Sex differences in socioemotional behavior and changes in ventral hippocampal transcription across aging in C57Bl/6J mice

Socioemotional health is positively correlated with improved cognitive and physical aging. Despite known sex differences in socioemotional behaviors and the trajectory of aging, the interactive effects between sex and aging on socioemotional outcomes are poorly understood. We performed the most comprehensive assessment of sex differences in socioemotional behaviors in C57Bl/6J mice across aging to date. Compared to males, females exhibited decreased anxiety-like behavior and social preference but increased social re-cognition. With age, anxiety-like behavior, cued threat memory generalization, and social preference in-creased in both sexes. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed transcriptional neuropathology markers in the ventral hippocampus and found age-related changes in genes related to activated microglia, angiogenesis, and cytokines. Sex differences emerged in the timing, direction, and magnitude of these changes, independent of reproductive senescence in aged females. Interestingly, female-specific upregulation of autophagy-related genes correlated with age-related beha-vioral changes selectively in females. These novel findings reveal critical sex differences in trajectories of ventral hippocampal aging that may contribute to sex-and age-related differences in socioemotional out-comes.& COPY; 2023 Elsevier Inc. All rights reserved.

Automated summary

Socioemotional health is linked to improved cognitive and physical aging. However, the interactive effects between sex and aging on socioemotional outcomes are not well understood. In this study, we assessed sex differences in socioemotional behaviors in mice across aging and found that females showed decreased anxiety-like behavior and social preference, but increased social recognition compared to males. We also discovered age-related changes in genes related to microglia activation, angiogenesis, and cytokines in the ventral hippocampus, with sex differences in the timing, direction, and magnitude of these changes.