Metabolic alterations of endoneurial lipids in developing trembler nerve.

In vitro incorporation of [14C]acetate into desheathed sciatic nerve (endoneurium) was studied in developing normal and mutant trembler mice. The total uptake of [14C]acetate peaked 6 days after birth and decreased thereafter for both normal and trembler mice. Substantially less [14C]acetate (approximately 50% of normal) was incorporated in trembler mouse as early as 3 days after birth. In 3 and 6 day-old trembler mice, proportionately less [14C]acetate was incorporated into phospholipids and cerebrosides and more was incorporated into cholesterol. From 9 days, however, less [14C]acetate was incorporated into cholesterol of trembler compared to normal nerve. At later times (greater than or equal to 20 days), the proportion of [14C]acetate in both phospholipids and cerebrosides of trembler nerve was increased above that of controls. Throughout development, the relative incorporation of [14C]acetate into triacylglycerol and cholesteryl esters was about two times higher in trembler than in normal mice. In normal nerve, the 14C-label in free fatty acids increased (4-25%) progressively with age. In contrast, this incorporation in trembler nerves remained constantly low (less than 7%). Morphologically, the nerves of trembler mouse are markedly hypomyelinated. The abnormal myelin sheath undergoes cycles of breakdown and partial regeneration. Thus, the biochemical profile of extended active but perturbed lipid metabolism may provide a basis for the morphologic findings of continued active but ineffective myelination in trembler peripheral nerve.