Early life adversity reduces affiliative behavior with a stressed cagemate and leads to sex-specific alterations in corticosterone responses in adult mice.

Experiencing early life adversity (ELA) alters stress physiology and increases the risk for developing psychiatric disorders. The social environment can influence dynamics of stress responding and buffer and/or transfer stress across individuals. Yet, the impact of ELA on sensitivity to the stress of others and social behavior following stress is unknown. Here, to test the impact of ELA on social and physiological responses to stress, circulating blood corticosterone (CORT) and social behaviors were assessed in adult male and female mice reared under limited bedding and nesting (LBN) or control conditions. To induce stress, one cagemate of a pair-housed cage underwent a footshock paradigm and was then returned to their unshocked partner. CORT was measured in both groups of mice 20 or 90 min after stress exposure, and social behaviors were recorded and analyzed. ELA rearing influenced the CORT response to stress in a sex-specific manner. In males, both control and ELA-reared mice exhibited similar stress transfer to unshocked cagemates and similar CORT dynamics. In contrast, ELA females showed a heightened stress transfer to unshocked cagemates, and sustained elevation of CORT relative to controls, indicating enhanced stress contagion and a failure to terminate the stress response. Behaviorally, ELA females displayed decreased allogrooming and increased investigative behaviors, while ELA males showed reduced huddling. Together, these findings demonstrate that ELA influenced HPA axis dynamics, social stress contagion and social behavior. Further research is needed to unravel the underlying mechanisms and long-term consequences of ELA on stress systems and their impact on behavioral outcomes.

Type of early life adversity confers differential, sex-dependent effects on early maturational milestones in mice.

Early life adversity (ELA) increases risk for negative health outcomes, with sex disparities in prevalence and form of ELA experienced and risk for neuropsychiatric pathology. ELA comes in many forms (e.g. parental neglect/loss, limited access to resources) but whether disparate forms of ELA have common effects on outcomes, and if males and females are equally affected, remains unknown. Epidemiological studies often fail to accurately account for differences in type, timing, and duration of adversity experienced. Rodent models allow precise control of many of these variables. However, differences in the form of ELA, species, strain, housing, and testing paradigms used may contribute to differences in outcomes leading to questions of whether differences are the result of the form of ELA or these other variables. Here, we directly compared two mouse models of ELA, maternal separation (MS) and limited bedding (LB) in males and females on development of the body, motor and visual milestones, stress physiology, and anxiety-like behavior. LB affected timing of early milestones, somatic growth, and stress physiology in both sexes, yet only females showed later anxiety-like behaviors. MS rearing affected males and females similarly in early milestone development, yet only males showed changes in stress physiology and anxiety-like outcomes. These studies provide a platform to directly compare MS and LB models within one lab. The current work advances our understanding of the unique features of ELA that shape early neurodevelopmental events and risk for later pathology, increasing the translational relevance of these ELA models.

Early life adversity reduces affiliative behavior towards a distressed cagemate and leads to sex-specific alterations in corticosterone responses.

Experiencing early life adversity (ELA) alters stress physiology and increases the risk for developing psychiatric disorders. The social environment can influence dynamics of stress responding and buffer and/or transfer stress across individuals. Yet, the impact of ELA on sensitivity to the stress of others and social behavior following stress is unknown. Here, to test the impact of ELA on social and physiological responses to stress, circulating blood corticosterone (CORT) and social behaviors were assessed in adult male and female mice reared under limited bedding and nesting (LBN) or control conditions. To induce stress, one cagemate of a pair-housed cage underwent a footshock paradigm and was then returned to their unshocked partner. CORT was measured in both mice 20 or 90 minutes after stress exposure, and social behaviors were recorded and analyzed. ELA rearing influenced the CORT response to stress in a sex-specific manner. In males, both control and ELA-reared mice exhibited similar stress transfer to unshocked cagemates and similar CORT dynamics. In contrast, ELA females showed a heightened stress transfer to unshocked cagemates, and sustained elevation of CORT relative to controls, indicating enhanced stress contagion and a failure to terminate the stress response. Behaviorally, ELA females displayed decreased allogrooming and increased investigative behaviors, while ELA males showed reduced huddling. Together, these findings demonstrate that ELA influenced HPA axis dynamics, social stress contagion and social behavior. Further research is needed to unravel the underlying mechanisms and long-term consequences of ELA on stress systems and their impact on behavioral outcomes.