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

Abstract

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)

Fate of myelin lipids during degeneration and regeneration of peripheral nerve: an autoradiographic study

“…Glycerol, which is used in the recycling of fatty acids as well as in de novo lipid synthesis, was especially effective in labeling the fibroblasts' lipid droplets. These results are consistent with previous biochemical studies demonstrating that an increase in the esterification reactions utilizing glycerol is a very early event in Wallerian degeneration (White et al, 1989;Goodrum, 1990). White et al (1989) postulated that the large pool of free fatty acids generated by the breakdown of myelin phospholipids promotes the increase in esterification reactions utilizing glycerol.…”

“…These results are consistent with previous biochemical studies demonstrating that an increase in the esterification reactions utilizing glycerol is a very early event in Wallerian degeneration (White et al, 1989;Goodrum, 1990). White et al (1989) postulated that the large pool of free fatty acids generated by the breakdown of myelin phospholipids promotes the increase in esterification reactions utilizing glycerol. Our data suggest that the fatty acids produced from the catabolism of myelin phospholipids are salvaged by being incorporated into glycerolipids within Schwann cells and fibroblasts (and resident endoneurial macrophages).…”

“…Breakdown of myelin phospholipids and formation of cholesteryl esters are very early events following nerve crush, and still occur when invasion ofthe nerve by macrophages is prevented (White et al, 1989). The fatty acids released during the breakdown of phospholipids are postulated to be reutilized locally in the synthesis of glycerolipids (White et al, 1989).…”

“…Breakdown of myelin phospholipids and formation of cholesteryl esters are very early events following nerve crush, and still occur when invasion ofthe nerve by macrophages is prevented (White et al, 1989). The fatty acids released during the breakdown of phospholipids are postulated to be reutilized locally in the synthesis of glycerolipids (White et al, 1989). At least a portion of the myelin cholesterol in peripheral nerve is also retained within the nerve following a nerve crush, and is subsequently reutilized for the synthesis of new myelin during regeneration of the nerve (Rawlins et al, 1970(Rawlins et al, , 1972.…”

Future Perspectives in Nerve Repair and Regeneration

“…Schwann cells play several important roles in nerve degeneration and regeneration: i. Coincident with axonal injury, Schwann cells in the distal nerve begin to dedifferentiate (Lee et al, 2009). Within 48 h of injury, they start altering their gene expression: expression of myelin proteins (e.g., P0, MAG (myelinassociated glycoprotein)) (Trapp, Hauer, & Lemke, 1988;White et al, 1989) and connexin 32 (a gap junction protein which forms reflexive contacts within individual myelinating SCs at para-nodes) (Hall, 2001) decreases dramatically as a consequence of axonal degeneration distal to the injury site, whereas regeneration associated genes (GAP-43), neurotrophic factors and their receptors, neurotrophin 4/5 (NT-4/5) neuregulin and its receptors, including the low-affinity neurotrophin receptor p75NTR; nerve growth factor (NGF), brainderived neurotrophic factor (BDNF), glial cell linederived neurotrophic factor (GDNF), and insulin-like growth factors (IGFs) (Carroll, Miller, Frohnert, Kim, & Corbett, 1997;Hall, 2001) are upregulated. ii.…”