Importance of exogenous saturated fatty acids during brain development and myelination in mice

Abstract

was transported into the brain and incorporated into brain lipids. The labelled stearic acid taken up was partly metabolized in the brain either by elongation or by degradation and in situ resynthesis of fatty acids. The activity of oleic acid and mono-unsaturated chains was detectable. The labelled acids were incorporated into lipids or subcellular particles following characteristic kinetics, which showed a diminution by 24 hrs. When analyzing the evolution of each lipid, the phospholipids followed this pattern, but the cerebrosides and free fatty acids did not. The cerebrosides increased up to 50 hrs, while the free fatty acids remained stable, suggesting a physical binding between membranes and these acids. Myelin lipid radioactivity increased up to 3 days. Most of the activity was found in phospholipids; their fatty acids were labelled in saturated as well as in polyunsaturated homologues. However, sphingolipids, especially cerebrosides, also contained large amounts of radioactivity, mainly found in very long chain fatty acids such as lignoceric acid. The presence of unesterified fatty acids was observed. Unlike other lipids, these molecules were found in constant amounts, expressed in radioactivity per mg myelin lipid. The subcutaneously injected stearic acid was taken up by the brain through the blood-brain-barrier and incorporated into synaptosomal lipids as well as into other brain compartments. Phospholipids were potent acceptors. Moreover, a high level of radioactivity occurred in non-esterified fatty acids. A large amount of radioactivity was measured in isolated neurons and astrocytes. The bloodbrain relationship for stearic acid varied during development. Subcutaneously injected (I1’C) stearic acid was taken up by brain with related changes from birth to maturity. Total lipid radioactivity reached a maximum at 18 days of age and decreased afterwards until adulthood. However, specific radioactivity presented a higher value at 1 day of age and declined from then on. The injected acid was taken up at any age and partly metabolized in the brain either by elongation or by degradation in situ and resynthesis of new fatty acids. It was also desaturated and the oleic acid formed was eventually elongated. The incorporation of labelled stearic acid into brain lipid varied with the age of the injected animal.