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.
Ishida
Kazuyuki
K
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
Mitoma
Hiroshi
H
Mizusawa
Hidehiro
H
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