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.

Biochemical development of the human brain. III. Benzodiazepine receptors, free Y‐aminobutyrate (GABA) and other amino acids

“…The relatively delayed ontogencsis of BZP receptors in the human brain, compared with the rat [Candy and Martin, 1979;Palacios et al, 19791 or mouse [Mallorga et al, 19801, is not associated with a species difference in the relative densities of BZP and GABA receptors in the adult [Brooksbank et al, 1981;Placheta and Karobath, 19791, and the finding should be considered in the light of the evidence that only a limited proportion of GABA receptors are closely linked with BZP aForebrain. hValues for GABA in developing cerebellum of the rat are not available, but in dog and cat the ontogenetic accretion of GABA in cerebellum resembles that in cerebral cortex (for reviews see Agrawal and Himwich [1970] and Davis and Himwich [1973]).…”

“…The pattern of accumulation of [3H]muscimol binding sites in both brain parts, and their advanced development in relation to the GAD activity in the cerebral cortex, are similar in the two species. However, in the human cerebellum the development of GABA receptors is retarded in comparison with that of GAD activity; this is in contrast to their ontogenetic relationship in the cerebellum of the rat [Brooksbank et al, 1981;Palacios et al, 1979;Patel et al, 19801. Thus.…”