Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias

Figure 2

Pathogenic actions of CSF IgGs from GAD65Ab-positive CA and human monoclonal GAD65Ab b78 in cerebellar slices prepared from rats and mice. (a) Electrical stimulation in the cerebellar cortex induces GABA-mediated inhibitory postsynaptic currents (IPSCs) and glutamate-mediated excitatory postsynaptic currents (EPSCs) in a PC. The CSF IgGs depressed IPSCs without affecting EPSCs. Two sweeps are superimposed. (b) Immunoreactivities of CSF IgGs were observed in the presynaptic terminals of GABAergic interneurons and not the postsynaptic PC. Large and small white arrows indicate punctate immunoreactivity in the rim of the somata and high density of immunoreactivity terminals in the initial segment of PC, respectively. Arrowhead indicates immunoreactivity along with dendritic shaft. (c) b78-induced impairment in GABA release: decreased amplitudes of miniature IPSCs, reduced GABA content in vesicles, and reduction of frequency of miniature IPSCs, and the release probability of GABAergic vesicles. Two sweeps (grey and black) are superimposed. Data are mean ± SEM of 12 experiments. These figures were modified from our previous references [7, 30, 31].

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