Sex differences in adult social, cognitive, and affective behavioral deficits following neonatal phlebotomy-induced anemia in mice

Introduction: Anemia is common in prematurely born infants due to blood loss resulting from frequent phlebotomies and may contribute to their neurobehavioral deficits. Preclinical models of phlebotomy-induced anemia (PIA) have revealed metabolic and genomic changes in multiple brain structures of young mice, yet the impact of neonatal PIA on early-life and adult behavior has not been assessed. Methods: The present study employed a range of behavioral measures in phlebotomized anemic neonatal mice to investigate short- and long-term neurodevelopmental effects. PIA from postnatal (P) days 3 to 14 caused sex-specific changes in social behavior, novelty preference, and anxiety at P17 that persisted into adulthood. Results: Our preclinical model suggests that PIA may contribute to acute and long-term behavioral and affective deficits and warrants further substantiation of the observed behavioral phenomena in larger samples. Conclusions: We conclude that this model is a useful tool for beginning to better understand the lasting effect that early-life PIA might have on the developing brain. The differential impact of PIA on male and female subjects warrants further exploration for the development of appropriately targeted interventions.