Reorganization of basal ganglia circuitry in animal model of parkinson's disease by stimulation of subthalamic nucleus

• Project/Area Number: 22659264
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Kitasato University
• Principal Investigator: SAJI Makoto 北里大学, 医療衛生学部, 教授 (50114179)
• Co-Investigator(Kenkyū-buntansha): TAKIYAMA Youko 北里大学, 医学部, 講師 (60265593) ; SATO Sumito 北里大学, 医学部, 助教 (40266052)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,170,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 片側パーキンソン病モデル / 深部脳刺激 / 視床下核 / 運動症状改善 / NMDA受容体NR2Bアンタゴニスト / 基底核回路 / 片側パーキンソン病モデ / 深部脳刺激(DBS) / 視床下核(STN) / 運動症状改善効果 / バーキンソン病モデル / 運動症状改善後効果 / NMDA-R依存LTP誘導強化 / NMDA-RサブユニットNR2Bアンタゴニスト

Research Abstract

To test the hypothesis that STN-DBS inducesa long-lasting reconstruction of basal gangliacircuitry in parkinsonian rats mediatedby expression of LTP on synapses in the nearby nuclei, we examined whether NMDA receptor(NMDAR) subunit NR2B antagonist potentiates the alleviating after-effect of STN-DBS and lasts the improvement of motor deficits by transient STN-DBS long for hours or days.
Prior to the test for the potentiation of alleviating effect of STN-DBS by NR2B antagonist in hemi-parkinsonian rats, we first examined whether mono-therapeutic treatment with NR2B antagonist(ifenprodil) improves the motor symptoms in hemi-parkinsonian rats. As a result, in hemiparkinsonianrats, we found that ifenprodil did not cause an improvement of the deficits of motor coordination, while the drug potentiated the ameliorative effect of L-DOPAon the deficit of motor coordination whencombined with L-DOPA, suggesting the synergistic action of ifenprodil on the antiparkinsonian effect of L-DOPA. From this result, it is suggested that a combined treatment with STN-DBS and NR2B antagonist could be more effective than STN-DBS alone to improve the chronic L-DOPA-induced dyskinesias with less side-effect.

Research Products

• [Journal Article] Evaluation of neurotoxicity of artificial dura mater and dura mater containing a high concentration of dibutyltin in rats after intracranial implantation (2012)
  • Author(s): Tsunoda M, Ikeuchi R, Tsuji M, Inoue Y, Ito K, Katagiri H, Akita H, Saji M., Yuba T, Yamada T, Tsuchiya T, Aizawa Y
  • Journal Title: Kitasato Med J Volume: 42 Pages: 67-75
  • Peer Reviewed
• [Journal Article] Activation of the NMDA receptor involved in the alleviating after-effect of repeated stimulation of the subthalamic nucleus on motor deficits in hemiparkinsonia rats (2010)
  • Author(s): Akita H, Honda Y, Ogata M, Noda K, Saji M
  • Journal Title: Brain Res Volume: 1306 Pages: 159-167
  • Peer Reviewed
• [Journal Article] Enhanced inhibitory effects of TBT chloride on the development of F_1 rats (2010)
  • Author(s): Asakawa H, Tsunoda M, Kaido T, Hosokawa M, Sugaya C, Inouue Y, Kudo Y, Satoh T, Katagiri H, Akita H, Saji M, Wakasa M, Negish T, Tashiro T, Aizawa Y
  • Journal Title: Arch Environ ContamTaxicol Volume: 58 Pages: 1065-1073
  • Peer Reviewed
• [Presentation] Switching from learning behavior to thigmotaxis in mater maze induced by in vivo delivery of antibody against AMPA receptor GluA1-C terminus via HVJ-E vector into hippocampal neurons in rats (2011)
  • Author(s): Saji M, Shimizu D, Ogata M, Noda K, Suzuki N, Akita H
  • Organizer: 41st annual meeting of society for neuroscience
  • Place of Presentation: Washington DC
  • Year and Date: 2011-11-15
• [Presentation] Loss of motivation for learning in water maze by in vivo delivery of antibody to AMPA receptor GluR1-C terminus via HVJ-E vector into hippocampal CA1 neurons in rats (2011)
  • Author(s): Saji M, Ogata M, Noda K, Suzuki N, Akita H
  • Organizer: IBRO world congress of neuroscience
  • Place of Presentation: Firenze, Italy
  • Year and Date: 2011-07-12
• [Presentation] The neurotoxic effects of tributylin on mele F1 rats by continuous exposurefrom the fetal stage through their developing stages (2011)
  • Author(s): Ikeuchi R, Kido T, Sugaya C, Tsunoda M, Katagiri H, Uchimura A, Akita H, Saji M, Aizawa Y
  • Organizer: 50th annual meeting for societyof toxicology
  • Place of Presentation: Washington DC
• [Presentation] NMDA receotpr-mediated plasticity in the alleviating after-effect of subthalamic stimulation on akinetic motor deficit in rat models of Parkinson's disease (2010)
  • Author(s): Akita H, Honda Y, Ogata, Noda K, Saji M
  • Organizer: 40th annual meeting of society for neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2010-11-15
• [Presentation] NMDAR-mediated synaptic plasticity involved in the alleviating after-effect of STN-DBS on akinetic motor deficits in Parkinson's model rats. (2010)
  • Author(s): Akita H, Honda Y, Ogata M, Ogura T, Saji M
  • Organizer: Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-15
• [Presentation] Paclitaxel-induced hyperalgesia modulates NR1 receptor expression in the frontal cortex and negative affective component of pain in rats (2010)
  • Author(s): Noda K, Akita H, Ogata M, Saji M
  • Organizer: 13th world congress on pain
  • Place of Presentation: Montreal
  • Year and Date: 2010-08-30
• [Presentation] Evaluation of TBT neurotoxicity in developing male F1 rats by open field tests (2010)
  • Author(s): Tsunoda M, Kado T, Ikeuchi R, Hosokawa M, Sugaya C, Inoue Y, Kudo Y, Akita H, Saji M, Takeuchi Y, Yoshioka R, Tashiro T, Aizawa Y
  • Organizer: 49th Annual Meeting for Society of Toxicology
  • Place of Presentation: Salt Lake City
  • Year and Date: 2010-03-01