Functional Correlates and Impact of Dietary Lactoferrin Intervention and its Concentration‐dependence on Neurodevelopment and Cognition in Neonatal Piglets

Scope Lactoferrin (Lf), a sialylated milk glycoprotein, promotes early neurodevelopment and cognition. Functional concentrations of Lf, however, remain unknown. Our objective is to determine the concentration‐dependency of Lf on genes associated with neurodevelopment and cognition in neonatal piglets. Methods and results Piglets are given milk replacer with Lf at concentrations of 155 (low) or 285 mg kg ‐1 day ‐1 (high) from postnatal days 3 to 38. Gene expression associated with neurodevelopment, cognition, and cognate proteins were quantitated. This study found 1) The rate of learning and long‐term memory was higher with 155 mg kg ‐1 day ‐1 assessed in an eight‐arm radial maze; 2) Global gene transcription profiling showed this lower concentration upregulated genes and functions correlated with neurodevelopment and cognition, while the higher concentration regulated cellular processes for neuroprotection; 3) Expression of BDNF genes and proteins were higher with both concentrations, while genes regulating BDNF signaling, including SLC6A3, IGF‐1 responded more to the lower concentration; 4) The lower concentration modulated genes in the five highest networks associated with cellularity and neurocognition, while the prevention of neurodevelopmental and neurological pathologies was associated with the higher concentration. Conclusion The lower concentrations of Lf enhanced neurodevelopment and cognition, while higher concentrations are greater neuroprotective, findings of potential novel clinical relevance.