Biochemical Development of the Human Brain

Abstract

The development of the cholinergic system in the human forebrain, cerebral cortex and cerebellum was studied in post mortem material by estimating activity of choline acetyltransferase (CAT) and the binding capacity for quinuclidinyl benzilate (QNB) as markers for cholinergic nerve terminals and muscarinic receptors respectively; also the activity of acetylcholinesterase (AchE) was determined. The age periods were as follows (number of specimens in parentheses): fetal period, 18–22 weeks gestational age(GA; 8). perinatal period, 26–44 weeks GA (5–15 depending on brain part), early postnatal period, 2–15 months (4), and adult life, 58–70 years (4). Total protein and DNA were estimated in all specimens, and whole organ weights were obtained for the forebrain and most of the cerebellum specimens, allowing assessment of total organ parameters. Marked differences were observed in the ontogenesis of the cholinergic system in the cerebrum and the cerebellum. In the cerebral cortex and the forebrain from 18 weeks gestation towards term there was an increase in the concentration of CAT activity, which, however, had not reached adult concentrations at birth; on the other hand, receptor development was more advanced, since QNB binding site concentration reached adult levels by term. In sharp contrast, in the cerebellum maximal CAT activity was attained in the 26–42 weeks GA group. In comparison with the concentration of this presynaptic marker at that age period, the estimates in the postnatal samples were only 10–18%, the precipitous decline occurring during the early postnatal period. The highest concentration of the cholinergic ligand binding sites was also reached during gestation, but the peak was attained earlier (18–22 weeks GA) and the fall in concentration with age was less sharp. In contrast to the developmental changes in the concentration of the muscarinic receptor the affinity for the ligand was apparently the same throughout the age period studied. AchE activity in cerebral cortex increased with development to a level higher than that found in the adult, while the cerebellum was much richer in AchE and there was a modest developmental increase, the highest concentrations being found in adult cerebellum.