Nerve regeneration and cholesterol reutilization occur in the absence of apolipoproteins E and A-I in mice

Jeffry F. Goodrum*, Thomas W. Bouldin, Sunny H. Zhang, Nobuyo Maeda, Brian Popko

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Apolipoproteins have been implicated in the salvage and reutilization of myelin cholesterol during Wallerian degeneration and the subsequent nerve regeneration. Current evidence suggests that myelin cholesterol complexes with apolipoproteins E and A-I to form lipoproteins that are taken up via low-density lipoprotein receptors on myelinating Schwann cells. We recently reported, however, that apolipoprotein E is not required for nerve regeneration or reutilization of myelin cholesterol. We have now investigated nerve regeneration and the reutilization of cholesterol in mutant mice deficient in both apolipoproteins E and A-I. Morphologic examination of nerves 4 and 12 weeks after crush injury revealed that regeneration proceeded at a normal rate in the absence of these apolipoproteins. Autoradiography of regenerating nerves indicated that prelabeled myelin lipid was reutilized in the regenerating myelin, 3- Hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, was down-regulated in the regenerating nerves, indicative of cholesterol uptake via lipoproteins. Prelabeled myelin cholesterol was present in lipoprotein fractions isolated from crushed nerves of mutant mice. These data suggest that there is considerable redundancy in the process of cholesterol reutilization within nerve, and that apolipoproteins other than apolipoproteins E and A-I may be involved in the recycling of myelin cholesterol.

Original languageEnglish (US)
Pages (from-to)408-416
Number of pages9
JournalJournal of neurochemistry
Volume64
Issue number1
StatePublished - Jan 1995

Keywords

  • Apolipoprotein A-I
  • Apolipoprotein A-IV
  • Apolipoprotein E
  • Gene targeting
  • Nerve regeneration
  • Peripheral nerve

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

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