Background & Aims: The aim of this study was to investigate the dose-response effect of lactoferrin (Lf) intervention on gene expression in the hippocampus of postnatal piglets during neurodevelopment.
Methods: Fifty-one 3-day-old piglets were randomly allocated into a high (H) Lf dose group (n =18), a low (L) Lf dose group (n=17) and a control (C) group (n=16). Piglets were fed sow milk replacer supplemented with Lf at 285 mg/kg/d (H), 155 mg/kg/d (L) and 16 mg/kg/day (C). Piglets were euthanized at 38 days of age. RNA transcript profiling in the hippocampus was carried out using RNA isolated from 10 piglets/gp on Porcine Affymetrix. A TaqMan® Gene expression assay based on qPCR was used to validate the microarray findings. The results were analyzed using the Partek Genomics Suite 6.5 software and Ingenuity System (Chen et al 2015).
Results: Low-dose Lf activated neurotrophin signalling pathways and modulated expression of genes associated with neurodevelopment, learning & memory, including BDNF, FGFR, IRS1 and CAMKK1. Functional analysis showed network signalling impacted brain development, neuron structure and long-term potentiation. In contrast, piglets on the high dose of Lf showed no effect on neurotrophin signalling but an increase in gene expression and signalling pathways leading to cell death/apoptosis and decreased neurogenesis.
Conclusions: Low-dose Lf supplementation up-regulated neurotrophin signalling pathways associated with neurodevelopment and cognition, a finding in contrast to piglets on a high dose of Lf. The molecular mechanism(s) underling this paradoxical finding remains under study.
Funding Source: Medical School, Xiamen Univ & Nestle Research Centre, Beijing.