s)
      畑敏道, Jihuan Chen, 高橋太郎, Shuibo Gao, 石田康, 伊達紫, 中原大一郎
    • Organizer
      第30回日本神経科学大会・第50回日本神経化学会大会・第17回日本神経回路学会大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] SSRI・SNRIの抗不安作用におけるバゾプレッシンV1b受容体の関与2007

    • Author(s)
      石塚雄太, 安部博史, 田上昭人, 河南洋, 石田康
    • Organizer
      第29回日本生物学的精神医学会・第37回日本神経精神薬理学会合同年会
    • Place of Presentation
      札幌市
    • Related Report
      2008 Final Research Report
  • [Presentation] Alteration of striatal [11C] raclopride and [18F] FDOPA uptake precedes development of methamphetamine-induced rotation in the unilateral 6-hydroxydopamine lesioned rats2007

    • Author(s)
      Ishida Y, et. al.
    • Organizer
      37th Annual Meeting Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.miyazaki-u.ac.jp/psychiatry/index.htm

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.med.miyazaki-u.ac.jp/psychiatry/index.htm

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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