Cholesterol Esters of the Human Brain During Fetal and Early Postnatal Development: Content and Fatty Acid Composition

Abstract

The content and fatty acid composition of cholesterol esters of the human brain during development from 13 weeks' gestation up to 26 months of age was studied. The three major brain areas, the forebrain, cerebellum, and the brain stem, were studied separately. The concentration of the esters in each brain region was the highest at the earliest fetal age of 13 weeks and fell during growth. However, transient rises in the concentration were observed, at about birth in the forebrain and at 4–5 months after birth in the cerebellum The peak concentration during the transient period (125–150 μg/g fresh tissue of forebrain and 100–125 μg/g of cerebellum) was similar to the concentrations observed in the two parts respectively during early fetal ages. The brain stem also showed similar transient peak at about a few weeks before birth, but only when the esters were expressed as amount per cell. In absolute terms, a clear transient period was evident in the forebrain between birth and 9 months, while in the cerebellum or the brain stem, the total amount of the esters increased up to about 1 year of age and then remained almost unchanged. The major fatty acids of the esters were palmitic, palmitoleic, stearic, oleic, linoleic and arachidonic acid. Most of these fatty acids showed certain changes in relative proportions during development. Thus, in the forebrain, palmitic and oleic acid decreased from about 32% and 40% (weight percentages) at 13–15 weeks of gestation to about 20% and 25% respectively at 26 months of age. During this period, linoleic and arachidonic acid increased from about 3% and S% to about 10% and 24%, respectively. Most of these changes occurred after birth. The cerebellum and the brain stem differed only slightly from the forebrain in either the fatty acid composition or the pattern of the developmental changes in the composition.

Cholesterol homeostasis: a key to prevent or slow down neurodegeneration

“…This transient increase appears to be a universal phenomenon, because it has been found in all mammalian brains that have been studied so far. In particular, (Yusuf et al, 1981) reported that in humans the CE concentrations in the three main parts of brain, forebrain, cerebellum, and brainstem, were highest at 13–15 weeks and rapidly fell during growth. Transient rises in CE concentrations were also seen around birth in the forebrain and few months after birth in the cerebellum, a period coinciding with the onset of active myelination in the respective brain areas.…”

Effect of Malnutrition and Subsequent Rehabilitation on the Development of Mouse Brain Myelin

“…These changes may take place in the relative mole proportions of the major lipids (cholesterol, phospholipids, galactolipids) (Horrocks, 1968;Banik and Davison, 1969;Dalal and Einstein, 1969;Norton and Poduslo, 1973) or proteins (Wiggins et al, 1976), or of the different components of a major lipid class, e.g., the ganglio-sides (Suzuki et al, 1967) and the phospholipids (Cuzner and Davison, 1968;Fishman et al, 1975). Changes may also take place in the relative proportions of the constituent fatty acids of a particular lipid, e.g., the cerebrosides (Krigman and Hogan, 1976) or the cholesterol esters (Eto and Suzuki, 1972;Yusuf et al, 1981). Relatively little information is available as regards the possible effect of nutritional deprivation on this developmental aspect of myelination.…”

Molecular markers of brain cholesterol homeostasis are unchanged despite a smaller brain mass in a mouse model of cholesteryl ester storage disease

“…for EC levels in different regions of the brain in either humans or animal models. However, one study using autopsied brain tissue from neonates at 1-26 months of age found similar EC concentrations in the forebrain, cerebellum, and brain stem (Yusuf et al, 1981). These concentrations were mostly in the range of 40-70 μg/g wet tissue weight (i.e., 0.04-0.07 mg/g) which are comparable to the EC levels found in the Lal +/+ mice across all ages in the current study (Figure 2a).…”

“…The brain does have an internal lipoprotein production and transport system operating mostly between astrocytes and neurons as discussed in extensive detail elsewhere (Orth & Bellosta, 2012;Petrov et al, 2016;Pfrieger & Ungerer, 2011;Wang & Eckel, 2014). A third feature is that in the healthy, mature individual more than 99% of the cholesterol in the CNS is unesterified although during phases of fetal and early postnatal development a transient elevation in the level of esterified cholesterol (EC) has been detected (Alling & Svennerholm, 1969;Kinney et al, 1994;Yusuf et al, 1981).…”