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Dietary Cholesterol and the Origin of Cholesterol in the Brain of Developing Rats¹

John Edmond^*,2, Rose A. Korsak^*, Jack W. Morrow^*, George Torok-Both and Don H. Catlin

^* Department of Biological Chemistry Department of Pharmacology ^* Department of Mental Retardation Research Center, University of California-Los Angeles School of Medicine, Los Angeles, CA 90024

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.

KEY WORDS: • cholesterol • milk • brain development • deuterium-labeled cholesterol • rats

¹ This study was supported by grants from the U.S. Public Health Service, HD11496 and HD06576. Preliminary results from this study were presented at the 8th Congress of the International Association for the Scientific Study of Mental Deficiency, Dublin, Ireland, August 21–24, 1988 [Edmond, J., Korsak, R. A., Anestad, N. & Morrow, J. W. (1989) Milk cholesterol and the developing brain. Proc. 8th Congress IASSMD (in press)]. Recent data contained in this report were presented at the 74th Annual Meeting of the Federation of American Societies for Experimental Biology, April 1–5, 1990, Washington, DC [Edmond, J., Korsak, R. A., Morrow, J. W., Torok-Both, G. & Catlin, D. H. (1990) The origin of cholesterol in brain of the developing rat. FASEB J. 4: A532 (abs.)].

² To whom correspondence should be addressed.

Manuscript received 12 December 1990. Revision accepted 21 March 1991.

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