Abstract
The glial glutamate transporter GLT-1 has a crucial role in preventing the glutamate-excitotoxic processes. Neurosteroid dehydroepiandrosterone (DHEA) is also supposed to exert a potential neuroprotective effect against the glutamate-exitotoxicity, however, the relationship between GLT-1 and DHEA is unknown. Using a real-time optical recording technique, the present study aimed to examine the effects of DHEA on the activity of GLT-1 in the rat hippocampal dentate gurus slices stained with the voltage-sensitive dye RH155. We found that an application of DHEA to the slices increased rapidly and dose-dependently the synaptically induced glial depolarization (SIGD), an indicative of GLT-1 activity. As DHEA had little effect on presynaptic glutamate releases, the DHEA-induced SIGD increase should not be a secondary effect of DHEA on the glutamate releasing machinery. The DHEA-increased SIGD was largely reduced by the inhibitors for sigma-1 receptor and protein kinase C, but not by those for Dopamine-1receptor and protein kinase A, suggesting that DHEA prevents the glutamate-excitotoxicity by a sigma-1 receptor/PKC-mediated up-regulation of GLT-1 activity. [J Physiol Sci. 2007;57 Suppl:S84]
