Maternal immune activation during the lactational period alters offspring behavior, reproductive development, and immune function in mice

Abstract

Exposure to infection during early life can lead to lasting neurodevelopmental changes. Animal models of maternal immune activation (MIA) typically assess neurobehavioral alterations in offspring following a prenatal inflammatory challenge. However, MIA effects on offspring can extend to challenges that occur during the lactational period. In the present study, we adapted previous methods focused on rats and challenged nursing C57BL/6J mouse mothers on postnatal day (P)8 with either the bacterial mimetic lipopolysaccharide (LPS; 250 μg/kg, i.p.) or saline (control, i.p.). By exposing only the mother to LPS, this modeled a postpartum infection in the dam. Similar to the rat model, lactational MIA did not detrimentally alter maternal care but induced displays of maternal sickness, as expected. While neonatal offspring behaviors (e.g., huddling, ultrasonic vocalizations, negative geotaxis) were unaffected, significant effects of lactational MIA emerged in juvenile (e.g., social preference, accelerated reproductive milestones) and adult (e.g., mechanical allodynia, prepulse inhibition) offspring. In a separate set of animals, the developmental programming potential of lactational MIA on immune function was evident following a “second hit” LPS challenge in adulthood (e.g., altered plasma concentrations of interleukin-6 and leukocytes, including neutrophils, and lymphocytes). These findings confirm the generalizability of the lactational MIA model across species and highlight the importance of supporting caregiver health and wellness across the critical nursing period.