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Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats

Please always quote using this URN: urn:nbn:de:bvb:20-opus-140506
  • Background: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/PrincipalBackground: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/Principal Findings: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11) C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. Conclusion/Significance: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.show moreshow less

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Metadaten
Author: Christian Geis, Andreas Weishaupt, Benedikt Grünewald, Thomas Wultsch, Andreas Reif, Manfred Gerlach, Ron Dirkx, Michele Solimena, Klaus V Toyka, Franco Folli, Daniela Perani, Manfred Heckmann, Claudia Sommer
URN:urn:nbn:de:bvb:20-opus-140506
Document Type:Journal article
Faculties:Medizinische Fakultät / Neurologische Klinik und Poliklinik
Language:English
Parent Title (English):Plos One
Year of Completion:2011
Volume:6
Issue:2
Pagenumber:e16775
Source:PLoS ONE 6(2):e16775. doi:10.1371/journal.pone.0016775
DOI:https://doi.org/10.1371/journal.pone.0016775
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:65-kda isoform; Glutamic-acid decarboxylase anxiety; antibodies; anxiety; autoantibodies; disorder; fear memory; neurons; presynaptic inhibition; spinal-cord-injury
Release Date:2018/11/05
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung