Developmentally retarded expression of the glial glutamate transporter, GLT-1, in the cerebral cortex of senescence-accelerated prone mouse SAMP8

Abstract Here, we studied the involvement of glutamate accumulation in the synaptic cleft in the distinctive defects in the brain of SAMP8. First, we demonstrated the developmental changes in glutamate transporter activities in the cerebral cortex of SAMP8 and SAMR1 at ages 4, 10, 16 and 32 weeks. Glutamate transporter activity in SAMR1 reached a maximum at 10 weeks of age. Thereafter, there was no significant change observed up to at least 32 weeks of age. Although the same activities were observed in two strains at ages of 4 and 32 weeks, the activities in 10- to 16-week-old SAMP8 were markedly lowered in comparison with those in age-matched SAMR1. Next, we showed the developmental changes in glutamate transporter proteins, a neuronal EAAC1 and two glial GLT-1 and GLAST, by immunoblotting analysis in the cerebral cortex of SAMP8 and SAMR1 at the above indicated ages. In the two strains, developmental changes in the content of GLT-1 protein were extremely similar to those in glutamate transporter activities. Additionally, the concentration of EAAC1 protein in the two strains showed a slight similarity to the developmental change in transporter activity, while there was no difference between the two in the expression of GLAST protein. These results suggest that the reduction of glutamate transporter activity in 10- to 16-week-old SAMP8 compared with that in age-matched SAMR1 is mainly caused by the developmentally retarded expression of GLT-1 protein.