QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (92) Citing Articles via Google Scholar Google Scholar Articles by Mason, J. L. Articles by Matsushima, G. K. Search for Related Content PubMed PubMed Citation Articles by Mason, J. L. Articles by Matsushima, G. K.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 1, 2000, 20(15):5703-5708

Insulin-Like Growth Factor-1 Inhibits Mature Oligodendrocyte Apoptosis during Primary Demyelination

J. L. Mason¹, P. Ye², K. Suzuki³, A. J. D'Ercole², and G. K. Matsushima^{1, 4}

¹ Curriculum in Neurobiology and University of North Carolina Neuroscience Center, Departments of ² Pediatrics, ³ Pathology and Laboratory Medicine, and ⁴ Microbiology and Immunology and Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599

Metabolic insult results in apoptosis and depletion of mature oligodendrocytes during demyelination. To examine the role of insulin-like growth factor-1 (IGF-1) during acute demyelination and remyelination in the adult CNS, we exposed transgenic mice that continuously express IGF-1 (IGF-1 tg) to cuprizone intoxication. Demyelination was observed within the corpus callosum in both wild-type and IGF-1 tg mice 3 weeks after exposure to cuprizone. Wild-type mice showed significant apoptotic mature oligodendrocytes and a dramatic loss of these cells within the lesion that resulted in near complete depletion and demyelination by week 5. In contrast, the demyelinated corpus callosum of the IGF-1 tg mice was near full recovery by week 5. This rapid recovery was apparently caused by survival of the mature oligodendrocyte population because apoptosis was negligible, and by week 4, the mature oligodendrocyte population was completely restored. Furthermore, despite demyelination in both wild-type and IGF-1 tg mice, oligodendrocyte progenitors accumulated only in the absence of mature oligodendrocytes and failed to accumulate if the mature oligodendrocytes remained as demonstrated in the IGF-1 tg mice. These results suggest that IGF-1 may be important in preventing the depletion of mature oligodendrocytes in vivo and thus facilitates an early recovery from demyelination.

Key words: insulin-like growth factor-1; oligodendrocytes; progenitors; myelin; demyelination; apoptosis; mice; transgenic

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20155703-06$05.00/0

This article has been cited by other articles:

				J. Staiger, M. J. Lueben, D. Berrigan, R. Malik, S. N. Perkins, S. D. Hursting, and P. F. Johnson C/EBP{beta} regulates body composition, energy balance-related hormones and tumor growth Carcinogenesis, May 1, 2009; 30(5): 832 - 840. [Abstract] [Full Text] [PDF]

				K. A. Irvine and W. F. Blakemore Remyelination protects axons from demyelination-associated axon degeneration Brain, June 1, 2008; 131(6): 1464 - 1477. [Abstract] [Full Text] [PDF]

				S. Chandran, D. Hunt, A. Joannides, C. Zhao, A. Compston, and R. J.M Franklin Myelin repair: the role of stem and precursor cells in multiple sclerosis Phil Trans R Soc B, January 12, 2008; 363(1489): 171 - 183. [Abstract] [Full Text] [PDF]

				B. Emery, H. S. Cate, M. Marriott, T. Merson, M. D. Binder, C. Snell, P. Y. Soo, S. Murray, B. Croker, J.-G. Zhang, et al. Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination PNAS, May 16, 2006; 103(20): 7859 - 7864. [Abstract] [Full Text] [PDF]

				R. S. Settivari, S. Bhusari, T. Evans, P. A. Eichen, L. B. Hearne, E. Antoniou, and D. E. Spiers Genomic analysis of the impact of fescue toxicosis on hepatic function J Anim Sci, May 1, 2006; 84(5): 1279 - 1294. [Abstract] [Full Text] [PDF]

				P. Mana, D. Linares, S. Fordham, M. Staykova, and D. Willenborg Deleterious Role of IFN{gamma} in a Toxic Model of Central Nervous System Demyelination Am. J. Pathol., May 1, 2006; 168(5): 1464 - 1473. [Abstract] [Full Text] [PDF]

				V. C. Russo, P. D. Gluckman, E. L. Feldman, and G. A. Werther The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain Endocr. Rev., December 1, 2005; 26(7): 916 - 943. [Abstract] [Full Text] [PDF]

				Q.-L. Cui, W.-H. Zheng, R. Quirion, and G. Almazan Inhibition of Src-like Kinases Reveals Akt-dependent and -independent Pathways in Insulin-like Growth Factor I-mediated Oligodendrocyte Progenitor Survival J. Biol. Chem., March 11, 2005; 280(10): 8918 - 8928. [Abstract] [Full Text] [PDF]

				N Wilczak, G S. Ramsaransing, J Mostert, D Chesik, and J De Keyser Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis Multiple Sclerosis, February 1, 2005; 11(1): 13 - 15. [Abstract] [PDF]

				J. L. Mason, S. Xuan, I. Dragatsis, A. Efstratiadis, and J. E. Goldman Insulin-Like Growth Factor (IGF) Signaling through Type 1 IGF Receptor Plays an Important Role in Remyelination J. Neurosci., August 20, 2003; 23(20): 7710 - 7718. [Abstract] [Full Text] [PDF]

				P. Ye, R. Bagnell, and A. J. D'Ercole Mouse NG2+ Oligodendrocyte Precursors Express mRNA for Proteolipid Protein But Not Its DM-20 Variant: A Study of Laser Microdissection-Captured NG2+ Cells J. Neurosci., June 1, 2003; 23(11): 4401 - 4405. [Abstract] [Full Text] [PDF]

				G. R. John, S. C. Lee, and C. F. Brosnan Cytokines: Powerful Regulators of Glial Cell Activation Neuroscientist, February 1, 2003; 9(1): 10 - 22. [Abstract] [PDF]

				E. Chaum and H. Yang Transgenic Expression of IGF-1 Modifies the Proliferative Potential of Human Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., December 1, 2002; 43(12): 3758 - 3764. [Abstract] [Full Text] [PDF]

				P. Ye, L. Li, R. G. Richards, R. P. DiAugustine, and A. J. D'Ercole Myelination Is Altered in Insulin-Like Growth Factor-I Null Mutant Mice J. Neurosci., July 15, 2002; 22(14): 6041 - 6051. [Abstract] [Full Text] [PDF]

				J. L. Mason, K. Suzuki, D. D. Chaplin, and G. K. Matsushima Interleukin-1{beta} Promotes Repair of the CNS J. Neurosci., September 15, 2001; 21(18): 7046 - 7052. [Abstract] [Full Text] [PDF]

				E. J. McMahon, D. N. Cook, K. Suzuki, and G. K. Matsushima Absence of Macrophage-Inflammatory Protein-1{alpha} Delays Central Nervous System Demyelination in the Presence of an Intact Blood-Brain Barrier J. Immunol., September 1, 2001; 167(5): 2964 - 2971. [Abstract] [Full Text] [PDF]

				D. E. Varlam, M. M. Siddiq, L. A. Parton, and H. Rüssmann Apoptosis Contributes to Amphotericin B- Induced Nephrotoxicity Antimicrob. Agents Chemother., March 1, 2001; 45(3): 679 - 685. [Abstract] [Full Text]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help