Early-life adversity impairs neuronal plasticity of the developing brain. In rodents, brain maturation processes, including neuro- and synaptogenesis, myelination, microglial maturation, and hypothalamic–pituitary–adrenal (HPA) axis development continue in the postnatal period. In our study, two models of early-life stress were used: repeated maternal separation (MS) from postnatal day (PND) 2 to PND14 for 3 h daily and single maternal deprivation (MD) on PND9 for 24 h. Effects of each type of early-life stress on neuron density, neurogenesis, microglial morphology, and HPA axis programming were studied in 15-day-old male mice. Neither early-life stress paradigm affected the expression of stress-related genes (Crh, Avp, Crhr1, Crhr2, Nr3c1, and Nr3c2) and the serum level of corticosterone on PND15. Immunohistochemical analysis was performed on slices of the hippocampus and prefrontal cortex (PFC) with antibodies against a marker of mature neurons (NeuN), of microglia (Iba1), proliferating cells (Ki67), and immature neurons (DCX). We found higher density of ameboid microglia and intermediate microglia in the PFC in groups MS and MD, respectively, than in a control group. In both stressed groups, a higher number of Ki67-positive cells was noted in the dentate gyrus. Thus, in mice, the process of transformation of ameboid microglia into ramified ones as well as a neurogenesis reduction take place during the second postnatal week, whereas early-life stress can disturb these processes in a stress- and region-dependent manner.
Early life is an important period for brain development and behavioral programming. Both reduced maternal care and stress in early life are risk factors for various psychiatric disorders.Here, we hypothesized that females' stressful experience in their early life can lead to a disruption of mother-offspring interactions toward their own progeny. The objective of this study is to assess the effects of mothers' past stressful experience, early-life stress alone or both on behavior in adult male mice. In this study, female mice were allowed to raise their pups either without exposure to stress (normal rearing condition, NC) or with exposure to maternal separation (3h/day, maternal separation, MS) on postnatal days 2-14. Adult F1 female mice who had experienced MS (stressed mothers, SM) or had been reared normally (undisturbed mothers, UM) were used for generating F2 offspring to be or not to be further exposed to early-life stress.We assessed anxiety-like behavior, exploratory activity, locomotor activity, aggression and cognition in four groups of adult F2 males (UM+NC, UM+MS, SM+NC, SM+MS). We found that SM+MS males become more aggressive if agonistic contact is long enough, suggesting a change in their social coping strategy. Moreover, these aggressive males tended to improve longterm spatial memory. Aggressive SM+NC males, in contrast, showed learning impairments. We did not find any significant differences in anxiety-like behavior or exploratory and locomotor activity. Overall, our findings suggest that mothers' early-life experience may have important implications for the adult behavior of their offspring.
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