Abstract

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.

Highlights

  • Breast feeding is associated with multiple health benefits

  • We evaluated cognitive functions with behavioral and electrophysiological measurements, demonstrating that these sources of sialic acids (Sia) given behavioral and after electrophysiological measurements, demonstrating these sources to of aSia given at at early stages birth maintain cognitive function in adulthoodthat when compared group that early stages after birth maintain cognitive function in adulthood when compared to a group that received a lower amount of Sia, and that the provision of Sia as 6 -sialyllactose (6 -SL) may confer some advantages received a lower amount of Sia, and that the provision of Sia as 6′-SL may confer some advantages over the use of the free form

  • Pioneering studies in the 1980s showed that intraperitoneally exogenous Sia could be incorporated into brain gangliosides and glycoproteins when injected in rat pups [27]

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Summary

Introduction

Breast feeding is associated with multiple health benefits. Infants fed human milk have lower rates of intestinal and autoimmune diseases and food allergies and show higher intellectual quotient (IQ) scores compared to formula-fed infants [1]. The unique composition of human milk plays a key role in optimal development of newborns, and sialic acids (Sia) are considered as one of the components responsible for the multiple benefits. They are present in most mammalian milks, mainly conjugated to proteins and oligosaccharides, and as free monosaccharides. Within this last group of monosaccharides, there are some key core structures such as N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc) and deaminated neuraminic acid (Kdn), which encompass the so-called Sia molecules [2]. Neu5Ac is the only form of Sia synthesized by humans [2] and is present throughout the body, including brain [3]

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