Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments

The temporal pattern of exposure to glucocorticoids has been reported to be a critical factor in determining the outcome of glucocorticoid actions at the brain. In this work, the effects of different regimes of subcutaneous corticosterone administration (acute-single injection-vs. chronic-daily injection for 21 days) on the expression of the neural cell adhesion molecule (NCAM) were evaluated in different rat brain regions (CA1-CA4, dentate gyrus, frontal cortex, striatum, and hypothalamus). The treatments were selected according to previous studies in which we showed biphasic effects of corticosterone on memory formation, with acute corticosterone effects being facilitating and chronic effects being deleterious. In addition, the chronic treatment was shown by others to result in structural alterations at the hippocampus. NCAM was evaluated given its cell-cell recognition and adhesion properties, and the involvement on synaptic stabilisation subserving long-term memory formation. The results showed a biphasic modulation of NCAM levels at the frontal cortex, with acute corticosterone resulting in enhanced NCAM levels at 8 h and 24 h posttraining, and the chronic treatment decreasing its expression. None of the other brain areas examined showed significant changes in NCAM expression with corticosterone treatments, except for the hypothalamus that showed reduced NCAM levels after the chronic corticosterone regime. These results support the view that NCAM regulation at the frontal cortex might be a mechanism by which corticosterone treatments influence memory formation. They also highlight the hypothalamus as a brain area particularly sensitive to NCAM regulation by prolonged exposure to elevated glucocorticoids.