Studies on neurotransmitter markers and striatal neuronal cell density in Huntington's disease and dentatorubropallidoluysian atrophy.

Neurotransmitter abnormalities in the basal ganglia of individual "choreic" patients (9 cases of Huntington's disease-HD and 3 cases of dentatorubropallidoluysian atrophy-DRPLA) and 14 normal controls were investigated. Choline acetyltransferase activity in the striatum was decreased in approximately half the "choreic" patients. GABA concentration in the substantia nigra or in the globus pallidus was decreased in all "choreic" cases except one case of DRPLA. Substance P concentration was also reduced in the same nuclei as GABA except in one case of HD. These findings imply: cholinergic, GABAergic or substance P-related markers found in the basal ganglia of HD are not disease-specific but also found in the other "choreic" disorder, i.e. DRPLA; most prominent biochemical changes in HD would be a decrease of GABA in the basal ganglia. Correlation analysis of the markers in the basal ganglia and the striatal neurone densities of "choreic" patients (5 cases of HD and 3 cases of DRPLA) and 7 normal controls yielded positive correlation between GABA concentration in the substantia nigra and the globus pallidus, and the neuronal cell density in "small" cells in the striatum of normal control and HD. Positive correlation between substance P concentration and the striatal neurone density was only found in the substantia nigra. Choline acetyltransferase activity in the striatum was found to be positively correlated with the density of "large" cells in the striatum rather than that of "small" cells. In DRPLA there was no direct correlation between the values of the markers in the basal ganglia and the striatal neurone density. The decrease of transmitter markers without striatal cell loss in this particular choreic disorder could be regarded as a sequence of "biochemical degeneration" of striatal neurones. Based on these findings, the underlying mechanisms of choreic involuntary movements were briefly discussed.