DOWN-REGULATION OF GLIAL GLUTAMATE TRANSPORTERS AFTER GLUTAMATERGIC DENERVATION IN THE RAT-BRAIN

Membrane-localized transporter proteins, expressed in both neurons and glial cells, are responsible for removal of extracellular glutamate i n the mammalian CNS. The amounts and activities of these transporters may be under regulatory control. We demonstrate here that cortical les ions, which decrease striatal glutamate uptake in synaptosome-containi ng homogenates by similar to 50%, also decrease the striatal concentra tions of the astrocytic glutamate transporter proteins, GLT-1 and GLAS T by similar to 20-30%. Since GABA uptake activity was not decreased a nd glial fibrillary acidic protein was increased in the same samples, the lesion-induced losses of GLT-1 and GLAST were not caused by a gene ral impairment of neuronal or glial function. The observed reduction i n the two astrocytic glutamate transporters after corticostriatal nerv e terminal degeneration indicates that their levels of expression are dependent on glutamatergic innervation.