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

通过刺激底丘脑核重组帕金森病动物模型中的基底神经节回路

• 批准号: 22659264
• 负责人: SAJI Makoto
• 金额: $ 2.03万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659264/
• 关键词: 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

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.

为了验证 STN-DBS 通过附近核突触上 LTP 表达介导的帕金森病大鼠基底神经节回路的持久重建这一假设，我们检查了 NMDA 受体 (NMDAR) 亚基 NR2B 拮抗剂是否能增强 STN-DBS 的后效缓解，并通过短暂的持续改善运动缺陷 STN-DBS 持续数小时或数天。在测试 NR2B 拮抗剂对半侧帕金森病大鼠的 STN-DBS 缓解效果的增强作用之前，我们首先检查了 NR2B 拮抗剂（艾芬地尔）单一治疗是否能改善半侧帕金森病大鼠的运动症状。结果，在偏侧帕金森病大鼠中，我们发现艾芬地尔不会改善运动协调缺陷，而该药物与左旋多巴合用时增强了左旋多巴对运动协调缺陷的改善作用，表明艾芬地尔对左旋多巴的抗帕金森病作用具有协同作用。由此结果表明，STN-DBS和NR2B拮抗剂联合治疗比单独使用STN-DBS更能有效改善慢性L-DOPA引起的运动障碍，且副作用较小。

项目成果

Evaluation of neurotoxicity of artificial dura mater and dura mater containing a high concentration of dibutyltin in rats after intracranial implantation

人工硬脑膜及含高浓度二丁基锡硬脑膜颅内植入后对大鼠的神经毒性评价

• 发表时间: 2012
• 期刊: Kitasato Med J
• 作者: Tsunoda M;Ikeuchi R;Tsuji M;Inoue Y;Ito K;Katagiri H;Akita H;Saji M.;Yuba T;Yamada T;Tsuchiya T;Aizawa Y
• 通讯作者: Aizawa Y

Evaluation of TBT neurotoxicity in developing male F1 rats by open field tests

旷场试验评价 TBT 对发育中的雄性 F1 大鼠的神经毒性

• 发表时间: 2010
• 作者: 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
• 通讯作者: Aizawa Y

The neurotoxic effects of tributylin on mele F1 rats by continuous exposurefrom the fetal stage through their developing stages

从胎儿期到发育阶段持续暴露三丁醇对混杂 F1 大鼠的神经毒性作用

• 发表时间: 2011
• 作者: Ikeuchi R;Kido T;Sugaya C;Tsunoda M;Katagiri H;Uchimura A;Akita H;Saji M;Aizawa Y
• 通讯作者: Aizawa Y

NMDAR-mediated synaptic plasticity involved in the alleviating after-effect of STN-DBS on akinetic motor deficits in Parkinson's model rats.

NMDAR 介导的突触可塑性参与缓解 STN-DBS 对帕金森病模型大鼠运动不能障碍的后遗症。

• 发表时间: 2010
• 作者: Akita H;Honda Y;Ogata M;Ogura T;Saji M
• 通讯作者: Saji M

Enhanced Inhibitory Effects of TBT Chloride on the Development of F1 Rats

• DOI: 10.1007/s00244-009-9421-9
• 发表时间: 2010-05-01
• 期刊: ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
• 影响因子: 4
• 作者: Asakawa, H.;Tsunoda, M.;Aizawa, Y.
• 通讯作者: Aizawa, Y.