EFFECTS OF EXOGENOUS HEXACOSANOIC ACID ON BIOCHEMICAL MYELIN COMPOSITION IN WEANING AND POST-WEANING RATS

X-linked Adrenoleukodistrophy (ALD) is characterized by an increase of very long chain fatty acids (VLCFA) in particular of hexacosanoic aci d (HA), in tissues and fluids. The biochemical abnormality is due to t he dysfunction of peroxisomal degradation of VLCFA. To-date it is uncl ear if the demyelination which characterizes this disease is the direc t consequence of HA accumulation. In order to investigate whether the large amounts of exogenous HA could affect myelin synthesis, 500 mu g of this fatty acid dissolved in peanut oil were administered daily and by gavage to newborn rats. Since myelin is actively synthesized durin g early neonatal life and it can be altered by environmental factors i ncluding diet, we analyzed lipid and protein composition of myelin aft er 20, 30 and 60 days of HA administration. Our results show that exog enous HA is incorporated in myelin where it determines biochemical alt erations in normal rats having a functioning peroxisomal system. Even though the differences between controls and treated rats are slight, w e observed in test rats, a decrease of 2'3'-cyclic nucleotide 3'-phosp hohydrolase (CNPase) activity and of myelin basic protein (MBP) conten t at any time studied. The decrease of glycolipids (GL) was present on ly after 20 days of treatment. Since these parameters are related to m yelin development, our data lead us to think that the myelin of the tr eated animals is less mature than that of controls.