Persistently High Corticosterone Levels but Not Normal Circadian Fluctuations of the Hormone Affect Cell Proliferation in the Adult Rat Dentate Gyrus

Abstract

The dentate gyrus is one of the few brain structures where new neurons are added throughout adulthood in several mammalian species, including humans. Production of new neurons can be regulated by factors which influence cell proliferation or newborn cell survival. Supplementation or deprivation of glucocorticoids, adrenal hormones involved in the response to stress, affect cell proliferation, leading to a decrease or an increase, respectively, in the number of newborn cells. Glucocorticoid secretion under physiological conditions follows a circadian pattern. We thus investigated a possible relationship between cell proliferation and circadian oscillations of corticosterone secretion in the adult rat dentate gyrus. Corticosterone is the species-specific glucocorticoid hormone of the rat. 5-Bromo-2′-deoxyuridine was used to evaluate cell proliferation at 4 different time points in the light-dark cycle. No correlation was found between corticosterone circadian oscillations and cell proliferation in the adult dentate gyrus. In contrast, constantly high corticosterone levels, obtained by implanting corticosterone pellets, decreased cell proliferation in particular zones of the dentate gyrus, i.e. the hilus and the superior blade of the granule cell layer. These findings show that a short, physiologically occurring exposure to high corticosterone levels does not influence cell proliferation, whereas a lengthy exposure to this hormone does induce anatomically localized proliferative changes.