Alteraciones de conducta y respuesta neuroinmune en células microgliales en ratas hembra adultas expuestas neonatalmente a un doble reto estrés – inmune

Abstract

Maternal separation and exposure to early-stage infections are stressors that predispose the individual to behavioral disturbances, such as anxiety and depression. However, little is known about how stress induced by two factors such as maternal separation and the simulator of an infection, through lipopolysaccharides (LPS), can alter normal brain development during early life and induce greater vulnerability to psychopathologies. In humans an important predictor of an individual's susceptibility is their sex, women show higher rates of anxiety and depression. We analyzed whether adult female rats exposed to a double stress-immune challenge in the neonatal stage show alterations in anxious and depressive behaviors, as well as in the neuroimmune response of microglial cells in the Hilus and CA3 areas of the hippocampus. Four groups of adult female Sprague Dawley rats were used: a control group consisting of undisturbed pups (CONT-VEH), a group subjected to maternal separation (SM, 3 h / day, 1-14 days postnatal), a group in which Lipopolysaccharide (LPS, 0.5 mg / kg) was injected on postnatal day (PN) 14 and a group subjected to the double SM-LPS challenge. All groups were weaned on postnatal day 21 and remained in the animal house until conducting behavioral tests. At 5 months of age, the rats were subjected to the open field tests (OFT), elevated plus maze (EPM) and forced swim (FST). After the behavioral tests, the rats were sacrificed and the brains were collected for further treatment. Finally, immunohistochemistry was performed with the anti-Iba1 antibody, specific for microglia.

Maternal separation and exposure to early-stage infections are stressors that predispose the individual to behavioral disturbances, such as anxiety and depression. However, little is known about how stress induced by two factors such as maternal separation and the simulator of an infection, through lipopolysaccharides (LPS), can alter normal brain development during early life and induce greater vulnerability to psychopathologies. In humans an important predictor of an individual's susceptibility is their sex, women show higher rates of anxiety and depression. We analyzed whether adult female rats exposed to a double stress-immune challenge in the neonatal stage show alterations in anxious and depressive behaviors, as well as in the neuroimmune response of microglial cells in the Hilus and CA3 areas of the hippocampus. Four groups of adult female Sprague Dawley rats were used: a control group consisting of undisturbed pups (CONT-VEH), a group subjected to maternal separation (SM, 3 h / day, 1-14 days postnatal), a group in which Lipopolysaccharide (LPS, 0.5 mg / kg) was injected on postnatal day (PN) 14 and a group subjected to the double SM-LPS challenge. All groups were weaned on postnatal day 21 and remained in the animal house until conducting behavioral tests. At 5 months of age, the rats were subjected to the open field tests (OFT), elevated plus maze (EPM) and forced swim (FST). After the behavioral tests, the rats were sacrificed and the brains were collected for further treatment. Finally, immunohistochemistry was performed with the anti-Iba1 antibody, specific for microglia.