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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 11, 2007, 27(28):7429-7437; doi:10.1523/JNEUROSCI.1307-07.2007

This Article Full Text Full Text (PDF) Supplemental Data 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 (8) Citing Articles via Google Scholar Google Scholar Articles by Plant, S. R. Articles by Ting, J. P.-Y. Search for Related Content PubMed PubMed Citation Articles by Plant, S. R. Articles by Ting, J. P.-Y.

 Previous Article  |  Next Article 

Neurobiology of Disease
Lymphotoxin ß Receptor (LtßR): Dual Roles in Demyelination and Remyelination and Successful Therapeutic Intervention Using LtßR–Ig Protein

Sheila R. Plant,^1,2 * Heather A. Iocca,^1 * Ying Wang,¹ J. Cameron Thrash,⁴ Brian P. O'Connor,¹ Heather A. Arnett,^1,2 Yang-Xin Fu,⁵ Monica J. Carson,⁴ and Jenny P.-Y. Ting^1,2,3

¹Lineberger Comprehensive Cancer Center, ²Neuroscience Center, and ³Department of Microbiology-Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, ⁴Division of Biomedical Sciences, University of California, Riverside, California 92521, and ⁵Department of Pathology, The University of Chicago, Chicago, Illinois 60637

Correspondence should be addressed to Dr. Jenny P.-Y. Ting, Lineberger Comprehensive Cancer Center, Campus Box 7295, University of North Carolina, Chapel Hill, NC 27599. Email: panyun{at}med.unc.edu

Inflammation mediated by macrophages is increasingly found to play a central role in diseases and disorders that affect a myriad of organs, prominent among these are diseases of the CNS. The neurotoxicant-induced, cuprizone model of demyelination is ideally suited for the analysis of inflammatory events. Demyelination on exposure to cuprizone is accompanied by predictable microglial activation and astrogliosis, and, after cuprizone withdrawal, this activation reproducibly diminishes during remyelination. This study demonstrates enhanced expression of lymphotoxin ß receptor (LtßR) during the demyelination phase of this model, and LtßR is found in areas enriched with microglial and astroglial cells. Deletion of the LtßR gene (LtßR^–/–) resulted in a significant delay in demyelination but also a slight delay in remyelination. Inhibition of LtßR signaling by an LtßR–Ig fusion decoy protein successfully delayed demyelination in wild-type mice. Unexpectedly, this LtßR–Ig decoy protein dramatically accelerated the rate of remyelination, even after the maximal pathological disease state had been reached. This strongly indicates the beneficial role of LtßR–Ig in the delay of demyelination and the acceleration of remyelination. The discrepancy between remyelination rates in these systems could be attributed to developmental abnormalities in the immune systems of LtßR^–/– mice. These findings bode well for the use of an inhibitory LtßR–Ig as a candidate biological therapy in demyelinating disorders, because it is beneficial during both demyelination and remyelination.

Key words: demyelination; cuprizone; glia; Ltß; LtßR; therapy

---

Received July 24, 2006; revised June 1, 2007; accepted June 4, 2007.

Correspondence should be addressed to Dr. Jenny P.-Y. Ting, Lineberger Comprehensive Cancer Center, Campus Box 7295, University of North Carolina, Chapel Hill, NC 27599. Email: panyun{at}med.unc.edu

This article has been cited by other articles:

				M. Dubois-Dalcq, A. Williams, C. Stadelmann, B. Stankoff, B. Zalc, and C. Lubetzki From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases Brain, July 1, 2008; 131(7): 1686 - 1700. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help