SELECTIVE REDUCTION OF GLUCOCORTICOID RECEPTOR IMMUNOREACTIVITY IN THE HIPPOCAMPAL-FORMATION AND CENTRAL AMYGDALOID NUCLEUS OF THE AGED RAT

Hippocampal cell loss during aging has been related to the toxic effects of corticosterone on this cell population. It is not known which receptor mediates corticosterone cytotoxicity. At least two types of receptors for corticosterone have been recognized in the rat brain, type I (corticosterone preferring receptor, CR) and type II (glucocorticoid receptor, GR). In the present study the possible changes in GR immunoreactivity (IR) in various tel- and diencephalic regions of the aged rat have been investigated using immunocytochemistry coupled with computer-assisted image analysis. Male Sprague-Dawley rats of 3, 12 and 24 months of age were used (n =5/group). A selective decrease of GR-IR was observed in the CA1 hippocampal field and central amygdaloid nucleus of the 24-month-old with respect to both 3- and 12-month-old rats. While in the former region GR-IR decrease was paralleled by a decrease of IR field area, no age-related decrease of GR-IR profile number was detected in central amygdaloid nucleus. A significant decrease of GR-IR and IR field area was also observed in the dentate gyrus of 24- vs 12-month-old rats but not vs 3-month-old rats. The analysis of adjacent sections stained with Cresyl violet showed a pattern of age-related changes (decrease of neuronal profiles in CA1 field pyramidal layer and dentate gyrus granular layer, and no change in the central amygdaloid nucleus of age rats) which paralleled the observed changes in GR-IR in the same areas. This study provides evidence that GR are selectively decreased in the hippocampal formation and in the central amygdaloid nucleus of the aged rat. However, only in the aged hippocampal formation GR decrease seems to be due to a loss of GR-containing neurons. The absence of age-related changes in the number of GR target neurons in all the other areas analyzed (even neurons which contain high levels of GR) suggests that the activation of CR, which are selectively concentrated in the hippocampal formation, or possibly the combined activation of CR and GR, may be responsible for corticosterone cytotoxicity.