Update from 2015 Most Valuable Presentation Recipient: The role of milk Lactoferrin on neurodevelopment and cognition: A dose response, randomized trial

Bing Wang, School of Medicine, Xiamen University, China, and School of Animal and Veterinary Sciences, Charles Sturt University, Sydney, Australia

Yue Chen1, Zhiqiang Zheng1, Xi Zhu1, Yujie Shi2, Dandan Tian1, Fengjuan Zhao1, Ni Liu1,
Petra S. Hüppi3, Frederic A. Troy II14 and Bing Wang1,5
1. School of Medicine, Xiamen University, China;
2. Nestlé Research Center, Beijing, China;
3. Department of Biochemistry and Molecular Medicine, University of California School of Medicine, Davis;
4. Division of Development and Growth, Department of Paediatrics, University of Geneva School of Medicine, Switzerland;
5. School of Animal and Veterinary Sciences, Charles Sturt University, Sydney, Australia

Lactoferrin (Lf) is a sialic acid (Sia)-rich, iron-binding milk glycoprotein that has multifunctional health benefits, including improving neural development and cognition. The aim of this study was to investigate the dose-response effect of milk Lf intervention on gene expression in the hippocampus of postnatal piglets during neurodevelopment.

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 GeneChips representing 20,201 S.scrofa genes. 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 2014). The selected protein expression was analyzed using western blot and immunohistochemistry techniques.

Low-dose Lf activated neurotrophin signalling pathways and modulated expression of genes associated with neurodevelopment, learning and 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.

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(s): Medical school of Xiamen University, China, Nestlé Research Centre-Beijing

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