Lipid Metabolism During Early Stages of Wallerian Degeneration in the Rat Sciatic Nerve

We examined changes in biosynthetic capacity of sciatic nerve during the early stages of Wallerian degeneration, utilizing a model that permits exclusion of nonresident cells from degenerating nerve. Sciatic nerve segments were placed in either 5‐μm pore (allowing infiltration of nonresident cells) or 0.22‐μm pore (excluding nonresident cells) Millipore diffusion chambers and then implanted in the peritoneal cavity of the same 32‐34‐day‐old rat. At times up to 7 days post‐surgery, nerve segments from the chambers, as well as control segments from the contralateral sciatic nerve, were removed and their capacity to incorporate radioactive precursors into lipids and proteins assayed in vitro. In nerve segments from both the 0.22‐ and 5‐μm pore chambers, incorporation of [14C]acetate into total lipids was decreased relative to control by 50% at 12 h postsurgery and by 85% at day 3. This decreased incorporation of [14C]acetate reflects primarily decreased de novo synthesis of cholesterol and of fatty acyl residues incorporated into glycerolipids and sphingolipids. There was a preferentially decreased synthesis of cerebrosides and cholesterol (components enriched in myelin) relative to other lipids, while cholesterol esters and free fatty acids (products of membrane degradation) accounted for a greater proportion of the greatly reduced levels of total lipid label. In contrast to [14C]acetate, incorporation of [3H]glycerol into lipids was increased up to fourfold, relative to control, 1 day after nerve transection. This increased incorporation of [3H]glycerol does not reflect de novo synthesis of lipids (which is decreased), but rather removal of toxic fatty acyl residues derived from degradation of myelin lipids; these toxic compounds must be removed by resynthesis into nonmyelin glycerolipids and cholesterol esters. The inhibition of de novo synthesis of myelin lipids in Schwann cells during the early stages of Wallerian degeneration occurs independently of hematogenously‐derived cells. We suggest that Wallerian degeneration rapidly results in some breakdown of myelin, and that the increased free fatty acid levels resulting from degradation of myelin lipids inhibit the de novo synthesis of new myelin lipid.