Modulation of monoaminergic and amino acid transmission as a means for therapeutic intervention in ataxia

In recent years, substantial progress has been made in understanding the organization and function of the cerebellum at the neuronal, synaptic, and molecular level. More than any other region of the brain, the cerebellum utilizes amino acids as its main excitatory and inhibitory transmitters. Excitatory amino acids, such as glutamate and aspartate, in addition to serving as chemical messengers, may also mediate neurodegenerative processes in human ataxic disorders. Of the monoamines, serotonin has been proposed as a neuromodulator in the cerebellum and is thought to play a role in the pathophysiology of ataxia in animal models, and human cerebellar disorders. These considerations raise the possibility that pharmacologic modification of amino acid and serotonergic transmission may provide a means for therapeutic intervention in ataxia.