Avaliação neuroendócrina, metabólica e psicobiológica em prole de ratas Wistar suplementadas com selenito de sódio durante o período de prenhez e lactação

Abstract

Selenium (Se) is an important element in the regulation of fetal and neonatal development. Thus, the objective of this study was to evaluate the possible occurrence of neuroendocrine, metabolic and behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite at dose of 1mg/kg, by orogastric route. For this purpose, initially, was checked thyroid function of offspring soon after the end of treatment. Then, in order to investigate the Se influence on the metabolic programming of animals, it was assessed milk intake and the body weight monitoring since the neonatal period to adulthood. Furthermore, we investigated the repercussions on energy homeostasis through the assessment of lipid metabolism and glucose tolerance test after the treatment, as well as by measurements of basal and fasting glucose in the adult phase. Regarding the motivated behavior, protocols were performed to assess the water and food intake, in basal conditions and underfasting. Moreover, to determine the Se supplementation effects in the ontogeny of central nervous system, it was performed the indirect neurochemical evaluation by cholinesterase activity in different brain regions and by the hippocampal expression of tryptophan hydroxylase (TPH2) and tyrosine hydroxylase (TH). Finally, the open field test, the elevated plus maze test, forced swimming test and the object recognition task were used to determine the cognitive abilities and behavioral profile of individuals in adulthood. According to the results, it was demonstrated that supplementation with sodium selenite causes increased levels of thyroxine (15%) and triiodothyronine (25%), while increasing the expression of type 2 deiodinase in brown adipose tissue (351%). Thus, the increased bioavailability of thyroid hormones causes changes in energy homeostasis characterized by higher consumption of neonatal milk (275%), greater mobilization of triglycerides in the liver (23%) and adipose tissue (24%) and more effective reestablishment of glicemia after oral glucose tolerance test (24%). Indeed, the change in ingestive behavior are perpetuated into adulthood, highlighting the increased food intake in basal conditions (19%). Furthermore, Se treatment promotes reduction of cholinesterase activity (33%) and lower TPH2 expression (12%), but increases the levels of mRNA for TH (200%) in the hippocampus. Therefore, we believe that these neurochemical changes are strongly related to the behavioral profile in adulthood. Based on this premise, it was found that the offspring of females supplemented with Se have higher locomotor activity (50%) and more rearing (77%) in the open field test. Also, There was an apparent anxiolytic activity expressed by higher time spent in the open arms (143%) in the test of elevated plus-maze. Finally, through the object recognition task, it was proven that the programmed offspring shows greater cognitive capacity, reflected in a higher absolute (230%) and relative (14%) index discrimination. In summary, the results demonstrate that maternal supplementation with sodium selenite affects the ontogeny of physiological systems involved in the neuroendocrine and metabolic homeostasis, as well as the differential expression of emotional and motivational behaviors.