Chronic corticosterone manipulations in mice affect brain cell proliferation rates, but only partly affect BDNF protein levels

We investigated whether the effects of corticosterone (CORT) on brain cell proliferation are mediated via its detrimental effect on brain-derived neurotrophic factor (BDNF). Using a [H-3]thymidine tracer study, it was demonstrated that the cell proliferation rate in the neurogenic hippocampus and subventricular zone was increased in placebo-treated adrenalectomized (ADX) mice with low plasma corticosterone levels when compared with chronically CORT-treated ADX animals (25 mg or 100 mg sustained-release pellet). The cell proliferation rate of SHAM animals was in between the ADX-placebo group and ADX CORT-treated groups. BDNF protein contents in the hippocampus and subventricular zone were not different between the SHAM group and ADX-placebo group, although BDNF contents were decreased in the chronically CORT-treated ADX animals. Thus, other factors besides BDNF are involved in mediating CORT-induced changes in cell proliferation. Further, CORT manipulations did not affect caspase-3-like activity in any of the brain regions investigated, suggesting that caspase-3 is not involved in possible CORT-induced cellular losses.