Characterization of adult hippocampal neurogenesis in adult and aged genetically diverse mice

Adult hippocampal neurogenesis-the generation of new neurons in the adult brain-declines with age, contributing to cognitive deficits in aging. While the majority of mammalian studies on neurogenesis have utilized inbred mouse strains, these models do not fully capture the genetic diversity of humans, limiting the translational relevance of their findings. The Diversity Outbred (DO) mouse model, a genetically heterogeneous population, provides a promising alternative to traditional inbred strains. In this study, we investigated how genetic diversity influences hippocampal neurogenesis by comparing neurogenesis in adult and aged Diversity Outbred (DO) mice with the commonly used C57BL/6J inbred strain. While both strains exhibited a decline in neurogenesis with age, DO mice showed significantly lower levels of neurogenesis compared to C57BL/6J mice, even in young adults. Additionally, we observed that the wild-derived CAST/EiJ strain, one of the eight founder strains in the DO model, contributed to this reduction in neurogenesis. Our findings highlight the importance of genetic diversity in neurogenesis research and suggest that the DO model may better represent human genetic diversity associated with age-related decline in neurogenesis.