Hippocampal neurogenesis changes in a sex and region-specific manner in adult mice subjected to maternal separation as an early life stress.

Abstract

Introduction: Early life stress (ELS) might produce long lasting changes in hippocampal neurogenesis and increase the vulnerability to stress-related disorders later in adulthood. Objective: The analysis of immature granule cell densities in the hippocampal dentate gyrus (DG) between male and female mice subjected to ELS. Methods: Female and male C57BL/6J mice were subjected to 3h daily maternal separation (MS) for 21 days since birth. In day 60, mice underwent a single 2h restriction stress (RS) and sacrificed 24 hours after. The experimental groups were: Control, RS, MS, MS+RS. The DG was analyzed using immunohistochemistry against DCX following cell stereology to obtain cell densities according to their developmental morphology (Type A: round DCX+ cells, Type B: one-process DCX+ cell, Type C: ramified DCX+ cell). Results: DG neurogenesis changes in a sex-dependent manner, being altered in female mice but not male MS+RS. Female DCX+ Type C density (latest stages of cell immaturity) increases after ELS, significantly in the MS+RS group and with a tendency in the MS alone, compared to the Control. This was also observed to be region-specific in females, with the ventral DG beholding these changes but not the dorsal part. In the ventral DG, female and male MS groups present differences within each other, but not between their controls, which may indicate sex differences in the effects of stress. Conclusion: These differential neurogenic responses to stress depending on the sex and region could explain neurobiological basis behind pathologies like depression. Funding: PID2020-117463RB-I00, P20-00460, UMA20-FEDERJA-112, Ayuda predoctoral 'Plan propio de Investigación de la Universidad de Málaga' (convocatoria 2021) and FPU21/01318. University of Málaga.