Neonatal infection produces sex-specific changes in neuroimmune function with no associated deficits in spatial learning in juvenile rats

Immune activation during early development can have profound effects on later immune function, cognition, and behavior. Epidemiological data indicate a strong correlation between early-life immune activation and later diagnosis of disorders such as autism, schizophrenia, and depression. However, there has been little investigation into the impact of sex or early-life immune activation on the developing immune system or the ontogeny of cognitive processes, such as learning. Microglia are the resident immune cells of the brain and affect neural function and behavior. Male rats have more microglia than female rats in the hippocampus (HP) on postnatal day four (P4), suggesting that males may be more vulnerable to the long- term consequences of early-life immune activation than females. We examined the effect of neonatal immune activation ( E.coli ; 1 × 106 CFU/0.1 mL/kg) alone, or following a second immune challenge of LPS (Lipopolysaccharide; 25 μg/mL/kg), during late juvenile development on behavior and microglia function in males and females. Neither neonatal infection nor a second immune activation produced learning deficits. However, neonatal infection produced sex-specific alterations in CD11b, IL- β , and IL-6 in the HP, prefrontal cortex (PFC), and cerebellum. Additionally, we found sex-specific alterations in microglial density in CA3, dentate gyrus, and PFC. These data suggest that neonatal infection produces sex-specific changes in cytokine expression and microglia activation in juveniles, but the consequences of these changes may have a delayed effect on behavioral outcomes.