Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies
Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies
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DOI：
10.1002/ana.10451
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发表时间：
2003-03-01
影响因子：
11.2
通讯作者：
De Zeeuw, CI
中科院分区：
文献类型：
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作者：
Coesmans, M;Smitt, PAS;De Zeeuw, CI
霍奇金病患者可由于产生针对mGluR 1的自身抗体（mGluR 1-Abs）而发展为副肿瘤性小脑共济失调。然而，其运动协调缺陷的病理生理机制仍有待阐明。在这里，我们表明，从患者的血清纯化的IgG的应用程序的小鼠小脑切片急性降低浦肯野细胞的基础活性，而应用程序的小鼠在体内的绒球引起急性干扰的表现，他们的代偿性眼球运动。此外，mGluR 1-Abs阻断培养的小鼠浦肯野细胞中长期抑郁的诱导，而患者的小脑运动学习行为受到影响，因为他们显示出对扫视眼球运动的适应受损。最后，尸检分析的小脑的副肿瘤性小脑共济失调患者表明，浦肯野细胞的数量显着减少了约三分之二相比，三个控制。我们的结论是，针对mGluR 1的自身抗体可以导致小脑运动协调缺陷的组合所造成的快速影响的急性和塑性反应的浦肯野细胞和慢性退行性影响。
Patients with Hodgkin's disease can develop paraneoplastic cerebellar ataxia because of the generation of autoantibodies against mGluR1 (mGluR1-Abs). Yet, the pathophysiological mechanisms underlying their motor coordination deficits remain to be elucidated. Here, we show that application of IgG purified from the patients' serum to cerebellar slices of mice acutely reduces the basal activity of Purkinje cells, whereas application to the flocculus of mice in vivo evokes acute disturbances in the performance of their compensatory eye movements. In addition, the mGluR1-Abs block induction of long-term depression in cultured mouse Purkinje cells, whereas the cerebellar motor learning behavior of the patients is affected in that they show impaired adaptation of their saccadic eye movements. Finally, postmortem analysis of the cerebellum of a paraneoplastic cerebellar ataxia patient showed that the number of Purkinje cells was significantly reduced by approximately two thirds compared with three controls. We conclude that autoantibodies against mGluR1 can cause cerebellar motor coordination deficits caused by a combination of rapid effects on both acute and plastic responses of Purkinje cells and chronic degenerative effects.