Dietary Cholesterol and the Origin of Cholesterol in the Brain of Developing Rats

Abstract

Milk substitutes containing cholesterol at concentrations lower, equal to or greater than the concentrations found in natural rat milk were fed to artificially reared rat pups from 5 d until 15 or 16 d after birth. Pups reared by their mother served as controls. In one experiment, D7-cholesterol was fed in the milk at four different concentrations. The purpose of the study was to determine whether cholesterol in milk influenced growth and the sterol composition of brain over the period of its most rapid accumulation in this organ. We found that body and brain weights were not different, irrespective of the concentration of cholesterol in the milk substitutes. High concentrations of cholesterol in milk caused a significant increase in cholesterol in liver and plasma, whereas the concentration of cholesterol in brain was not different from the concentration in the brain of controls. The amounts of D7-cholesterol in lung and liver, and in plasma and RBC that pass the brain, were consistent with the concentration fed in the milk and approached 70% of the total content of cholesterol in these organs at the highest concentration fed. Brain, by contrast, contained very small amounts of D7-cholesterol, which could readily be attributed to D7-cholesterol associated with the vascular system of the blood-brain barrier. We found that the sterol composition of brain is not influenced by the concentration of cholesterol in milk and that cholesterol exogenous to brain, even in a hypercholesterolemic condition, does not gain entry to the brain. We conclude that the brain biosynthesizes de novo all the cholesterol it requires.

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

“…However, how these molecules might be transported into and out of the CNS remains unknown. In mammals greater than 95% of the total cholesterol in the brain is synthesized in situ with little uptake of cholesterol from plasma (Edmond et al 1991;Jurevics and Morell 1995). Our detection of sterol glucosides in plasma accompanied by the resulting neuropathology may suggest that the glucose moiety confers greater transport capability into CNS.…”

Desmosterol, the main sterol in rabbit semen: distribution among semen subfractions and its role in the in vitro spermatozoa acrosome reaction and motility

“…Desmosterol has not been found in significant quantities elsewhere in the body except in the brain [26] and testis, and it has been proposed that it is a biochemical marker of puberty in the monkey [27]. Although there is no direct evidence, the presence of this sterol in the PSGs of rabbit semen, which are specifically produced by the prostate, is a unique biological finding and may indicate an active desmosterol synthesis in this accessory sex gland.…”

Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal

“…When the cholesterol concentration in this artificial milk was increased 6-fold, the concentration of cholesterol in the liver also increased 6-fold, but it remained unchanged in the brain. Furthermore, the deuterated cholesterol present in the milk came to label ‫ف‬ 70% of the sterols in the plasma and liver but virtually none of the cholesterol in the brain (132). In baboons administered [ 14 C]cholesterol intravenously, virtually all organs became heavily labeled after 70-85 days.…”