Chronic RU486 treatment reduces age-related alterations of mouse hippocampal function

The present study investigates the protective effect of a chronic blockade of the glucocorticoid receptor (type II) by a single weekly SC injection (20 mg/kg) of RU486 (a potent antiglucocorticoid) from mid-age (12 months old) until senescence (20 to 22 months old) on perturbations of some electrophysiological parameters classically observed in CA1 hippocampal slices of aged BALB/c mice. In this CA1 hippocampal area, no electrophysiological difference was observed at a stimulation frequency of 0.3 Hz. However, an important age-related effect was observed in not-treated animals concerning the three phases of the synaptic response during and after 4 Hz repetitive stimulation ith impairment of the frequency potentiation (FP). Interestingly, this electrophysiological disturbance disappeared completely in aged animals treated previously with RU486. Furthermore, a 10 microM CORT bath application had no effect in CA1 of aged animals, while it produced the classical type II-mediated population spike (PS) decrease in adult animals. This PS amplitude decrease was maintained in aged animals previously treated with RU486. These electrophysiological findings suggest an important type II-mediated glucocorticoid action on age-related alterations of hippocampal function.