Stiff person syndrome associated anti-amphiphysin antibodies reduce GABA associated [Ca2+]i rise in embryonic motoneurons

被引:19
作者
Geis, C. [1 ]
Beck, M. [1 ]
Jablonka, S. [2 ]
Weishaupt, A. [1 ]
Toyka, K. V. [1 ]
Sendtner, M. [2 ]
Sommer, C. [1 ]
机构
[1] Univ Wurzburg, Dept Neurol, D-97080 Wurzburg, Germany
[2] Univ Wurzburg, Inst Clin Neurobiol, D-97080 Wurzburg, Germany
关键词
Stiff person syndrome; Amphiphysin; Autoantibodies; Calcium imaging; Chloride potential; Na+/K+/2Cl(2-) cotransporter; COATED VESICLES; BOVINE BRAIN; CORTICAL-NEURONS; RAT MOTONEURONS; BREAST-CANCER; RECEPTORS; ENDOCYTOSIS; AUTOIMMUNITY; INHIBITION; EXPRESSION;
D O I
10.1016/j.nbd.2009.07.011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Autoantibodies to the synaptic protein amphiphysin play a crucial pathogenic role in paraneoplastic stiff-person syndrome. Impairment of GABAergic inhibition is the presumed pathophysiological mechanism by which these autoantibodies become pathogenic. Here we used calcium imaging on rat embryonic motor neurons to investigate whether antibodies to amphiphysin directly hinder GABAergic signaling. We found that the immunoglobulin G fraction from a patient with stiff-person syndrome, containing high titer antibodies to amphiphysin and inducing stiffness in rats upon passive transfer, reduced GABA-induced calcium influx in embryonic motor neurons. Depletion of the anti-amphiphysin fraction from the patient's IgG by selective affinity chromatography abolished this effect, showing its specificity for amphiphysin. Quantification of the surface expression of the Na+/K+/2Cl(2-) cotransporter revealed a reduction after incubation with anti-amphiphysin IgG, which is concordant with a lower intracellular chloride concentration and thus impairment of GABA mediated calcium influx. Thus, anti-amphiphysin antibodies exert a direct effect on GABA signaling, which is likely to contribute to the pathogenesis of SPS. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:191 / 199
页数:9
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