Cholesterol synthesis is down-regulated during regeneration of peripheral nerve.
The discovery of apolipoprotein E synthesis and secretion by injured peripheral nerve to the hypothesis that endoneurial apolipoprotein E serves to salvage degenerating myelin cholesterol. This salvaged cholesterol could then be reutilized by Schwann cells during remyelination via uptake through low-density lipoprotein receptors. As a test of this hypothesis, we measured the rate of cholesterol synthesis in rat sciatic nerve endoneurium during development and at various times following a crush injury at 50 days of age. In control nerves [14C]acetate incorporation into cholesterol and 3-hydroxy-3-methylglutaryl-CoA reductase activity were closely linked throughout development, indicating that reductase activity in nerve, as in other tissues, is a good indicator of cholesterol's synthetic rate. In the crushed nerves cholesterol synthesis fell to nearly zero during the first week after the crush. There was a partial recovery during the second to fourth weeks, but unlike that of other lipids, cholesterol synthesis remained well below control nerve values throughout most of the 15-week post-crush period examined. Thus, cholesterol synthesis is at very low levels during the myelination of regenerating axons. These results are consistent with a receptor-mediated down-regulation of cholesterol synthesis by lipoproteins, and would be expected if Schwann cells were utilizing an external source of cholesterol as postulated above.
Goodrum
J F
JF
Biological Sciences Research Center, University of North Carolina, Chapel Hill 27599.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis*; D015536:Down-Regulation; D005990:Glycerol / Q000378:metabolism; D006651:Histocytochemistry; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration; D051381:Rats; D012584:Sciatic Nerve / Q000378:metabolism / Q000502:physiology*
D000085:Acetates; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D005990:Glycerol