Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta

Abstract

According to the World Health Organization (2010), stress is recognized and identified as the evil of the century due to its chronicity and repercussions that are directly connected to life quality, family and society. Pre-natal animal models of stress and neonatal isolation reproduce many characteristics of chronic stress or adverse experiences lived in the beginning of life. Therefore, this study aimed to investigate if stress during the fetal and neonatal period could modify biochemical, morphologic and molecular parameters in adult offspring. In the first experiment (EXP1), pregnant Wistar rats were subjected to prenatal stress for two weeks while the pregnant rats in the second experiment (EXP 2) were not handled until their pups‟ birth, which were exposed to a neonatal isolation protocol. Biochemical, morphological and molecular analyzes were performed on postnatal day 50 of both experiments. In EXP1, animals exposed to maternal stress showed increased oxidative stress, persistent histological changes, as well as neurotrophin changes related to cell plasticity. Inversely, animals exposed to neonatal management (EXP2) showed better memory performance, which was accompanied by increased neurogenesis observed by increased neurotrophins involved in neuroplasticity, as well as in histological analysis. Considering the strong emotional stress involvement with increased corticosterone levels, we also decided to investigate some molecular markers related to HPA axis stimulation through glucocorticoid receptor dosage whose immunoreactivity was reduced in the EXP1 group at the same time that increased in the EXP2. As stress exposure has been related to drug addiction, in both experimental protocols a group of animals was exposed to morphine with consequent evaluation of mu opioid receptor density. As a result, EXP1 animals showed increased of mu opioid receptor immunoreactivity after morphine exposure while animals from EXP2 showed increased immunoreactivity, which was also observed in animals not exposed to morphine, indicating a change per se due to postnatal handling. The results presented indicate that stressful experiences during the prenatal period may develop persistent deleterious changes throughout life. On the other hand, neuroadaptive changes resulting from neonatal isolation showed an ability to overcome stress showing an increase in persistence resilience during their development until adulthood.