Top

Published in:

01-03-2015 | Translational Neurosciences - Short communication

Stiff person-syndrome IgG affects presynaptic GABAergic release mechanisms

Authors: Christian Werner, Holger Haselmann, Andreas Weishaupt, Klaus V. Toyka, Claudia Sommer, Christian Geis

Published in: Journal of Neural Transmission | Issue 3/2015

Abstract

The majority of patients with stiff person-syndrome (SPS) are characterized by autoantibodies to glutamate decarboxylase 65 (GAD65). In previous passive-transfer studies, SPS immunoglobulin G (IgG) induced SPS core symptoms. We here provide evidence that SPS-IgG causes a higher frequency of spontaneous vesicle fusions. Sustained GABAergic transmission and presynaptic GABAergic vesicle pool size remained unchanged. Since these findings cannot be attributed to anti-GAD65 autoantibodies alone, we propose that additional autoantibodies with so far undefined antigen specificity might affect presynaptic release mechanisms.

Allen C, Stevens CF (1994) An evaluation of causes for unreliability of synaptic transmission. Proc Natl Acad Sci USA 91:10380–10383CrossRefPubMedCentralPubMed

Bergado-Acosta JR, Muller I, Richter-Levin G, Stork O (2014) The gaba-synthetic enzyme gad65 controls circadian activation of conditioned fear pathways. Behav Brain Res 260:92–100CrossRefPubMed

Butler MH et al (2000) Autoimmunity to gephyrin in stiff-man syndrome. Neuron 26:307–312CrossRefPubMed

Byts N, Samoylenko A, Fasshauer T, Ivanisevic M, Hennighausen L, Ehrenreich H, Siren AL (2008) Essential role for stat5 in the neurotrophic but not in the neuroprotective effect of erythropoietin. Cell Death Differ 15:783–792CrossRefPubMed

Chang T et al (2013) Immunization against gad induces antibody binding to gad-independent antigens and brainstem GABAergic neuronal loss. PLoS One 8:e72921CrossRefPubMedCentralPubMed

Chattopadhyay S, Ito M, Cooper JD, Brooks AI, Curran TM, Powers JM, Pearce DA (2002) An autoantibody inhibitory to glutamic acid decarboxylase in the neurodegenerative disorder batten disease. Hum Mol Genet 11:1421–1431CrossRefPubMed

Edwards FA, Konnerth A, Sakmann B (1990) Quantal analysis of inhibitory synaptic transmission in the dentate gyrus of rat hippocampal slices: a patch-clamp study. J Physiol 430:213–249CrossRefPubMedCentralPubMed

Galldiks N, Thiel A, Haense C, Fink GR, Hilker R (2008) 11c-flumazenil positron emission tomography demonstrates reduction of both global and local cerebral benzodiazepine receptor binding in a patient with stiff person syndrome. J Neurol 255:1361–1364CrossRefPubMed

Geis C et al (2010) Stiff person syndrome-associated autoantibodies to amphiphysin mediate reduced GABAergic inhibition. Brain 133:3166–3180CrossRefPubMed

Geis C et al (2011) Human stiff-person syndrome igg induces anxious behavior in rats. PLoS One 6:e16775CrossRefPubMedCentralPubMed

Hansen N, Grunewald B, Weishaupt A, Colaco MN, Toyka KV, Sommer C, Geis C (2013) Human stiff person syndrome igg-containing high-titer anti-gad65 autoantibodies induce motor dysfunction in rats. Exp Neurol 239:202–209CrossRefPubMed

Henningsen P, Meinck HM (2003) Specific phobia is a frequent non-motor feature in stiff man syndrome. J Neurol Neurosurg Psychiatry 74:462–465CrossRefPubMedCentralPubMed

Kash SF, Johnson RS, Tecott LH, Noebels JL, Mayfield RD, Hanahan D, Baekkeskov S (1997) Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci USA 94:14060–14065CrossRefPubMedCentralPubMed

