Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias

Table 1

Summary of effects of polyclonal and monoclonal GAD65Ab in vitro and in vivo.

		SPS GADAb	CA GADAb	b78	b96.11
In vitro	GABA synapse response in slices	Not done	Inhibition	Inhibition	Transient inhibition
	Association of GAD65 with GABAergic vesicles	Not done	Not done	Impairment	No effect
	Enzyme activity	Inhibition	No effect	Inhibition	No effect
In vivo	Glycerol turnover	No effect	Reduction	Reduction	No effect
	Corticomotor response	No effect	Impairment	Strong impairment	Impairment
	Cerebellar inhibition of MEPs	No effect	Decrease	Strong impairment	Decrease
	Premotor facilitations on MEPs	Not done	Not done	Impairment	No effect
	Conditioned eyelid responses	Not done	Not done	Impairment	No effect
	Gait	Not done	Not done	Ataxic	No effect

Glycerol turnover reflects membrane turnover as a result of exocytosis of GABA-containing vesicles [26].
Corticomotor response: the preceding trains of repetitive stimuli to peripheral nerve potentiate the amplitude of motor evoked potential (MEP) in normal controls.
Cerebellar inhibition on MEPs: when the cerebellum is stimulated prior to motor cortex stimulation, MEP decreases in amplitude in normal controls.
Premotor facilitation on MEPs: when trains of stimuli are delivered to the prefrontal cortex, the paired pulses ratio (conditioned MEP/unconditioned MEP) increases in normal controls.
These protocols examine cerebellar modulations on motor cortex excitability [7, 25, 26].
Classical conditioning of eyelid responses was performed. A short or long tone was used as the conditioning stimulus, and electrical shock was used as non-conditioning stimulus. The learning process of eyelid response is mediated by the cerebellum. Conditioned eyelid responses evoked in b78 mice were smaller than in control mice [7].
These results are summarized from [7, 26].