title: Lactoferrin Promotes Early Neurodevelopment and Cognition in Postnatal Piglets by Upregulating the BDNF Signaling Pathway and Polysialylation.
abstract: Lactoferrin (Lf) is a sialic acid (Sia)-rich, iron-binding milk glycoprotein that has multifunctional health benefits. Its potential role in neurodevelopment and cognition remains unknown. To test the hypothesis that Lf may function to improve neurodevelopment and cognition, the diet of postnatal piglets was supplemented with Lf from days 3 to 38. Expression levels of selected genes and their cognate protein profiles were quantitatively determined. The importance of our new findings is that Lf (1) upregulated several canonical signaling pathways associated with neurodevelopment and cognition; (2) influenced ~10 genes involved in the brain-derived neurotrophin factor (BDNF) signaling pathway in the hippocampus and upregulated the expression of polysialic acid, a marker of neuroplasticity, cell migration and differentiation of progenitor cells, and the growth and targeting of axons; (3) upregulated transcriptional and translational levels of BDNF and increased phosphorylation of the cyclic adenosine monophosphate (cAMP) response element-binding protein, CREB, a downstream target of the BDNF signaling pathway, and a protein of crucial importance in neurodevelopment and cognition; and (4) enhanced the cognitive function and learning of piglets when tested in an eight-arm radial maze. The finding that Lf can improve neural development and cognition in postnatal piglets has not been previously described.
authors.affiliation: School of Medicine, Xiamen University, 361005, Xiamen, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.forename: Yujie
authors.initials: Y
authors.lastname: Shi
authors.forename: Dandan
authors.initials: D
authors.lastname: Tian
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Zhao
authors.forename: Ni
authors.initials: N
authors.lastname: Liu
authors.forename: Petra S
authors.initials: PS
authors.lastname: Hüppi
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Troy
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D003071:Cognition / Q000187:drug effects*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects / Q000254:growth & development*; D009473:Neuronal Plasticity / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D034421:Sus scrofa; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D007781:Lactoferrin; D019158:N-Acetylneuraminic Acid; D006854:Hydrocortisone