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.
Keywords: BDNF signaling pathway; Lactoferrin; gene profiling; microarray; neonatal piglet model; neurodevelopment.
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