The Biochemistry of Demyelination and Demyelinating Diseases

Abstract

Wallerian degeneration was the first experimental model of demyelination devised and has been widely investigated both structurally and biochemically. After severing a peripheral nerve there is increasing loss of cerebrosides, sphingomyelin, cholesterol and phospholipids, that of the cephalins starting earlier and exceeding that of lecithin [1]. During the first 14 days after neurotomy the decrease of fatty aldehydes exceeds that of phosphatides and of fatty acid esters [2]. The fatty acids of the total lipids [3] decrease at different rates: C16 : 1 and C18 : 2 starting earlier, the PUFA at 16 days. PI remains constant until the 32nd day after injury. Cholesterol esters are found in significant amounts as early as eight days [3]. Loss of lipids, as well as increased neutral proteinase activity [4, 5, 6], proceed until approximately the 32nd day. Then resynthesis of lipids starts and continues up to the 132nd day but the quantity synthesized does not reach the amount seen in the controls [1, 7]. There is overlapping of these processes, and the phagocytosis and catabolism of myelin by the Schwann cells, and esterification of cholesterol. Sequential study [8] reveals that myelin formed last is the first to fall prey to the degenerative process, progressing toward the one laid down first. ¹⁴C-labelled choline, ethanolamine or serine administered during the phase of remyelination in rats are incorporated in greater amounts into the lipids of the regenerating nerve than into the intact control. This is noted up to eight weeks after the injury [7].