Huntington's Chorea: Post Mortem Activity of Enzymes Involved in Cerebral Glucose Metabolism

Abstract

Abstract— The loss of at least two different cell types in the basal ganglia of the choreic brain led us to examine the activity of enzymes involved in the metabolism of glucose. Cellular ATPase, HK, G6‐PDH, PFK., LDH, GDH were measured. Post mortem stability studies indicated that these enzymes were more unstable in human brain than mouse brain. The most stable enzyme was GDH. HK activity appeared to increase after freezing, suggesting release from another compartment. PFK and G6‐PDH activity decreased by 70% over the usual time and temperature period for autopsy. In the autopsied brain tissue we were still able to measure significant activities that allowed us to determine the distribution of these enzymes and the similar post mortem handling of control and choreic brain allowed us to compare these two groups. The activity of HK and G6‐PDH was higher in the frontal cortex than in the basal ganglia. Ouabain insensitive ATPase and PFK were higher in the basal ganglia than the frontal cortex. GDH activity, an enzyme that is very active in glial cells, was increased in the choreic globus pallidus, an area with a very high glial to neuronal cell ratio. Although there was a wide variation in PFK activity that appeared to be related to the pre‐mortem clinical state there was a significant decrease in PFK activity in the putamen of choreic post mortem brain when compared to controls. These findings do not indicate an absolute defect in any of the enzymes studied in choreic brain but further studies might prove worthwhile.

Glutamate Dehydrogenase in Human Brain: Regional Distribution and Properties

“…Furthermore, in our experiments human brain GDH did not appear to be affected either by the interval from death to postmortem examination, o r by storage at -20°C. These findings of GDH stability in autopsy human brain are in agreement with those reported by Bird et al (1977).…”

“…When the values were expressed as nmol/min/mg protein, the regional distribution pattern was similar with a range from 103 to 377. Our values of GDH activity in human brain fell within the range reported for rat brain (Filla et al, 1984;Leong and Clark, 1984) and were slightly higher than those reported by Johnson (1972) for cat brain, and by Bird et al (1977) for human brain.…”

Cortical Pyramidal Neurone Loss May Cause Glutamatergic Hypoactivity and Cognitive Impairment in Alzheimer's Disease: Investigative and Therapeutic Perspectives

“…However, this enzyme is particularly susceptible to the effect of postmortem delay, agonal state. and tissue freezing (Bird et al, 1977: Iwangoff et al, 1980 and the results could not be interpreted with confidence. Subsequent measurements in biopsied neocortex revealed no consistent reductions in the activity of this enzyme in AD (Sims et al.…”

Towards an Understanding of Energy Impairment in Huntington’s Disease Brain

“…Similarly in the occiput of affected individuals, onset of visual stimulation fails to increase P i /ATP, PCr/ATP or P i /PCr ratios or lactate accumulation, as observed in control subjects [ 66 ]. The glycolytic enzyme phosphofructokinase was diminished in the post mortem HD caudate and putamen, but not in cortex [ 68 ] ( Fig. 1 ).…”