Kraushaar U, Jonas P (2000) Efficacy and stability of quantal gaba release at a hippocampal interneuron-principal neuron synapse. J Neurosci 20:5594–5607PubMed

Manto MU, Laute MA, Aguera M, Rogemond V, Pandolfo M, Honnorat J (2007) Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases. Ann Neurol 61:544–551CrossRefPubMed

Martin JA, Hu Z, Fenz KM, Fernandez J, Dittman JS (2011) Complexin has opposite effects on two modes of synaptic vesicle fusion. Curr Biol 21:97–105CrossRefPubMedCentralPubMed

Mata S, Muscas GC, Cincotta M, Bartolozzi ML, Ambrosini S, Sorbi S (2010) Gad antibodies associated neurological disorders: incidence and phenotype distribution among neurological inflammatory diseases. J Neuroimmunol 227:175–177CrossRefPubMed

Pang ZP, Bacaj T, Yang X, Zhou P, Xu W, Sudhof TC (2011) Doc2 supports spontaneous synaptic transmission by a ca(2+)-independent mechanism. Neuron 70:244–251CrossRefPubMedCentralPubMed

Raju R et al (2006) Autoimmunity to gabaa-receptor-associated protein in stiff-person syndrome. Brain 129:3270–3276CrossRefPubMed

Ramirez DM, Khvotchev M, Trauterman B, Kavalali ET (2012) Vti1a identifies a vesicle pool that preferentially recycles at rest and maintains spontaneous neurotransmission. Neuron 73:121–134CrossRefPubMedCentralPubMed

Schindelin J et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682CrossRefPubMed

Seidenbecher T, Laxmi TR, Stork O, Pape HC (2003) Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval. Science 301:846–850CrossRefPubMed

Solimena M (1998) Vesicular autoantigens of type 1 diabetes. Diabetes Metab Rev 14:227–240CrossRefPubMed

Solimena M, Folli F, Denis-Donini S, Comi GC, Pozza G, De Camilli P, Vicari AM (1988) Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type i diabetes mellitus. N Engl J Med 318:1012–1020CrossRefPubMed

Sommer C, Weishaupt A, Brinkhoff J, Biko L, Wessig C, Gold R, Toyka KV (2005) Paraneoplastic stiff-person syndrome: passive transfer to rats by means of igg antibodies to amphiphysin. Lancet 365:1406–1411CrossRefPubMed

Tian N, Petersen C, Kash S, Baekkeskov S, Copenhagen D, Nicoll R (1999) The role of the synthetic enzyme gad65 in the control of neuronal gamma-aminobutyric acid release. Proc Natl Acad Sci USA 96:12911–12916CrossRefPubMedCentralPubMed

Vianello M, Tavolato B, Armani M, Giometto B (2003) Cerebellar ataxia associated with anti-glutamic acid decarboxylase autoantibodies. Cerebellum 2:77–79. doi:10.1080/14734220309432 CrossRefPubMed

Walter AM, Groffen AJ, Sorensen JB, Verhage M (2011) Multiple Ca2⁺ sensors in secretion: teammates, competitors or autocrats? Trends Neurosci 34:487–497CrossRefPubMed

Title: Stiff person-syndrome IgG affects presynaptic GABAergic release mechanisms
Authors: Christian Werner
Holger Haselmann
Andreas Weishaupt
Klaus V. Toyka
Claudia Sommer
Christian Geis
Publication date: 01-03-2015
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 3/2015
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-014-1268-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Stiff person-syndrome IgG affects presynaptic GABAergic release mechanisms

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2015

Effects of a short-term reduction in brain serotonin synthesis on the availability of the soluble leptin receptor in healthy women

Blepharospasm: long-term treatment with either Botox®, Xeomin® or Dysport®

Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice

Patients with mild cognitive impairment have an abnormal upper-alpha event-related desynchronization/synchronization (ERD/ERS) during a task of temporal attention

Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents

Correlations between plasma levels of amino acids and nonmotor symptoms in Parkinson’s disease