Ulinastatin up-regulates glutamate transporters in glial cells

Abstract

General anesthesia impairs glutamate homeostasis at synapses by decreasing the production of glutamate transporters. Glutamate transporters in astrocytes are important to preserve cognitive function and memory in hippocampus. In this study we investigated whether ulinastatin increases the number of glutamate transporters in glial cells. We used human astrocytes to demonstrate glutamate uptake in glial cells. The cells were divided into control and ulinastatin-treated groups. After incubation for 3 hours in serum free media, ulinastatin was administered to ulinastatin-treated group, then media was changed to HBSS buffer with 0.1 mM of glutamate. And we determined glutamate absorption by astrocytes by measuring glutamate levels in the media and astrocyte lysates at a time. We also measured levels of the glutamate transporters. In the ulinastatin-treated group, the total amount of glutamate was decreased, and the amount in astrocytes was significantly increased, compared to the control group. Expression of glutamate transporter 1 and glutamate aspartate transporter was significantly increased in the ulinastatin group. In this study, administration of ulinastatin resulted in increased glutamate uptake by astrocytes. We also demonstrated glutamate transporters. Thus, we propose that ulinastatin may improve short memory impairment and cognitive disorder after anesthesia by increasing the number of glutamate transporters.