Download PDF
J Reconstr Microsurg 2002; 18(6): 495-502
DOI: 10.1055/s-2002-33321
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Peripheral Nerve Regeneration in the Apolipoprotein-E-Deficient Mouse

Eric M. Genden1 , Osamu Watanabe2 , Susan E. Mackinnon2 , Daniel A. Hunter2 , Suzanne R. Strasberg2
  • 1Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York
  • 2Department of Surgery, Division of Plastic Surgery, Washington University School of Medicine, St. Louis, MO
Further Information

Publication History

Publication Date:
14 August 2002 (online)

Also available at
    Permissions and Reprints

ABSTRACT

Apolipoprotein E (apo E) is thought to mediate the reutilization of myelin cholesterol for nerve regeneration. Prior research suggests that apo E is not essential for nerve regeneration following a nerve crush injury. This study was conducted to determine if apo E is essential for nerve regeneration after nerve transection and interposition nerve autograft. Nerve regeneration of transgenic apo E-deficient mice was compared with control mice after a sciatic nerve neurolysis and repair and interposition autograft. Histomorphometric assessment and histology were performed on distal nerve segments to evaluate nerve regeneration. Apo E-deficient mice demonstrated no difference in total fiber number or nerve fiber width when compared with controls; however, the nerve fiber density and percent neural tissue of apo E-deficient mice were significantly less than controls following nerve repair. Apo E deficiency does not affect nerve regeneration. It is likely that the low nerve fiber density and the low percent neural tissue associated with apo E-deficiency result from impairment in the disposal of myelin debris.

KEYWORDS

Peripheral nerve regeneration - Apolipoprotein E - myelin lipids

REFERENCES

  • 1 Popko B, Goodrum J F, Bouldin T W. Nerve regeneration occurs in the absence of apoliprotein E in mice.  J Neurochem . 1993;  60 1155-1158
    PubMedSearch in Google Scholar
  • 2 Goodrum J F, Bouldin T W, Zhang S H. Nerve regeneration and cholesterol reutilization occur in the absence of apolipoproteins E and A-1 in mice.  J Neurochem . 1995;  64 408-416
    PubMedSearch in Google Scholar
  • 3 Mahley R W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.  Science . 1988;  240 622-630
    PubMedSearch in Google Scholar
  • 4 Boyles J K, Zoellner C D, Anderson L J. A role for apolipoprotein E, apolipoprotein A-1, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of rat sciatic nerve.  J Clin Invest . 1989;  83 1015-1031
    PubMedSearch in Google Scholar
  • 5 Goodrum J F, Earnnardt T, Goines N, Bouldin T W. Fate of myelin lipids during degeneration and regeneration of peripheral nerve: an autoradiographic study.  J Neurosci . 1994;  14 357-367
    PubMedSearch in Google Scholar
  • 6 Piedrahita J A, Zhang S H, Hagmaman J R. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells.  Proc Natl Acad Sci . 1992;  89 4471-4475
    PubMedSearch in Google Scholar
  • 7 Zhang S H, Reddick R L, Piedrahita J A, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E.  Science . 1992;  258 468-471
    PubMedSearch in Google Scholar
  • 8 Goodrum J F, Novicki D I. Macrophage-like cells from explant cultures of rat sciatic nerve produce apolipoprotein E.  J Neurosci Res . 1988;  20 457-462
    CrossrefPubMedSearch in Google Scholar
  • 9 Gelman B B, Rifai N, Goodrum J F. Apolipoprotein E is released by rat sciatic nerve during segmental demyelination and remyelination.  J Neuropathol Exp Neurol . 1987;  46 644-652
    PubMedSearch in Google Scholar
  • 10 Snipes G J, McGuire C B, Norden J J, Freeman J A. Nerve injury stimulates the secretion of apolipoprotein E by nonneural cells.  Proc Natl Acad Sci USA . 1986;  83 1130-1134
    PubMedSearch in Google Scholar
  • 11 Ignatius M J, Gebicke-Haeter P J, Pate Skene H J. Expression of apolipoprotein E during nerve degeneration and regeneration.  Proc Natl Acad Sci USA . 1986;  83 1130-1134
    PubMedSearch in Google Scholar
  • 12 Venezie R D, Toews A D, Morell P. Macrophage recruitment in different models of nerve injury: lysozyme as a marker for active phagocytosis.  J Neurosci Res . 1995;  40 99-107
    CrossrefPubMedSearch in Google Scholar
  • 13 Leblank A C, Poduslo J F. Regulation of apolipoprotein E gene expression after injury of the rat sciatic nerve.  J Neurosci Res . 1990;  25 162-171
    CrossrefPubMedSearch in Google Scholar
  • 14 Boyles J K, Notterpek L M, Anderson L J. Accumulation of apolipoproteins in the regenerating and remyelinating mammalian peripheral nerve.  J Biol Chem . 1990;  265 17805-17815
    PubMedSearch in Google Scholar
  • 15 Gelman B B, Rifai N, Goodrum J F, Bouldine T W. Macrophage apolipoprotein synthesis and endoneurial distribution as a response to segmental demyelination.  J Neuropathol Exp Neurol . 1991;  50 383-407
    PubMedSearch in Google Scholar
  • 16 Goodrum J F. Cholesterol from degenerating nerve myelin becomes associated with lipoproteins containing apolipoprotein E.  J Neurochem . 1991;  56 2082-2086
    PubMedSearch in Google Scholar
  • 17 Rothe T, Muller W. Uptake of endoneurial lipoprotein into Schwann cells and sensory neurons is mediated by low density lipoprotein receptors and stimulated after axonal injury.  J Neurochem . 1991;  57 2016-1025
    PubMedSearch in Google Scholar
  • 18 Goodrum J F. Cholesterol synthesis is down-regulated during regeneration of peripheral nerve.  J Neurochem . 1990;  57 2016-2025
    PubMedSearch in Google Scholar
  • 19 Goodrum J F. Cholesterol synthesis in regenerating peripheral nerve is not influenced by serum cholesterol levels.  J Neurochem . 1993;  60 1564-1566
    PubMedSearch in Google Scholar
  • 20 Nathan B P, Bellosta S, Sanan D A. Differential effects of apolipoproteins E3 and E4 on neural growth in vitro.  Science . 1994;  264 850-852
    PubMedSearch in Google Scholar
  • 21 Handelmann G E, Boyles J K, Weisgraber K H. Effects of apolipoprotein E, very low density lipoproteins, and cholesterol on the extension of neurites by rabbit dorsal root ganglion neurons in vitro.  J Lipid Res . 1992;  33 1677-1688
    PubMedSearch in Google Scholar
  • 22 Xin L, Richardson P M, Gervais F, Skamene E. A deficiency of axonal regeneration in C57BL/6J mice.  Brain Res . 1990;  510 144-146
    CrossrefPubMedSearch in Google Scholar