Efeito da restrição protéica materna durante a lactação sobre a resposta de timócitos da prole jovem de ratos Wistar

Abstract

In this study, we investigated the consequences of maternal protein deprivation during lactation on thymocyte responses of the offspring Wistar rats (PD group) and the role of leptin in these alterations. Compared to group C, PD animals showed at 30 days of age, lower body and thymus weights, with no alteration in the thymocyte number or any difference in the profile of T cell subsets, or in their proliferative response. Similar circulating levels of corticosterone and GR nuclear contents were detected in thymic cells of PD or control groups. In contrast, despite the rats from PD group did not present alterations in leptin circulating levels, the expression of leptin receptor ObRb was enhanced in their thymocytes. This change was accompanied by an amplification in leptin signaling response of thymocytes from PD rats, which showed an increase in JAK2 and STAT3 phosphorylation after stimulation with leptin. Moreover, the thymic cells from PD rats presented a decreased rate of spontaneous apoptosis when compared to controls. Accordingly, higher expression of both the anti-apoptotic protein Bcl-2 and Procaspase-3 and lower expression of pro-apoptotic protein Bax were detected in PD thymocytes, however, the pro-apoptotic protein bad expression was similar between the groups. Thymocytes from PD group also exhibited a constitutive higher nuclear content of p65 NFkB associated to a lower IkB content in the cytoplasm. Finally, although there was no change in db genic (leptin receptor) expression in PD thymocytes, a higher expression of mRNA for ob gene (leptin) was observed in the thymic microenvironment from PD animals. Taken together, the results show that maternal protein deprivation during lactation affects thymic homeostasis, inducing leptin activity, which protect thymocytes from apoptosis in young progeny and, perhaps,may prone these animals for alterations in immune response in adult life.