Vitamin A supplementation increases the uptake of chylomicron retinyl esters into the brain of neonatal rats raised under vitamin A-marginal conditions

Abstract

Background: The most rapid phase of brain development occurs during the neonatal period. Vitamin A (VA; retinol) iscritical for many aspects of this process, including neurogenesis, synaptic plasticity, learning, and memory formation.However, the metabolism of retinol in the neonatal brain has not been extensively explored.Objective: We examined the uptake of VA into the brain in neonatal rats raised under VA-marginal conditions (controlgroup) and assessed the effect of VA supplementation on the uptake of VA into the brain.Methods: Sprague-Dawley neonatal rats (n = 104) nursed by mothers fed a VA-marginal diet were randomly assigned andtreated on postnatal day 4 with an oral dose of either VA (6 mg retinyl palmitate/g body weight) or canola oil as the control,both of which contained 1.8 μCi [3H]retinol. Pups (n = 4/group at a time) were killed at 13 sampling times from 30 min to24 d after dosing. The uptake of total retinol, chylomicron-associated retinyl esters (REs), and retinol bound to retinolbindingprotein (RBP) was estimated with the use of WinSAAM version 3.0.8.Results: Total retinol mass in the brain was closely dependent on its mass in plasma over time (r = 0.91; P < 0.001). Theuptake of retinol into the brain involved both postprandial chylomicrons and RBP, with RBP delivering most of the retinol inthe control group [0.27 nmol/d (RBP) compared with 0.01 nmol/d (chylomicrons)]. VA supplementation increased thefractional uptake of chylomicron REs from 0.3% to 1.2% of plasma pool/d, decreased that of RBP retinol from 0.5% to0.2% of plasma pool/d, and increased the transfer rate of chylomicron REs from nearly zero to 0.7 nmol/d, causing a daylongelevation in the brain mass of total retinol.Conclusion: Postprandial chylomicrons may be a primary mechanism for delivering a recently ingested large dose of VA tothe brain of neonatal rats raised under VA-marginal conditions.