Up-regulated GLT-1 resists glutamate toxicity and attenuates glutamate-induced calcium loading in cultured neurocytes.

Glutamate transporter-1 (GLT-1) plays a dual role in glutamate transportation: both normally devotion to the clearance of glutamate and during some pathological conditions extruding glutamate to the extracellular space. Therefore, it is uncertain whether increased expression of GLT-1 will actually be helpful against glutamate excitotoxicity. In this study, GLT-1 up-regulation was induced by ceftriaxone, and L-glutamate was added to induce glutamate toxicity in primary cultured rat cortical cells. The results showed that up-regulated GLT-1 induced by 1 μM ceftriaxone for 2 days markedly increased cell viability, decreased apoptotic cell death and alleviated ultrastructural damage induced by 50 μM glutamate 15 min. as well as promoted L-[(3) H]-glutamate uptake in cultured cells. GLT-1 up-regulation had no effect on the intracellular free calcium concentration ([Ca(2+) ](i) ) in the resting situation, while relieved intracellular calcium overloading by reducing the elevation and promoting the recovery of [Ca(2+) ](i) following stimulation of 50 μM glutamate for 2 min. Applying 100 μM dihydrokainic acid (GLT-1 antagonist) 30 sec. before glutamate eliminated the above effect of GLT-1 up-regulation on [Ca(2+) ](i) . In conclusion, GLT-1 up-regulation induced by ceftriaxone plays a positive glutamate transporting role against glutamate toxicity in primary cultured rat cortical cells.