NEUROTRANSMISSION AND HUNTINGTONS-DISEASE

A discussion of the pathophysiology of Huntington's disease should be based on an up-to-date description of the central nervous system neuro transmitter abnormalities seen in this condition. Although the striatu m is selectively affected, an energy deficiency is consistently found in the cortex. Two current hypotheses are worthy of consideration, of which one involves exaggerated cortical input from glutaminergic neuro nes projecting to the striatum, and the other a primary mitochondrial abnormality. The main cortical abnormalities include depletion of GABA , glutamate, and acetylcholine; and elevations in dopamine and seroton in metabolic derivatives. In the striatum, decreases are found in the levels of GABA and other neurotransmitters, These working hypotheses m ust be reconciled with the discovery of huntingtin, the product of the abnormal gene, and with the selective accumulation within neurones of polyglutaminated compounds.