HUNTINGTONS-DISEASE - THE NEUROEXCITOTOXIN ASPARTATE IS INCREASED IN PLATELETS AND DECREASED IN PLASMA

The neural degeneration observed in the striata of patients with Hunti ngton's disease (HD) can be reproduced by excitatory NMDA receptor ago nists such as aspartate and glutamate in striatal cell cultures and in striata of vertebrates injected with these substances. Therefore, we decided to investigate the role of aspartate and glutamate in HD. Aspa rtate, glutamate, glutamine, and phenylalanine were measured in platel ets and plasma of HD patients and age- and sex-matched healthy control s (C), using HPLC methods. In HD platelets the mean aspartate concentr ation was significantly (p < 0.01) increased (8.9 +/- 3.8 (SD) nmol/mg protein, n = 28) compared to C (4.6 +/- 1.4 (SD) nmol/mg protein, n = 24), whereas plasma aspartate was significantly (p < 0.01) decreased in HD (0.092 +/- 0.023 (SD) mg/dl, n = 16) versus C (0.179 +/- 0.109 ( SD) mg/dl, n = 21). The increase in platelet aspartate should be a dir ect or indirect consequence of the dominant gene defect in HD. It migh t therefore be present in neurons as well, especially since platelets share many characteristics with neurons. Hence, chronically increased release of aspartate with consecutive overstimulation of postsynaptic neurons via NMDA receptors might be responsible for the damage observe d in striatal target cells of corticostriatal glutamatergic and aspart atergic projection fibers in HD.