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Journal of Lipid Research, Vol 37, 1953-1961, Copyright © 1996 by Lipid Research, Inc.
SD Turley, DK Burns, CR Rosenfeld and JM Dietschy
Several lines of evidence have suggested that central nervous system
development and function depend upon a supply of cholesterol that comes
from low density lipoproteins (LDL-C). These studies test this hypothesis
directly by measuring in vivo the uptake of LDL-C in nine regions of the
central nervous system at five different stages of development in the fetal
and neonatal sheep. The concentration of LDL-C in the plasma decreased from
49 mg/dl in the fetus 90 days before birth (-90 days) to only 10 mg/dl at
-13 days. By 17 days postnatal this value increased to nearly 60 mg/dl.
Throughout the period of development between -90 days (very early fetus)
and 17 days (late neonatal animal) the weight of the brain increased
32-fold (from 2.3 to 73.6 g) and the content of cholesterol rose 100-fold
(from 8.6 to 876 mg), yet there was no detectable LDL-C uptake in any of
nine areas of the central nervous system at any stage of development
(clearances of < 2 microliters/h per g). This was true even in the -90
day fetus prior to closure of the blood brain barrier. In contrast, LDL-C
clearance by the adrenal gland increased dramatically (from 91 to 348
microliters/h per g) as it also did in the liver (from 36 to 85
microliters/h per g) during fetal development. These studies strongly
suggest, therefore, that cholesterol carried in LDL plays little or no role
in the process of sterol acquisition during brain development or in
cholesterol turnover in the mature central nervous system. Changes in
circulating LDL-C concentration, therefore, should have no effect on brain
function.
ARTICLES
Brain does not utilize low density lipoprotein-cholesterol during fetal and neonatal development in the sheep
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235-8887, USA.
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