Fatty Acids from Degenerating Myelin Lipids Are Conserved and Reutilized for Myelin Synthesis During Regeneration in Peripheral Nerve

Abstract: Following nerve crush, cholesterol from degenerating myelin is conserved and reutilized for new myelin synthesis during nerve regeneration. The possibility that other myelin lipids are salvaged and reutilized has not been investigated previously. We examined the fate of myelin phospholipids and their fatty acyl moieties following nerve crush by electron microscopic autoradiography of myelin lipids prelabeled with [³H]oleate or [2-³H]-glycerol. Both precursors were incorporated predominantly (>90%) into phospholipids; >85% of the [³H]oleate was incorporated as oleate, with the remainder in longer-chain fatty acids. Before nerve crush, both labels were restricted to myelin sheaths. Following nerve crush and subsequent regeneration, over half the label from [³H]oleate, but little from [2-³H]glycerol, remained in nerve. The oleate label was present as fatty acyl moieties in phospholipids and was localized to newly formed myelin sheaths. Among the extracellular soluble lipids within the degenerating nerve, the bulk of the labeled phospholipids floated at the same density as lipoprotein particles. These data indicate that myelin phospholipids are completely hydrolyzed during nerve degeneration, that at least half the resultant free fatty acids are salvaged and reutilized for new myelin synthesis, and that these salvaged fatty acids are transported by a lipoprotein-mediated mechanism similar to that functioning in cholesterol reutilization.