Guanidinoacetate Inhibits Glutamate Uptake in Rat Striatum of Rats at Different Ages

Glutamate plays a central role in the excitatory synaptic transmission and is important for brain development and functioning. Increased glutamate levels in the synaptic cleft are related to neuronal damage associated with excitotoxicity. Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA) and depletion of creatine. Affected patients present epilepsy and mental retardation whose pathogeny is unclear. In the present study we investigated the in vitro and in vivo (intrastriatal administration) effect of GAA on glutamate uptake by striatum slices of developing and adult rats. Results showed that GAA significantly inhibited in vitro glutamate uptake at 50 μM and 100 μM in all ages tested. We also tested the effect of taurine on the inhibition of glutamate uptake caused by GAA. Taurine significantly attenuated the inhibitory effect caused by 50 μM GAA, but did not alter that provoked by 100 μM GAA. Furthermore, intrastriatal administration of a solution of 30 μM GAA (0.06 nmol/striatum) significantly inhibited glutamate uptake by rat striatum slices. Our results suggest that the inhibition of striatal glutamate uptake caused by GAA might be involved in the neuropathology and especially in the acute neurological features present in patients with GAMT-deficiency.