Pro-apoptotic cell signaling in the prefrontal cortex contributes to depressive-/anxiogenic-like behavioral phenotype of mice subchronically exposed to dexamethasone

Abstract Animal models have been used to investigate the depressive-/anxiogenic-like phenotype induced by synthetic glucocorticoids (GCs). The aim of the present study was to evaluate if apoptosis in the mouse prefrontal cortex (PFC) contributes to the depressive-/anxiogenic-like behavioral phenotype induced by dexamethasone (DEX) subchronic exposure. In the present study, adult male Swiss mice were exposed to DEX (2 mg/kg), or to saline solution (10 ml/kg), by the intraperitoneal route for 21 days. At the 22nd day, the mice performed anxiety- and depressive-like behavior tests. Subsequently, the samples of PFC were designated to the Western blot and Fluoro-Jade C staining analyses. The mice exposed to DEX exhibited a depressive-/anxiogenic-like phenotype, normal locomotor activity profile and a reduction in the weight of adrenal glands (% body weight). Reduced levels of GC receptors and an increase in the FJC-positive cells were found in the PFCs of mice subcronically exposed to DEX. The levels of pro-apoptotic protein cleaved caspase-3 and the ratios of PARP cleaved/total and Bax/Bcl-2 were increased in the PFCs of mice after subchronic exposure to DEX. These findings demonstrate that the pro-apoptotic cell signaling in the PFC contributed to the depressive-/anxiogenic-like phenotype in mice subchronically exposed to DEX.