Reversibility of cerebellar GABAergic synapse impairment induced by anti-glutamic acid decarboxylase autoantibodies.
Anti-glutamic acid decarboxylase autoantibodies (GAD-Abs) are found in some patients with cerebellar ataxia. We reported previously that CSF IgGs depress cerebellar GABAergic synaptic transmissions by a presynaptic mechanism. Using whole-cell recordings from rat cerebellar slices, we found in the present study that CSF IgG-induced depressive effects were abolished by absorption of GAD-Abs using recombinant GAD. Furthermore, forskolin, an activator of cAMP, recovered the CSF IgG-induced reduction of GABA release. Our results provide evidence that GAD-Abs in the CSF elicited physiopathological effects on cerebellar GABA synapses in vitro and that such synaptic impairment was reversible.
Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. k-ishida@iom.twmu.ac.jp
Kazuyuki
K
Ishida
Hiroshi
H
Mitoma
Hidehiro
H
Mizusawa
D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D002524:Cerebellar Ataxia / Q000134:cerebrospinal fluid / Q000276:immunology; D002531:Cerebellum / Q000166:cytology*; D005576:Colforsin / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D013569:Synapses / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007074:Immunoglobulin G; D005576:Colforsin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase