Ischemia induced changes in expression of the astrocyte glutamate transporter GLT1 in hippocampus of the rat

Changes in cellular uptake of glutamate following transient cerebral ischem ia is of possible importance to ischemia induced cell death. In the present study, we employed in situ hybridization and immunohistochemistry to inves tigate the influence of cerebral ischemia on expression of mRNA and protein of the astrocyte glutamate transporter GLT1, and of glial fibrillary acidi c protein. Different subfields of CA1 and CA3 of the rat hippocampus were s tudied at various time-points after ischemia (days 1, 2, 4, and 21). In CA1 , GLT1-mRNA was decreased at all time-points after ischemia except from day 2, whereas in CA3, decreases were seen only on day I. Expression of GLT1-p rotein in CA1 was unchanged during the initial days after ischemia, but dec reased markedly from day 2 to if. In CA3, GLT1-protein increased progressiv ely throughout the observation period after ischemia. Following the degener ation of CA1 pyramidal cells, a positive correlation between the number of CA1 pyramidal cells and expression of either GLT1-mRNA or -protein was evid ent selectively in CA1. Increases in expression of mRNA and protein of glia l fibrillary acidic protein were present from day 2, most notable in CA1. T he present data provide evidence that expression of GLT1 in CA1 of the hipp ocampus is not decreased persistently before the degeneration of CA1 pyrami dal cells, but is downregulated in response to loss of these neurons. Since the reduction in GLT1 expression evolved concomitantly with the degenerati on of CA1 pyramidal cells, it may contribute to the severity of CAI pyramid al cell loss. A progressive postischemic increase in GLT1 expression in CA3 may be linked to the resistance of CA3 neurons to ischemic cell damage. (C ) 2000 Elsevier Science Ltd. All rights reserved.