Presynaptic impairment of cerebellar inhibitory synapses by an autoantibody to glutamate decarboxylase.
Glutamic acid decarboxylase (GAD), the enzyme responsible for converting glutamate to gamma-aminobutyric acid (GABA), is a target of humoral autoimmunity in stiff-man syndrome and subacute cerebellar ataxia. Recently, we found that an anti-GAD autoantibody in the CSF of an ataxic patient selectively suppressed GABA-mediated transmission on cerebellar Purkinje cells without affecting glutamate-mediated transmission. Here, we examine the mechanism by which the autoantibody impaired the inhibitory transmission, using immunohistochemistry and whole-cell recording in rat cerebellar slices. The present results indicate that CSF immunoglobulins prepared from an ataxic patient acted on the presynaptic terminals of GABAergic interneurons and decreased GABA release onto Purkinje cells.
Mitoma
H
H
Mitoma Neurological Clinic, 1-2-10 Minami-Ikebukuro, Toshima-ku, Tokyo, Japan.
Song
S Y
SY
Ishida
K
K
Yamakuni
T
T
Kobayashi
T
T
Mizusawa
H
H
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002524:Cerebellar Ataxia / Q000276:immunology / Q000503:physiopathology; D002525:Cerebellar Cortex / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D017729:Presynaptic Terminals / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D011689:Purkinje Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D064030:S100 Calcium Binding Protein G; D016750:Stiff-Person Syndrome / Q000276:immunology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001323:Autoantibodies; D064026:Calbindins; D002135:Calcium-Binding Proteins; D018756:GABA Antagonists; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D002118:Calcium; D001640:Bicuculline