Relationships between GABA and polyamines in developing rat brain

Abstract

The levels of GABA were increased in brains of rats during postnatal development by treatment with 4-aminohex-5-enoic acid, a specific enzyme-activated inhibitor of GABA aminotransferase. The rate of GABA increase followed the developmental increase of glutamate decarboxylase. However, there was a very substantial net increase of brain GABA levels even at day 3, and the net increase of brain GABA at day 10 was as great as in the mature brain. Elevation of brain GABA in 25-day old rats was accompanied by a 50% decrease of S-adenosylmethionine decarboxylase activity. Sixteen hours after administration of the GABA aminotransferase inhibitor a severalfold increase of ornithine decarboxylase activity and of putrescine concentration was observed. Despite the marked increase in brain GABA levels, changes of the polyamine biosynthetic enzymes and of putrescine could not be detected in the immature brains. Bicuculline did not modify the effects of treatment with the GABA aminotransferase inhibitor, and muscimol had no effect on GABA levels or on polyamine biosynthesis. Glia formation in rat brain is most active between days 10 and 22 of postnatal life. Nerve endings contain the major proportion of GABA and glutamate decarboxylase but they do not contain significant ornithine decarboxylase activity. When brain GABA levels are increased by inhibition of its degradation, not only the synaptosomal, but also the non-synaptosomal GABA increases considerably. Taking these and all other known facts together, it is evident that the observed changes in the polyamine biosynthetic enzymes occur preferentially in the glial compartment of the brain.