Development of An Animal Model of the Lambert-Eaton Myasthenic Syndrome

兰伯特-伊顿肌无力综合征动物模型的开发

基本信息

批准号：
10557232
负责人：
KIRINO Yutaka
金额：
$ 8.64万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

1. Development of LES animal model by immunization with electric organ synaptosomes. Mice immunized with synaptosomes isolated from the electric organ of Japanese electric ray displayed a symptom typical for the Lambert, Eaton Myasthenic Syndrome (LES) : a decrease in the quantal content of transmitter release was observed at the neuromuscular junction (NMJ) in the diaphragm from the immunized mice.2. Development of LES animal model by passive immunization. Mice were passively immunized by injection of the serum from the actively immunized rabbits with synaptosomes. Again a decrease in the quantal content was observed, indicating that LES animal model was successfully generated.3. Effect of the serum/IgG from IES patients to P-type Ca channels of SCLC cultured cells. The presence of P-type Ca channels of small cell lung carcinoma (SCLC) cells, which are a potential candidate for the auto-immunogen implicated in the etiology of LES, was examined by Ca imaging technique. About 20% of the cytoplasmic Ca increase induced by high KィイD1+ィエD1 stimulation was estimated to be due to P-type Ca channels as evidenced by the inhibition with a P-type specific inhibitor Agatoxin IVA. Then, the effect of LES serum to cytoplasmic Ca rise was examined but no significant inhibition was detected.4. Effect of an acetylcholine esterase (ACE) inhibitor to the synaptic transmission at NMJ. An ACE inhibitor donepezil chloride, which is a sole effective drug for Alzheimer's disease now on market, increased the quantal content at the diaphragm NMJ. Furthermore, it was synergetic with 4-aminopyridine that is now the major medicine for LES but has a severe side effect.5. Attempt to visualize internalization of P-type Ca channels with LES antibody. The down-regulation of P-type Ca channels with LES auto-antibody may be due to the internalization, which we attempted to visualize, if any. However, it was not successful so far.

1.通过电器官突触体免疫建立LES动物模型用从日本电鳐的电器官分离的突触体免疫的小鼠表现出兰伯特、伊顿肌无力综合症(LES)的典型症状：递质含量减少。免疫小鼠膈肌神经肌肉接头(NMJ)处观察到释放。2．被动免疫LES动物模型的建立。将主动免疫家兔血清注射突触体进行被动免疫，再次观察到其含量减少，表明成功建立LES动物模型。 3．IES患者血清/IgG对P-的影响。 SCLC 培养细胞的 P 型 Ca 通道的存在，是 LES 病因学中涉及的自身免疫原的潜在候选者。通过 Ca 成像技术检查，高 KiiD1+KiiD1 刺激诱导的细胞质 Ca 增加估计约 20% 是由于 P 型 Ca 通道，如 P 型特异性抑制剂 Agatoxin IVA 的抑制所证明的。检测了LES血清对细胞质Ca升高的影响，但没有检测到乙酰胆碱酯酶(ACE)抑制剂对NMJ突触传递的影响。氯化多奈哌齐是目前市场上治疗阿尔茨海默氏病的唯一有效药物，它增加了膈肌 NMJ 的含量。此外，它与目前 LES 主要药物 4-氨基吡啶有协同作用，但具有严重的副作用。 5。尝试用 LES 抗体观察 P 型 Ca 通道的内化 LES 自身抗体对 P 型 Ca 通道的下调可能是由于内化所致。我们试图想象，如果有的话，但到目前为止还没有成功。

项目成果

期刊论文数量（79）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Azusa Nakagawa-Inoue: "Odorant-evoked Increase in Cytosolic Free Calcium in Cultured Anntenal Neurons of Blowflies" Zool.Sci.15. 661-666 (1998)

Azusa Nakakawa-Inoue：“气味引起的绿蝇培养触角神经元中胞质游离钙的增加”Zool.Sci.15。

DOI：
发表时间：
期刊：
影响因子：
0
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通讯作者：

Lee, D-S.: "Phospholipid translocation from outer to inner leaflet of synaptic vesicle membranes isolated from the electric organ of japanese electric ray Narke japanica"J. Biochem.. 124. 798-803 (1998)

Lee，D-S.：“从日本电鳐 Narke japanica 的电器官中分离出的突触小泡膜的磷脂从外叶到内叶的易位”J。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

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