Evaluating the interaction between early postnatal inflammation and maternal care in the programming of adult anxiety and depression-related behaviors

The perinatal development of the nervous system is influenced by different external and internal stimuli. Previous data show that maternal care and perinatal inflammation can induce long-term changes in anxiety- and depression-related behavior. Our hypothesis is that both maternal care and perinatal inflammation act through interacting biological pathways to program adult behavior. To evaluate this interaction, we combined a protocol of maternal care variation in mice (C57BL/6J × BALB/c reciprocal F1 offspring) with the administration of bacterial wall lipopolysaccharide (LPS) at a previously reported sensitive development age (postnatal day 3, P3). The analysis of maternal behavior revealed that pups from C57BL/6J dams received more maternal attention than those taken care by BALB/c dams. Pups receiving LPS at P3 showed an acute corticosterone response, and a dose-dependent desensitization of this hormonal response when challenged with LPS at adulthood. We analyzed adult behavior on 6 highly validated tests and found an interaction between maternal care and early postnatal LPS on 7 anxiety-related behaviors in 4 different tests. In particular, early postnatal LPS treatment resulted in higher anxiety-related behavior when administered to females receiving more maternal care (C57 pedigree), but reduced depression-related behavior in males of the same pedigree. These results suggest that specific coping strategies are sensitive to maternal care and/or postnatal inflammation programming of adult anxiety- and depression-related behaviors, suggesting that both divergent and convergent mechanisms participate in this programming.