Investigating Mechanisms Underlying Differential Effects of Early Life Adversity on Maternal Care, Neuronal Activation, and Social Behavior in Mice

Abstract

Early life adversity (ELA) has been known to predispose individuals to developing neuropsychiatric diseases in later life. ELA is a broad term encompassing a multitude of negative childhood experiences. The history of different types of childhood adversities have been known to result in predispositions to specific neuropsychiatric conditions in later life. Maternal separation combined with early weaning (MSEW) and limited bedding and nesting (LBN) are two rodent models of ELA that are known to cause differential and sex-dependent long-term effects on structural hippocampal plasticity and social behavior in adult mice. Here, we did a comparative study of MSEW and LBN during the postnatal period to characterize model-specific rearing experiences and delineate the mechanisms linking early experiences to the differential outcomes of these models. We found that LBN leads to fragmented maternal care and lower pup body surface temperature, whereas MSEW leads to compensatory higher maternal care-giving. Both the models resulted in lower neuronal activation in the hippocampus. MSEW and LBN models have also been shown to result in impaired social recognition memory in adult males but not females. We investigated the emergence of these sex differences through a longitudinal assessment of social recognition memory in males and females over development and found that these sex differences emerge after puberty. Lastly, we identified increased senescent cells in the subgranular zone (SGZ) in MSEW adult males, as a potential mechanism facilitating the decreased adult neurogenesis after ELA. Further, we found that environment enrichment housing can rescue the increase in senescent cell population in the SGZ. Together, these results provide insights into the early experiences, developmental trajectory, and mechanisms underlying differential outcomes of ELA.