Sialic Acid and Sialylated Oligosaccharide Supplementation during Lactation Improves Learning and Memory in Rats

Nutrients. 2018 Oct 16;10(10):1519. doi: 10.3390/nu10101519.


Sialic acids (Sia) are postulated to improve cognitive abilities. This study evaluated Sia effects on rat behavior when administered in a free form as N-acetylneuraminic acid (Neu5Ac) or conjugated as 6'-sialyllactose (6'-SL). Rat milk contains Sia, which peaks at Postnatal Day 9 and drops to a minimum by Day 15. To bypass this Sia peak, a cohort of foster mothers was used to raise the experimental pups. A group of pups received a daily oral supplementation of Neu5Ac to mimic the amount naturally present in rat milk, and another group received the same molar amount of Sia as 6'-SL. The control group received water. After weaning, rats were submitted to behavioral evaluation. One year later, behavior was re-evaluated, and in vivo long-term potentiation (LTP) was performed. Brain samples were collected and analyzed at both ages. Adult rats who received Sia performed significantly better in the behavioral assessment and showed an enhanced LTP compared to controls. Within Sia groups, 6'-SL rats showed better scores in some cognitive outcomes compared to Neu5Ac rats. At weaning, an effect on polysialylated-neural cell adhesion molecule (PSA-NCAM) levels in the frontal cortex was only observed in 6'-SL fed rats. Providing Sia during lactation, especially as 6'-SL, improves memory and LTP in adult rats.

Keywords: 6′-sialyllactose; cognitive development; infant formula; milk oligosaccharides; sialic acid.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Dietary Supplements*
  • Female
  • Frontal Lobe / chemistry
  • Lactation*
  • Lactose / administration & dosage
  • Lactose / analogs & derivatives
  • Learning / drug effects*
  • Long-Term Potentiation / drug effects
  • Male
  • Memory / drug effects*
  • Milk / chemistry
  • N-Acetylneuraminic Acid / administration & dosage*
  • Neural Cell Adhesion Molecule L1 / analysis
  • Oligosaccharides / administration & dosage*
  • Oligosaccharides / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Sialic Acids / analysis


  • 6'-sialyllactose
  • Neural Cell Adhesion Molecule L1
  • Oligosaccharides
  • Sialic Acids
  • polysialyl neural cell adhesion molecule
  • N-Acetylneuraminic Acid
  • Lactose