Glutamate transporter expression in astrocytes of the rat dentate gyrus following lesion of the entorhinal cortex

The glutamate transporters GLT-1 and GLAST localized in astrocytes are esse ntial in limiting transmitter signalling and restricting harmful receptor o verstimulation. To show changes in the expression of both transporters foll owing lesion of the entorhinal cortex (and degeneration of the glutamatergi c tractus perforans), quantitative microscopic in situ hybridization (ISH) using alkaline-phosphatase-labelled oligonucleotide probes was applied to t he outer molecular layer of the hippocampal dentate gyrus of rats (terminat ion field of the tractus perforans). Four groups of rats were studied: sham -operated controls, and animals 3, 14 and 60 days following unilateral elec trolytic lesion of the entorhinal cortex. The postlesional shrinkage of the terminal field of the perforant path, ipsilateral to the lesion side, was determined and considered in the evaluation of quantitative ISH data. Stati stical analysis revealed that ipsilateral to the lesion side there was a si gnificant decrease of the GLT-1 mRNA at every postlesional time-point and o f the GLAST mRNA at 14 and 60 days postlesion. The maximal decrease was app roximate to 45% for GLT-1 and approximate to 35% for GLAST. In the terminal field of the perforant path contralateral to the lesion side, no significa nt changes of ISH labelling were measured. The results were complemented by immunocytochemical data achieved using antibodies against synthetic GLT-1 and GLAST peptides. In accordance with ISH results, there was an obvious de crease of GLT-1 and GLAST immunostaining in the terminal field of the perfo rant path ipsilateral to the lesion side. From these data we conclude that, following a lesioning of the entorhinal cortex, the loss of glutamatergic synapses in the terminal field of the perforant path resulted in a strong d ownregulation of glutamate transporters in astrocytes. The decrease of syna ptically released glutamate or of other neuronal factors could be involved in this downregulation.