title: Presynaptic inhibition of cerebellar GABAergic transmission by glutamate decarboxylase autoantibodies in progressive cerebellar ataxia.
abstract: Autoantibodies against glutamic acid decarboxylase (GAD) have been found in stiff-man syndrome, insulin dependent diabetes mellitus, and progressive cerebellar ataxia. A patient with progressive cerebellar ataxia is described who was positive for GAD autoantibodies, and had Sjögren's syndrome. Immunohistochemical studies using CSF and serum samples from the patient showed immunoreactivities in axon terminals of cerebellar GABAergic neurons. A whole cell patch clamp technique recording from rat cerebellar slices showed that the CSF, presumably through GAD autoantibodies, presynaptically inhibited GABAergic transmission. Intravenous administration of immunoglobulin failed to improve clinical symptoms and immunoreactivities examined after therapy. The findings suggest that GAD autoantibodies play a pathogenic part in reducing GABA release in in vitro slices.
authors.affiliation: Department of Neurology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takenoshita
authors.forename: M
authors.initials: M
authors.lastname: Shizuka-Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Mitoma
authors.forename: S
authors.initials: S
authors.lastname: Song
authors.forename: Y
authors.initials: Y
authors.lastname: Harigaya
authors.forename: Y
authors.initials: Y
authors.lastname: Igeta
authors.forename: M
authors.initials: M
authors.lastname: Yaguchi
authors.forename: K
authors.initials: K
authors.lastname: Ishida
authors.forename: M
authors.initials: M
authors.lastname: Shoji
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D002524:Cerebellar Ataxia / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D017729:Presynaptic Terminals / Q000276:immunology*; D009435:Synaptic Transmission / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase