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Cortical demyelination can be modeled in specific rat models of autoimmune encephalomyelitis and is major histocompatibility complex (MHC) haplotype-related.

Abstract
In recent years, a number of histopathologic studies revealed the presence of cortical demyelination in multiple sclerosis (MS). The underlying mechanisms responsible for cortical demyelination are unresolved. Recently, the presence of cortical lesions in autoimmune encephalomyelitis (EAE) induced in marmosets and Lewis rats has been demonstrated. So far, it is not known whether cortical demyelinated lesions are also present in other models of EAE. In this study, we analyzed a large spectrum of different rat strains actively immunized with myelin oligodendrocyte glycoprotein (MOG), a model strongly mimicking MS for cortical demyelination. By using sets of rat strains with the constant EAE-permissive LEW nonmajor histocompatability complex (MHC) genome, but different MHC haplotypes, we demonstrated that considerable cortical demyelination was only found in LEW.1AR1 (RT1) and LEW.1W (RT1) strains. These rat strains have the isotypes and alleles RT1.BD in the MHC II region and RT1.C in the nonclassic MHC I region in common. Because cortical demyelination was most prominent in LEW.1AR1 rats, an additional strong influence is promoted by the RT1.A MHC class I allele. Demyelination was accompanied by microglia infiltration and deposition of immunoglobulins on myelin sheaths. Our study shows that extensive cortical demyelination can be reproducibly induced in certain rat strains by active immunization with MOG. Furthermore, our findings suggest that cortical demyelination in EAE depends on particular combinations of MHC I and class II isotypes and alleles. The mechanisms for this influence and any similar effects in humans will be important to define.
AuthorsMaria K Storch, Jan Bauer, Christopher Linington, Tomas Olsson, Robert Weissert, Hans Lassmann
JournalJournal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 65 Issue 12 Pg. 1137-42 (Dec 2006) ISSN: 0022-3069 [Print] England
PMID17146287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Histocompatibility Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • MOG protein, human
  • Mog protein, rat
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
Topics
  • Alleles
  • Animals
  • Cerebral Cortex (immunology, pathology, physiopathology)
  • Demyelinating Autoimmune Diseases, CNS (genetics, immunology, physiopathology)
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental (immunology, pathology, physiopathology)
  • Female
  • Genetic Predisposition to Disease (genetics)
  • Genotype
  • Haplotypes (genetics)
  • Histocompatibility Antigens (genetics)
  • Histocompatibility Antigens Class I (genetics, immunology)
  • Histocompatibility Antigens Class II (genetics, immunology)
  • Microglia (immunology, pathology)
  • Mutation (genetics)
  • Myelin Proteins
  • Myelin-Associated Glycoprotein (genetics, immunology)
  • Myelin-Oligodendrocyte Glycoprotein
  • Nerve Fibers, Myelinated (immunology, pathology)
  • Rats
  • Rats, Inbred Lew
  • Rats, Mutant Strains

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