Abstract
Stiff person syndrome with auto-antibodies against amphiphysin is characterized by muscular stiffness, spasms, and anxiety which is a less appreciated core symptom. Here, we report that intrathecal application of purified immunoglobulin G-antibodies against amphiphysin from one patient induce anxiety behavior in rats. Immunostaining demonstrated binding of anti-amphiphysin antibodies to brain structures which are associated with anxiety disorders, such as the amygdala. We propose that antibody-mediated amphiphysin deficiency may account for anxiety behavior in stiff person syndrome via presynaptic dysregulation of GABAergic pathways.
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Acknowledgments
We thank P. De Camilli for providing the cDNA clone encoding for amphiphysin protein. L. Biko, S. Hellmig, B. Dekant, H. Bruenner, and H. Wetzstein provided expert technical assistance in animal experiments, histology, and IgG preparations. The authors declare no competing financial interests. This work was supported by the Deutsche Forschungsgemeinschaft SFB 581 [TP A7 and HE 2621/4-1], SFB TRR 58 [Z02], KFO 125 [TP4], RTG 1256/2, RE1632/5, by the IZKF Würzburg, and by intramural University Research Funds.
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C. Geis and B. Grünewald contributed equally to this work.
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Geis, C., Grünewald, B., Weishaupt, A. et al. Human IgG directed against amphiphysin induces anxiety behavior in a rat model after intrathecal passive transfer. J Neural Transm 119, 981–985 (2012). https://doi.org/10.1007/s00702-012-0773-3
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DOI: https://doi.org/10.1007/s00702-012-0773-3