Selective resistance of taurine-fed mice to isoniazide-potentiated seizures: In vivo functional test for the activity of glutamic acid decarboxylase

Abstract

Taurine, 2-aminoethanesulfonic acid, is one of the most abundant free amino acids especially in excitable tissues, with wide physiological actions. We have previously reported that in mice, supplementation of the drinking water with taurine induces alterations in the inhibitory GABAergic system. In taurine-fed mice we found that the expression level of glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis, is elevated. Increased expression of GAD was accompanied by increased levels of GABA. Here, we investigated pharmacologically the functional significance of taurine-induced increase in GAD expression by determining the threshold for kainic acid–induced seizures after partial inhibition of GAD activity with isoniazide. We found that taurine-fed mice have elevated GAD expression and showed a higher threshold for seizure onset when compared with age-matched controls. Thus, taurine-fed mice have a functional increase in GAD activity which offers some protection in this seizure model. Furthermore, this pharmacological manipulation can be used to determine the level of GAD activity in other model systems that show alterations in GAD expression.