Comparison of Tissue Aspartoacylase Activity and Developmental Evolution Pattern

The level of aspartoacylase activity was measured in several brain regions in rats from newborn to adulthood. This study demonstrates that there was a differential expression of aspartoacylase activity, which not only varied with development but also showed regional variation in the induction of enzyme activity over time. Apart from the optic nerve, all areas of the brain had very low levels of activity at birth, with most tissues expressing enzyme levels at the limit of detection. The greatest developmental increase in expression of aspartoacylase was seen in white matter tracts such as the optic nerve with a five-fold increase from P1 to P21, followed by a significant reduction in adulthood. The largest rate of increase was seen after postnatal day 7. The brain stem and corpus callosum also showed similar trends, with accelerated expression seen after the seventh day of birth. Aspartoacylase activity in the cerebellum followed a similar profile but was much less marked. Gray matter such, as hippocampus, olfactory bulb and the cortex did not express much activity or show a developmental trend (see Figure 5). The largest differential in the expression of tissue aspartoacylase activity is seen between the optic nerve and the cortex at postnatal day 21 with an approximately 60-fold difference between the two regions. Aspartoacylase activity was determined in 'whole' cortex and compared to cortex 'stripped' of corpus callosum. There was a 18-fold difference between 'stripped' cortex and dissected corpus callosum (0.81 ± 0.05 |j.U), whereas there was only a 4-fold difference between 'whole' cortex (0.20 ± 0.05 |j.U) and 'stripped' cortex (0.05 ± 0.03 |j.U). Therefore unless the corpus callosum is dissected from the cortex, it leads to misleading levels of aspartoacylase activity. Moreover, the cortex, which shows the largest developmental increase in expression of NAA over a similar time-course37 had the lowest levels of aspartoacylase activity, and was in most cases at the limit of detection. The opposite was true for the optic nerve, which had the highest levels of aspartoacylase activity, but the lowest levels of NAA (see Figure 5).

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