Neuroimmune dysfunction induced by prenatal stress exposure

PIVOZ AVEDIKIAN, J.E.; GENARO, A.M.; DI ROSSO, M.E.; ZORRILLA ZUBILETE, M.A.; PASCUÁN, C.G.; WALD, M.R.

Capital Federal

Simposio; First International Symposium of DOHaD and Stress; 2017

Ibero-American Chapter of DOHaD International Society, Sociedad Argentina de Farmacología Experimental

Exposure to early life adversity may deeply affect brain development leading to long-lasting effects on neuronal structure and behavior, playing a key role in the etiology of anxiety and mood disorders. Moreover, PS can result in stable long-term changes in central and peripheral stress response systems as well as influence the response to stress in adulthood. However, there are studies in animals that suggest that PS has an adaptive effect that helps offspring respond appropriately to stressors in the environment. Genetic predisposition, including animal strain, polymorphism and gender, are factors that contribute to vulnerability/resilience against PS. It has been proposed that elevated maternal corticoids levels induce HPA hyperactivity due to a reduced negative feedback by decrease of hippocampal GR-expressing neurons. However, it has been proposed that despite the important role of cortisol in fetal programming, there is much evidence indicating that associations between maternal psychosocial stress and offspring outcome may involve other mechanisms than cortisol physiology. Thus neurotrophins, that play a crucial rol in the formation and plasticity of neuronal networks, have been shown to be involved in the pathophysiology of suicide and depression. In addition, shifts in the Th1/Th2 balance have been involved in the pathogenesis of many human illnesses, such as autoimmune diseases, sleep disturbance, major depression and other disorder.In this context, the purpose of the present study was to analyze the impact of PS exposure on behavior and cognition in adult life as well as the impact of PS on chronic stress situations. In addition, we investigated if these long-lasting effects induced by prenatal stress exposure were related to alterations in stress reactivity and/ or changes in cytokine and/or neurotrophin levels in hippocampus. Furthermore, we analyzed if the molecular changes in hippocampus are also found in lymphocytes in order to propose these cells as peripheral markers of susceptibility to behavioral alterations. For this purpose, pregnant mice were placed in a cylindrical restraint tube for 2 h daily during the last week of pregnancy. Control pregnant females were left undisturbed during their entire pregnancy period. Because several studies have reached a consensus that PS has sex specific adverse effects on behavior, we compared the PS effects in adult males and females in this study.Results indicated that prenatal restraint stress during late gestation induced long-lasting deficits in spatial memory performance in female, but not male, mice. In addition, these alterations was accompanied by an increase in glucocorticoid receptors, a decrease in BDNF expression and a shift to Th2 dominated immune was related to Interestingly, these changes were observed in peripheral lymph nodes as well. These results indicate that lymphoid cells could be good candidates as peripheral markers of susceptibility to behavioral alterations associated with prenatal exposure to stress.