Cross-fostering affects microglia and cell death in the hippocampus of female and male degu pups

Parental care is essential for social, behavioural, and neural development of offspring. Disruption of parental care, for example through parental separation, can negatively affect offspring development in rodents. While previous work has focused on maternal and paternal deprivation, the effects of cross-fostering, another form of parental-offspring instability, on brain development remain poorly understood. Such disruptions are thought to induce stress, which in turn can suppress neurogenesis and increases inflammation and apoptosis in the hippocampus, with effects that often differ between sexes. Given that degus (Octodon degus) are born precocial and form strong attachments with their parents early in life, this study aimed to investigate the effect of cross-fostering on hippocampal development in female and male degu pups. At postnatal day 8, degus were assigned to either control (pups remained with parents and littermates), partial cross-foster (one pup per litter was cross-fostered), or full cross-foster (the entire litter was cross-fostered) conditions. At weaning (5-weeks-old), offspring brains were collected for immunohistochemistry to examine dentate gyrus volume, density of pyknotic cells, density of immature neurons, and number and morphology of microglia. Both types of cross-fostering reduced hippocampal cell death in both sexes relative to controls, while no significant effects were observed in the dentate gyrus volume or density of immature neurons. Cross-fostering did not affect total microglia density in either sex however full cross-fostered females had fewer amoeboid microglia compared to female controls. Together, these findings indicate that cross-fostering affects hippocampal microglia and cell death in pups, potentially disrupting circuit refinement and plasticity during development, with effects that vary by cross-fostering type, sex, and hippocampal region.