Biochemical development of the human brain. II. Some parameters of the GABA-ergic system

The development of the gamma-aminobutyrate (GABA)-ergic system in the human cerebral cortex and cerebellum was studied in post mortem specimens, by estimating the activity of glutamate decarboxylase (GAD) and the binding capacity for muscimol as markers of GABA-ergic nerve terminals and GABA receptors respectively. The age periods studied were as follows (number of specimens in parentheses): fetal period, 17--24 and 28 weeks, gestational age (GA) (15); perinatal period, 26--42 weeks GA (9); postnatal period, 43--56 and 74 weeks GA (11); adult life, 26, 47, 57--73 years (9). Total protein and DNA were estimated in all specimens. Differences between the cerebral cortex and the cerebellum in the ontogenesis of the GABA-ergic system were revealed. In the cerebral cortex, GAD-specific activity increased progressively during development, but at term had only reached approximately 20% of the adult value, and the trend in the postnatal specimens indicated that the adult level is not reached until some time after 60 weeks GA. The concentration of muscimol binding sites, on the other hand, rose more rapidly than GAD activity with age in the cerebral cortex, attaining adult values by 60 weeks GA and being already at term approximately 45% of the mean adult figure. In the cerebellum, the relative development of pre- and postsynaptic markers was the reverse of that in the cerebral cortex: GAD specific activity had reached the adult value by 60 weeks GA and approximately 40% of this adult level was attained at term, while the muscimol binding site concentration was only about 10% of the adult value at term and was still increasing at 60 weeks GA. The affinity of the receptor for [3H]-muscimol did not change during development, and was the same in cerebral cortex and cerebellum.