analysis of abnormal neuronal excitability mediated by alpha-synuclein oligomer

α-突触核蛋白寡聚体介导的异常神经元兴奋性分析

• 批准号: 23591265
• 负责人: KENJI Yamamoto
• 金额: $ 2万
• 依托单位: Department of Clinical Research, National Hospital Organization Utano National Hospital
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591265/
• 关键词: αシヌクレイン; オリゴマー; パーキンソン病; レビー小体型認知症; カリウムチャンネル; カルシウム; 膜興奮性; パッチクランプ; ドーパミン; 神経変性; シナプス伝達

We examined the action of alpha-synuclein oligomers on neuronal excitabilities by injecting protein into pyramidal neurons in mouse cortical slices through whole-cell patch pipettes.Western blot analysis showed that the pipette solution including alpha-synuclein incubated with dopamine (aS+DA), had higher order oligomer. Intracellular application of aS+DA suppressed spike firing during current injection. Nimodipine and apamin blocked the effect of aS+DA on spike firing. aS+DA prolonged the duration of spike afterhyperpolarization (AHP) and increased the charge transfer carried by the current during AHP under current clamp, both of which were inhibited by apamin.These results suggest that alpha-synuclein oligomers suppress spike frequency by enhancing AHP, and apamin-sensitive SK-type calcium-activated potassium channel is involved with the enhancement. This mechanism may cause the downregulation of neocortical activities in Parkinson's disease and dementia with Lewy bodies.

我们通过全细胞贴片管将蛋白质注入小鼠皮层脑片锥体神经元，研究了α-突触核蛋白寡聚体对神经元兴奋性的影响。Western印迹分析表明，含有α-突触核蛋白与多巴胺(AS+DA)孵育的吸管溶液具有更高阶次的寡聚体。细胞内应用AS+DA可抑制电流注入过程中的峰电位放电。尼莫地平和阿帕明可阻断AS+DA对放电的影响。As+DA可延长电流钳下动作电位的峰后超极化(AHP)持续时间，增加电流携带的电荷转移，这两种作用均可被Ap抑制，提示α-突触核蛋白寡聚体通过增强AHP而抑制AHP，Ap敏感的SK-型钙激活钾通道参与了AHP的增强。这一机制可能导致帕金森病和路易体痴呆的新皮质活动下调。

项目成果

Role of Brain MRI Apparent Diffusion Coefficient (ADC) in the Differential Diagnosis of Parkinson's Disease (PD) and Progressive Supranuclear Palsy (PSP)

脑 MRI 表观弥散系数 (ADC) 在帕金森病 (PD) 和进行性核上性麻痹 (PSP) 鉴别诊断中的作用

• 发表时间: 2011
• 作者: Umemura A;Oeda T;Kohsaka M,Tomita S;Hayashi R;Yamamoto K;Sawada H
• 通讯作者: Sawada H

Down-regulation of spike frequency by alpha-synuclein oligomer

α-突触核蛋白寡聚体下调尖峰频率

• 发表时间: 2014
• 作者: 山本兼司;山川健太郎;澤田秀幸
• 通讯作者: 澤田秀幸

Suppression of spike frequency by α-Synuclein oligomer in neocortical pyramidal neurons

α-突触核蛋白寡聚物对新皮质锥体神经元尖峰频率的抑制

• 发表时间: 2013
• 作者: Tatsufumi Murakami;Atsushi Iwanaga;Yoshinao Ogawa;Yoshiaki Fujita; Eiji Sato;Hironori Yoshitomi;Yoshihide Sunada;Akihiro Nakamura;Yamamoto K et al.
• 通讯作者: Yamamoto K et al.

Brain MRI apparent diffusion co-efficient (ADC) in Parkinson's disease with dementia

帕金森病伴痴呆的脑部 MRI 表观弥散系数 (ADC)

• 发表时间: 2012
• 作者: Umemura A;Oeda T;Kohsaka M,Tomita S;Hayashi R;Yamamoto K;Sawada H
• 通讯作者: Sawada H

αシヌクレインオリゴマーは大脳皮質錐体細胞の発火頻度を低下させる

α-突触核蛋白寡聚物降低大脑皮层锥体细胞的放电频率

• 发表时间: 2013
• 作者: 山本兼司;山川健太郎;澤田秀幸
• 通讯作者: 澤田秀幸