Biosynthesis of membrane cholesterol during peripheral nerve development, degeneration and regeneration.

Abstract

Biosynthesis of peripheral nerve cholesterol was investigated by the in vivo and in vitro incorporation of [1-14C]-acetate into sciatic endoneurium of normal rats during development, degeneration and regeneration. Labeled sterols were rapidly formed (less than 10 min) within the endoneurial portion of sciatic nerve after [1-14C]acetate administration by intraneural injection. The majority of labeled sterols were initially found in lanosterol and desmosterol. After six hr, the 14C-labeling in both precursors was decreased to minimum, whereas cholesterol became the major labeled product of sterol. As myelination proceeded, the incorporation of [1-14C]acetate into endoneurial cholesterol decreased rapidly and reached a minimum after six mo. In mature adult nerve, an increased proportion of biosynthesis of lanosterol and desmosterol also was demonstrated. The in vitro incorporation of [1-14C]acetate into cholesterol was inhibited during Wallerian degeneration. Instead, cholesteryl esters were labeled as the major sterol product. Such inhibition, however, was not observed in the adult Trembler nerve (Brain Res. 325, 21-27, 1985), which is presumed to be due to a primary metabolic disorder of Schwann cells. The cholesterol biosynthesis was gradually resumed in degenerated nerve by either regeneration of crush-injured nerve or reattachment of the transected nerve. These results suggest that cholesterol biosynthesis in peripheral nerve relies on the axon to provide necessary substrates. De novo synthesis appears to be one of the major sources of endoneurial cholesterol that forms and maintains peripheral nerve myelin.