REGIONAL VARIATION IN CHOLESTEROL-SYNTHESIS AND LOW-DENSITY-LIPOPROTEIN TRANSPORT IN THE BRAIN OF THE FETUS, NEWBORN AND ADULT ANIMAL

These studies were designed to characterize the regional differences i n cholesterol concentration throughout the brain of the developing she ep and hamster and to learn more about the origin of this cholesterol by measuring in vivo the rates of cholesterol synthesis and low densit y lipoprotein-cholesterol clearance by different regions of the centra l nervous system in these animal models. In both species whole brain c holesterol concentration increased several fold throughout fetal and e arly neonatal life. There were marked regional differences in choleste rol concentration throughout the brain, with the concentration being g reatest in the areas richest in myelin. In both hamsters and sheep the differences in cholesterol concentration between the various regions correlated strongly with the differences in the rate of cholesterol sy nthesis. In no region of the central nervous system of the fetal and n eonatal sheep could significant rates of LDL transport be detected Tog ether these studies show that cholesterol deposition in the rapidly de veloping central nervous system of the fetal and neonatal animal does not require the uptake of low density lipoprotein-cholesterol from the plasma, but instead appears to be critically dependent on the de novo synthesis of cholesterol within the brain itself. (C)1997, Medikal Pr ess.