The relationship between the susceptibility to convulsions, the content of
pyridoxal 5'-phosphate and the activity of
pyridoxal kinase (EC 2.7.1.35) and
glutamate decarboxylase (EC 4.1.1.15) in brain, was studied in the developing mouse.
Seizures were induced by
pyridoxal phosphate-gamma-glutamyl hydrazone (
PLPGH), a
drug previously reported to reduce the levels of
pyridoxal 5'-phosphate and as a consequence to inhibit the activity of
glutamate decarboxylase in brain of adult mice. It was found that the seizure pattern, as well as the time of appearance of convulsions, differed between 2- and 5-day old mice and 10-day old or older mice, indicating a progressive increase in seizure susceptibility during development. In brain,
pyridoxal kinase activity and
pyridoxal 5'-phosphate levels were decreased by the administration of
PLPGH at all ages studied, whereas
glutamate decarboxylase activity was inhibited less than 25% in 2- and 5-day old mice, and about 50% thereafter. Parallelly, the activation of
glutamate decarboxylase by
pyridoxal 5'-phosphate added in vitro to control homogenates was less in 2- and 5-day old mice than in older animals. It is concluded that the increase in the susceptibility to
seizures induced by
PLPGH during development is probably related to the increase observed in the sensitivity of
glutamate decarboxylase in vivo to a decrease of
pyridoxal 5'-phosphate levels. The correlation between
pyridoxal 5'-phosphate,
glutamate decarboxylase, and seizure susceptibility seems to be established at about 10 days of age.