Avaliação dos efeitos do exercício físico antes do período gestacional sobre as alterações do eixo hipotálamo-pituitária-adrenal em camundongos adultos estressados no período pré-natal

Abstract

INTRODUCTION: Potential threats to homeostasis may occur during the in utero period, promoting programming effects on both neurological development and hypothalamic-pituitary-adrenal (HPA) axis function. The HPA axis acts as a control and regulatory center of the body that connects the central nervous system to the hormonal system. The axis responds to the stressor stimulus and assists the body to maintain homeostasis, as well as being essential to the normal regulatory physiological functioning. Physically fit and physically active individuals exhibit a lower rate of health problems, especially when faced with stressful situations, contributing to reduced levels of anxiety and depression. OBJECTIVE: To evaluate the effects of physical exercise before the gestational period on changes due to prenatal stress in adult mice. METHODS: Balb/c female and male mice were divided into three groups: control (CTLE), prenatal restraint stress (PNS) and physical exercise before the gestational period and prenatal restraint stress (EX+PNS). The weight of the animals was evaluated during gestation, days 1, 10 and 21 of life and also as adults. Animals were then maintained until adulthood (60 days of life) when fear/anxiety behaviors were evaluated in the elevated plus maze, and depression was evaluated using the preference for sucrose and the ingestion of sucrose test. In addition, real-time PCR gene expression of corticotrophin releasing hormone (CRHR1) type 1 receptor in the prefrontal cortex, glucocorticoid receptor (GR) and mineralocorticoid (MR) receptor in the hippocampus, as well as plasmatic concentrations of corticosterone were evaluated. RESULTS: During gestation, females of the EX+PNS group presented greater weight in relation to the CTLE group. Regarding the offspring weight, animals of the EX+PNS group showed an increase in weight on days 1, 10 and 21 of life, compared to the PNS group. During the adult life, animals stressed in the prenatal period presented lower weight, while the pregestational exercise promoted an increase in the offspring weight in relation to the CTLE group. In relation to behavioral tests, there was a significant decrease in the time spent in the open arms of the elevated plus maze in the PNS and EX+PNS groups, in both sexes, demonstrating an increase in fear/anxiety behavior. Prenatal stress increased the preference for sucrose in females and sucrose intake in both sexes. However, exercise promoted a significant decrease in sucrose intake in males and females. CRHR1 expression decreased in the prefrontal cortex of EX+PNS females compared to the PNS group. On the other hand, pregestational exercise was not able to reverse the significant decrease in basal GR concentrations caused by prenatal stress in adult females. There were no significant differences between groups in GR gene expression in males, as well as in MR and corticosterone in both females and males. CONCLUSION: Physical exercise on the treadmill before the gestational period seems to be able to reduce the effects of prenatal stress on important markers of the HPA axis response in a sex-dependent manner.