RESUMEN
Animal models are crucial to understanding the mechanisms underlying the deleterious consequences of early-life stress. Here, we aimed to examine the effect of the limited bedding nesting (LBN) paradigm on early life development milestones and anxiety- and/or depression-like behavior in adolescent and adult mice from two inbred mice of both sexes. C57BL/6NCrl and BALB/c litters were exposed to the LBN paradigm postnatal day (PND) 2-9. Maternal behavior recording occurred on PND 3-9, and pups were weighed daily and examined to verify the eye-opening on PND 10-22. The male and female offspring underwent evaluation in the open field test, elevated plus-maze, and the forced swimming test during adolescence (PND 45-49) and adulthood (PND 75-79). We found that LBN impaired the maternal behavior patterns of both strain dams, mainly on C57BL/6NCrl strain. Also, LBN delayed the pup's eye-opening time and reduced body weight gain, impacting C57BL/6NCrl pups more. We also found that LBN decreased anxiety-related indices in adolescent and adult male but not female mice of both strains. Furthermore, LBN decreased depression-related indices only adolescent female and male BALB/c and female but not male C57BL/6NCrl mice. These findings reinforce the evidence that the LBN paradigm impairs the maternal behavior pattern and pup's early developmental milestones but does not induce anxiety- or depressive-like behavior outcomes during later life.
Asunto(s)
Trastornos de Ansiedad , Ansiedad , Masculino , Humanos , Femenino , Animales , Ratones , Ratones Endogámicos C57BL , Conducta Materna , Ropa de Cama y Ropa Blanca , Conducta AnimalRESUMEN
Background: Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas' disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On this way, in this article we analyzed the host genetic influence on hematological, histopathological and immunological aspects after T. cruzi infection. Methods: BALB/c and A mice were intragastrically infected with T. cruzi SC2005 strain, isolated from a patient of an outbreak of Chagas disease. Parameters such as parasite load, survival rates, cytokines production, macrophages, T and B cell frequencies, and histopathology analysis were carried out. Results: BALB/c mice presented higher parasitemia and mortality rates than A mice. Both mouse lineages exhibited hematological alterations suggestive of microcytic hypochromic anemia and histopathological alterations in stomach, heart and liver. The increase of CD8+ T cells, in heart, liver and blood, and the increase of CD19+ B cells, in liver, associated with a high level of proinflammatory cytokines (IL-6, TNF-α, IFN-γ), confer a resistance profile to the host. Although BALB/c animals exhibited the same findings observed in A mice, the response to infection occurred later, after a considerable parasitemia increase. By developing an early response to the infection, A mice were found to be less susceptible to T. cruzi SC2005 infection. Conclusions: Host genetics background shaping the response to infection. The early development of a cytotoxic cellular response profile with the production of proinflammatory cytokines is important to lead a less severe manifestation of Chagas disease.