EFFECT OF DIETARY GLYCOMACROPEPTIDE AND CHOLESTEROL ON CORTICAL GANGLIOSIDE- AND GLYCOPROTEIN-BOUND N-ACETYLNEURAMINIC ACID IN YOUNG RATS

Abstract

Background: Sialic acid and cholesterol are present in human milk and accumulate rapidly in the brain during development. Infant formulas contain little sialic acid or cholesterol. Sialic acid and cholesterol supplementation increase cortical ganglioside and glycoprotein sialic acid and cholesterol in animal models, respectively. Doseresponse studies and those varying both sialic acid and cholesterol intake are lacking. Objective: The purpose of this study was to determine the effects of bovine casein glycomacropeptide (CGMP) and dietary cholesterol on cortical ganglioside- and glycoprotein-bound sialic acid accumulation in young rats. Design/Methods: Dams were fed a nutritionally complete rat diet with 0 or 0.5% cholesterol by weight throughout pregnancy and lactation. Litters were culled to 8 pups on postnatal day (P) 1. Coagulated milk was removed from the stomach of P1 pups and the cholesterol concentration determined. After weaning, two pups from each litter were allocated to one of four diets varying in CGMP (provided approximately 0, 20, 40 and 80 mg sialic acid/kg d-1) and the same cholesterol concentration as their dams. In the first experiment, the dams’ litters were weaned on P17 to the sialic acid-supplemented diets and sacrificed on P32. In the second experiment, litters were weaned on P21 to the diet of their dams. Pups consumed the dams’ diets until P24 or P33 and their assigned sialic acid-supplemented diets thereafter. The pups were sacrificed between P38 and P47, 14 days after the initiation of the sialic acid-supplemented diets. On the day of sacrifice, pups were decapitated and their brains immediately frozen on dry ice. Gangliosides and glycoproteins were extracted from the cortex and the sialic acid concentration determined. Results: Maternal cholesterol intake increased total milk cholesterol (p = 0.0009). In pups sacrificed on P32, CGMP increased cortical ganglioside sialic acid in a doseresponse manner (p for trend = 0.007). In the same experiment, dietary cholesterol independently increased ganglioside sialic acid (p = 0.02). In pups sacrificed between P38 and P47, cholesterol intake increased glycoprotein sialic acid (p = 0.030). Conclusions: Increased sialic acid and cholesterol consumption during the first 4 weeks of postnatal brain growth influenced brain composition in rats.