Developmental changes of .GAMMA.-aminobutyric acid (GABA) and putative amino acid neurotransmitters in the organotypic culture of newborn mouse cerebellum.

The quantitative changes and metabolism of GABA and putative amino acid neurotransmitters during early developmental stages in the organotypic culture of newborn mouse cerebellum were examined by using the high-performance liquid chromatograph (HPLC) technique. D-[U-¹⁴C]Glucose was used as a precursor of amino acids.<br> To analyze amino acid neurotransmitters, explants were incubated for 4 weeks under standard conditions. The amount of GABA linearly increased from 8.7±1.3nmol/mg protein (2days in vitro, 2 DIV) to 26.5±6.1nmol/mg protein (15 DIV) and was saturated after that (24.0±3.6nmol/mg protein at 30 DIV). During the period of GABA increase, the capability for GABA synthesis from [¹⁴C]glucose increased rapidly from 3.03±0.67nCi/mg protein (2 DIV, 3h incubation) to 9.32±1.34nCi/mg protein (15 DIV, 3h incubation).<br> In the case of glutamic acid, a putative neurotransmitter of granule cell parallel fibers in the cerebellum, the amount in explants was nearly constant during incubation, in contrast with the fact that the amount in vivo gradually increased. However, the capability for glutamic acid synthesis from [¹⁴C]glucose increased from 10.80±3.01nCi/mg protein (2 DIV, 1h incubation) to 27.62±4.71nCi/mg protein (22 DIV, 1h incubation). In the case of taurine, found in abundance in fetal brain and supposed to play a specific role in the development and maturation of the central nervous system, the amount in explants decreased from 139.8±4.0nmol/mg protein (2 DIV) to 54.0±0.8nmol/mg protein (30 DIV). The pattern of change of taurine was similar to that observed in vivo.<br> On considering together the results obtained in this report and the previous one (Satomi, D. (1983) J. Biochem. 94, 785-791), it was presumed that in the organotypic culture of newborn mouse cerebellum, biochemical changes of neurotransmitters are closely related to morphological development in nearly the same manner as in vivo.