Regulation, maintenance, and plasticity of central dopaminergic synapses

• Project/Area Number: 21700347
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: TOKUOKA Hirofumi 東京工業大学, 大学院・生命理工学研究科, 助教 (10452020)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ドーパミン / 黒質 / 線条体 / 大脳基底核 / チロシン水酸化酵素 / 遺伝子ノックアウトマウス / ノックアウトマウス / アデノ随伴ウイルス / アデノ随伴ウィルス

Research Abstract

The tyrosine hydroxylase(TH) gene, essential for dopamine synthesis, is partially ablated in adult nigrostriatal projection. TH reduction in axon terminals is slower than in soma, and dopamine is better maintained than TH. Our data suggest striatal dopamine is compensatorily regulated by axonal TH level and L-DOPA synthesis activity per TH level. This regulation has potential relevance to pathogenesis of Parkinson disease and other dopamine-related psychiatric disorders.

Research Products

• [Journal Article] Compensatory regulation of dopamine after ablation of the tyrosine hydroxylase gene in the nigrostriatal projection. J Biol Chem (2011)
  • Author(s): Tokuoka H, Muramatsu S, Sumi-Ichinose C, Sakane H, Kojima M, Aso Y, Nomura T, Metzger D, Ichinose H
  • Journal Title: published on-line
  • Peer Reviewed
• [Journal Article] Biopterin levels in the cerebrospinal fluid of patients with PARK8(I2020T) (2011)
  • Author(s): Koshiba S, Tokuoka H, Yokoyama T, Horiuchi E, Ichinose H, Hasegawa K
  • Journal Title: J Neural Transm Volume: 118 Pages: 899-903
  • Peer Reviewed
• [Journal Article] Partial biopterin deficiency disturbs postnatal development of the dopaminergic system in the brain (2011)
  • Author(s): Homma D, Sumi-Ichinose C, Tokuoka H, Ikemoto K, Nomura T, Kondo K, Katoh S, Ichinose H
  • Journal Title: J Biol Chem Volume: 286 Pages: 1445-1452
  • Peer Reviewed
• [Journal Article] Compensatory regulation of dopamine after ablation of the tyrosine hydroxylase gene in the nigrostriatal projection (2011)
  • Author(s): Tokuoka, H., Muramatsu, S., Sumi- Ichinose, C., Sakane, H., Kojima, M., Aso, Y., Nomura, T., Metzger, D., and Ichinose, H.
  • Journal Title: Journal of Biological Chemistry Volume: 286 Issue: 50 Pages: 43549-43558
  • DOI: 10.1074/jbc.m111.284729
  • Peer Reviewed
• [Journal Article] Partial biopterin deficiency disturbs postnatal development of the dopa minergic system in the brain. J Biol Chem 286:1445-1452 (2011)
  • Author(s): Homma D, Sumi-Ichinose C, Tokuoka H, Ikemoto K, Nomura T, Kondo K, Katoh S, Ichinose H
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 1445-1452
  • Peer Reviewed
• [Journal Article] Biopterin levels in the cerebrospinal fluid of patients with PARK8 (I2020T) (2011)
  • Author(s): Koshiba S, Tokuoka H, Yokoyama T, Horiuchi E, Ichinose H, Hasegawa K
  • Journal Title: Journal of Neural Transmission Volume: (In press)
  • Peer Reviewed
• [Journal Article] 疾患患者の脳脊髄液における還元型プテリジンレベルの測定:臨床試料中の還元型プテリジン測定へのポストカラム酸化法の応用 (2011)
  • Author(s): 小柴梢子、徳岡宏文、横山照夫、堀内恵美子、長谷川一子、一瀬宏
  • Journal Title: ビタミン Volume: 85 Pages: 63-69
  • Peer Reviewed
• [Journal Article] Accumulation of phosphorylated tyrosine hydroxylase into insoluble protein aggregates by inhibition of an ubiquitin-proteasome system in PC12D cells (2009)
  • Author(s): Kawahata I, Tokuoka H, Parvez H, Ichinose H
  • Journal Title: J Neural Transm Volume: 116 Pages: 1171-1578
  • Peer Reviewed
• [Journal Article] Accumulation of phosphorylated tyrosine hydroxylase into insoluble protein aggregates by inhibition of an ubiquitin-proteasome system in PC12D cells (2009)
  • Author(s): Kawahata I, Tokuoka H, Parvez H, Ichinose H
  • Journal Title: J Neural Transm 116 Pages: 1571-1578
  • Peer Reviewed
• [Presentation] 線条体におけるドーパミン生合成調節機構について (2012)
  • Author(s): 徳岡宏文
  • Organizer: 厚生労働科学研究費補助金難治性疾患克服研究事業3班合同公開シンポジウム
  • Place of Presentation: 帝京大学
  • Year and Date: 2012-02-19
• [Presentation] 初代培養海馬ニューロンへの蛍光標識カルモジュリンの導入とライブイメージング (2011)
  • Author(s): 門脇広樹、徳岡宏文、細谷悟史、大野敏、横川隆志、西川一八、林宣宏、一瀬宏
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-24
• [Presentation] 成熟脳におけるNurr1、Nur77の機能解析に用いる遺伝子改変マウスの作成 (2011)
  • Author(s): 畑中貴之、畑中康人、伊藤岳人、五十嵐孝幸、徳岡宏文、村松真一、遠藤毅、廣崎賢、高崎昭彦、林宣宏、Daniel Metzger、一瀬宏
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-09-16
• [Presentation] 黒質線条体ドーパミン投射における経軸索的ドーパミン量の代償 (2011)
  • Author(s): 徳岡宏文、村松慎一、鷲見-一瀬千穂、Daniel Metzger、一瀬宏
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-09-15
• [Presentation] 黒質-線条体ドーパミン投射系におけるドーパミン量の制御機構 (2010)
  • Author(s): 徳岡宏文、村松慎一、一瀬宏
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-09-02
• [Presentation] 黒質-線条体ドーパミン投射系におけるドーパミン量の制御機構 (2010)
  • Author(s): 徳岡宏文、村松慎一、一瀬宏
  • Organizer: 第33回 日本神経科学大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-09-02
• [Presentation] 黒質-線条体投射におけるドーパミン量制御機構 (2010)
  • Author(s): 徳岡宏文、一瀬宏
  • Organizer: 包括脳ワークショップ
  • Place of Presentation: ホテルさっぽろ芸文館
  • Year and Date: 2010-07-29
• [Presentation] 中枢神経黒質-線条体系ドーパミン投射の恒常性維持-チロシン水酸化酵素とドーパミン量の代償的制御 (2009)
  • Author(s): 徳岡宏文、一瀬宏
  • Organizer: 日本神経科学学会2009年年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-09-16
• [Presentation] 中枢神経黒質-線条体系ドーパミン投射の恒常性維持-チロシン水酸化酵素とドーパミン量の代償的制御 (2009)
  • Author(s): Tokuoka H, Ichinose H
  • Organizer: 日本神経科学学会 2009年年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-09-16
• [Presentation] Regulation of tyrosine hydroxylase protein level and DA content in nigrostriatal dopaminergic projection (2009)
  • Author(s): Tokuoka H, Ichinose H
  • Organizer: Gordon Research Conference 2009, Catechol Amine
  • Place of Presentation: University of New England, ME, USA
• [Remarks]
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• [Remarks]
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• [Remarks]
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