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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 3, 2007, 27(1):27-34; doi:10.1523/JNEUROSCI.4017-06.2007

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 ISI 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 ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Lehmann, H. C. Articles by Sheikh, K. A. Search for Related Content PubMed PubMed Citation Articles by Lehmann, H. C. Articles by Sheikh, K. A.

 Previous Article  |  Next Article 

Cellular/Molecular
Passive Immunization with Anti-Ganglioside Antibodies Directly Inhibits Axon Regeneration in an Animal Model

Helmar C. Lehmann,^1,3 * Pablo H. H. Lopez,^1 * Gang Zhang,¹ Thien Ngyuen,¹ Jiangyang Zhang,² Bernd C. Kieseier,³ Susumu Mori,² and Kazim A. Sheikh¹

Departments of ¹Neurology and ²Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, and ³Department of Neurology, Heinrich Heine University, D-40225 Düsseldorf, Germany

Correspondence should be addressed to Dr. Kazim A. Sheikh, Department of Neurology, Johns Hopkins Hospital, 600 North Wolfe Street, 509 Pathology Building, Baltimore, MD 21205. Email: ksheik{at}jhmi.edu

Recent studies have proposed that neurite outgrowth is influenced by specific nerve cell surface gangliosides, which are sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. For example, the endogenous lectin, myelin-associated glycoprotein (MAG), is reported to bind to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders, autoantibodies against GD1a or other gangliosides are implicated in pathophysiology. Because of neurobiological and clinical relevance, we asked whether anti-GD1a antibodies inhibit regeneration of injured axons in vivo. Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after PNS injury in mice. In mutant mice with altered ganglioside or complement expression, inhibition by antibodies was mediated directly through GD1a and was independent of complement-induced cytolytic injury. The impaired regenerative responses and ultrastructure of injured peripheral axons mimicked the abortive regeneration typically seen after CNS injury. These data demonstrate that inhibition of axon regeneration is induced directly by engaging cell surface gangliosides in vivo and imply that circulating autoimmune antibodies can inhibit axon regeneration through neuronal gangliosides independent of endogenous regeneration inhibitors such as MAG.

Key words: gangliosides; axon regeneration; anti-ganglioside antibodies; Guillain–Barré syndrome; passive transfer; animal model

---

Received Sept. 14, 2006; revised Nov. 13, 2006; accepted Nov. 13, 2006.

Correspondence should be addressed to Dr. Kazim A. Sheikh, Department of Neurology, Johns Hopkins Hospital, 600 North Wolfe Street, 509 Pathology Building, Baltimore, MD 21205. Email: ksheik{at}jhmi.edu

This article has been cited by other articles:

				D. Kittaka, M.-i. Itoh, Y. Ohmi, Y. Kondo, S. Fukumoto, T. Urano, O. Tajima, K. Furukawa, and K. Furukawa Impaired hypoglossal nerve regeneration in mutant mice lacking complex gangliosides: Down-regulation of neurotrophic factors and receptors as possible mechanisms Glycobiology, July 1, 2008; 18(7): 509 - 516. [Abstract] [Full Text] [PDF]

				P. H. H. Lopez, G. Zhang, M. A. Bianchet, R. L. Schnaar, and K. A. Sheikh Structural requirements of anti-GD1a antibodies determine their target specificity Brain, July 1, 2008; 131(7): 1926 - 1939. [Abstract] [Full Text] [PDF]

				G. Williams, A. Wood, E.-J. Williams, Y. Gao, M. L. Mercado, A. Katz, D. Joseph-McCarthy, B. Bates, H.-P. Ling, A. Aulabaugh, et al. Ganglioside Inhibition of Neurite Outgrowth Requires Nogo Receptor Function: IDENTIFICATION OF INTERACTION SITES AND DEVELOPMENT OF NOVEL ANTAGONISTS J. Biol. Chem., June 13, 2008; 283(24): 16641 - 16652. [Abstract] [Full Text] [PDF]

				T. Ariga, M. P. McDonald, and R. K. Yu Thematic Review Series: Sphingolipids. Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease--a review J. Lipid Res., June 1, 2008; 49(6): 1157 - 1175. [Abstract] [Full Text] [PDF]

				S. K. Halstead, F. M. P. Zitman, P. D. Humphreys, K. Greenshields, J. J. Verschuuren, B. C. Jacobs, R. P. Rother, J. J. Plomp, and H. J. Willison Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model Brain, May 1, 2008; 131(5): 1197 - 1208. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help