| Project/Area Number |
22659264
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kitasato University |
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Principal Investigator |
SAJI Makoto 北里大学, 医療衛生学部, 教授 (50114179)
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| 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)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥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)
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| 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 |
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| 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.
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