Effects of milk fat globule membrane and its various components on neurologic development in a postnatal growth restriction rat model

J Nutr Biochem. 2019 Jul;69:163-171. doi: 10.1016/j.jnutbio.2019.03.013. Epub 2019 Apr 6.


Background: Milk fat globule membrane (MFGM) is a component of breast milk that consists of glycosylated membrane-bound proteins, polar lipids and carbohydrates originating from the mammary gland plasma membrane. A commercially available bovine MFGM added to infant formula has been shown to improve cognitive development in infants at 12 months of age.

Objective: Considering that MFGM is a complex mixture, our aim was to determine which component(s) may be leading to these cognitive outcomes.

Methods: Growth-restricted rat pups were supplemented with one of five treatments: (a) bovine MFGM, (b) bovine phospholipid concentrate (PL), (c) sialic acid (SIA) at 200 mg/kg body weight (bw) SIA100, (d) SIA at 2 mg/kg bw and (e) nonfat milk as control. Pups were randomized, cross-fostered into litters of 17 pups per dam and supplemented from postnatal day (PD) 2 to PD 21. The following behavioral tests were performed at adulthood: T-Maze Spontaneous Alternation, Novel Object Recognition and Morris Water Maze. Hippocampus was isolated at PD14 and PD21. Expression of four genes were measured including brain-derived neurotrophic factor (BDNF), dopamine receptor 1, (Drd1), glutamate receptor (GluR-1) and ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialytransferase 4 (St8Sia4). Following behavioral testing, brains were collected for nonbiased stereology.

Results: Increased expression of genes due to supplementation was most pronounced at the PD14 time point. The MFGM group exhibited higher T-Maze scores compared to the SIA group (P=.01), whereas the SIA100 group visited the novel object more frequently than the MFGM group in the Novel Object test (P=.02). No differences due to supplementation were found in the Morris Water Maze or nonbiased stereology, CONCLUSIONS: In this trial, MFGM, compared to its individual components, had the largest impact on neurodevelopment in rat pups through up-regulation of genes and improved T-Maze scores compared to the SIA group.

Keywords: Brain development; Gene expression; Milk fat globule membrane; Neurodevelopment; Phospholipid concentrate; Rat pups; Sialic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Glycolipids / chemistry*
  • Glycolipids / pharmacology*
  • Glycoproteins / chemistry*
  • Glycoproteins / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Lipid Droplets
  • Male
  • Maze Learning
  • Rats, Sprague-Dawley


  • Glycolipids
  • Glycoproteins
  • milk fat globule