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-microns pore (allowing infiltration of nonresident cells) or 0.22-microns 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 postsurgery, 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-microns 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.(ABSTRACT TRUNCATED AT 250 WORDS)