The molecular imaging study for the mechanism of the Deep brain stimulation in MPTP treated monkey

MPTP治疗猴深部脑刺激机制的分子影像研究

• 批准号: 20791025
• 负责人: FANG Xin
• 金额: $ 2.66万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20791025/
• 关键词: 機能脳神経外科学; パーキンソン氏病; 脳深部電気刺激術; 視床下核; PET; ドパミン受容体; 脳血流; パーキソンソ氏病; 分子イメージング; PET計測; Tracer; ドーパミン受容体

To clarify the mechanism of the deep brain stimulation (DBS), we performed the PET study in the MPTP treated monkey by the tracer of H_2^<15>O to measure the regional cerebral blood flow (rCBF). We found the rCBF of medial superior frontal gyrus, supplementary motor cotex, superior parietal lobule and thalamus in the DBS side, the anterior cerebellar cortex in the contralateral side significantly increased, which gave an evidence that the mechanism of STN-DBS lies in the correcting the overactivation of motor controlling network.In order to clarify the dynamic variation pattern of dopamine transporter (DAT) and D^2 receptor after the dopamine depletion, which greatly influences the efficiency of DBS, we studied the variation of pre-synaptic DA transporter and post-synaptic D^2-like receptor in nigrostriatal DA system using binding assay, behavioral test and a small animal PET. Our data showed that there was a same tendency of the striatal DA transporter decrease both in MFB lesion rats and striatal lesion rats 4 weeks after lesion, however, it showed increase (up-regulation) of D^2-like receptor in the MFB lesion rats, whereas showed decrease (down-regulation) in the striatal lesion rat. This finding strongly indicated the dynamic variation pattern of DAT and D^2 receptor after the dopamine depletion should be taken into account in the molecular imaging study in PD animal models.

为了阐明深脑刺激（DBS）的机制，我们通过H_2^<15> O的示踪剂在MPTP治疗的MPTP研究中进行了PET研究，以测量区域脑血流（RCBF）。我们发现，DBS侧的内侧上额回，辅助运动cotex，辅助运动cotex，上顶叶和丘脑，前侧的前小脑皮层显着增加，这证明了STN-DBS的机制在于校正DID DATID的机制。多巴胺消耗后的D^2受体极大地影响了DBS的效率，我们研究了使用结合测定，行为测试，小动物宠物和一个小动物宠物，研究了突触前DA转运蛋白和突触后D^2样受体的变化。我们的数据表明，在病变后4周，MFB病变大鼠和纹状体病变大鼠中纹状体DA转运蛋白的趋势均降低，但是，MFB病变大鼠的D^2样受体的增加（上调），而在（下降）中均显示（下调）。这一发现强烈表明在PD动物模型的分子成像研究中应考虑多巴胺消耗后Dat和D^2受体的动态变异模式。

项目成果

H_2^<15>Oを用いて、MPTPサルにおける脳深部電気刺激下、脳血流、のPET測定

H_2^<15>O PET测量MPTP猴深部脑电刺激下脑血流量

• 发表时间: 2008
• 作者: 方欣;杉山憲嗣;赤嶺壮一;難波宏樹;尾上浩隆
• 通讯作者: 尾上浩隆

H215Oを用いて、MPTPサルにおける脳深部電気刺激下

使用 H215O 对 MPTP 猴子进行深部脑电刺激

• 发表时间: 2008
• 作者: 方欣;杉山憲嗣;赤嶺壮一;難波宏樹;宿里充穂;横山ちひろ;水間広;塚田秀夫;尾上浩隆
• 通讯作者: 尾上浩隆

パーキンソンモデルラットの片側線条体破壊モデルと片側MFB破壊モデルの違いーPETによるD2受容体活性の経時的変化測定

帕金森病模型大鼠单侧纹状体破坏模型与单侧MFB破坏模型的差异——PET测量D2受体活性时程变化

• 发表时间: 2010
• 作者: 孫偉;杉山憲嗣;方欣;山口博司;赤嶺壮一;間賀田泰寛;難波宏樹
• 通讯作者: 難波宏樹

The difference of D2 receptor alteration between the unilateral striatal lesion and complete medial forebrain bundle lesion by 6-hydroxydopamine in rats, a PET study

6-羟基多巴胺对大鼠单侧纹状体损伤和完全内侧前脑束损伤D2受体改变的差异的PET研究

• 发表时间: 2008
• 作者: Sun W;Fang X;Sugiyama K;Akamine S;Magata Y;Umemura K;Hokamura K;Yamaguchi H;Namba H
• 通讯作者: Namba H

The dynamic variation of D2 receptor between the unilateral striatal and complete medial forebrain bundle in early and late stage by 6-hydroxydopamine in rats

6-羟基多巴胺对大鼠单侧纹状体和完整内侧前脑束早期和晚期D2受体的动态变化

• 发表时间: 2009
• 作者: 孫偉;杉山憲嗣;方欣;山口博司;赤嶺壮一;間賀田泰寛;難波宏樹
• 通讯作者: 難波宏樹