Premium
Differential DM20 mRNA expression distinguishes two distinct patterns of spontaneous recovery from murine autoimmune encephalomyelitis
Author(s) -
Mathisen Peter M.,
Kawczak Julie A.,
Yu Min,
Johnson Justin M.,
Tuohy Vincent K.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1106
Subject(s) - remyelination , experimental autoimmune encephalomyelitis , multiple sclerosis , proteolipid protein 1 , myelin , myelin basic protein , immunology , myelin proteolipid protein , medicine , encephalomyelitis , central nervous system
Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS) mediated by T cells responding to CNS myelin proteins. Immunization of SWXJ mice with the immunodominant p139‐151 peptide of myelin proteolipid protein (PLP) results in a relapsing‐remitting pattern of EAE characterized by incomplete remyelination during clinical recovery. In the present study we observed two distinct clinical patterns of spontaneous remission during recovery from EAE, viz., sustained remission involving continuous neurologic improvement and aborted remission involving modest transient clinical improvement. We hypothesized that the ability to recover from autoimmune demyelination was directly linked to remyelination events that recapitulated developmental processes. Quantitative immunocytochemistry of CNS tissue showed decreased demyelination in mice undergoing sustained remission compared to mice undergoing aborted remission. Quantitative RT‐PCR analysis showed elevated expression of DM20, the developmental isoform of PLP, in CNS tissue from mice undergoing sustained remission compared to mice undergoing aborted recovery. Moreover, DM20 expression was similarly elevated in CNS tissue from mice undergoing sustained recovery from EAE relapse. Our data indicate that expression of the developmental DM20 isoform of PLP is intimately associated with decreased demyelination and sustained clinical recovery from EAE. Thus, DM20 gene expression may provide an appropriate molecular target for promoting CNS remyelination and may serve as a useful marker for predicting clinical outcome and assessing the effectiveness of strategies aimed at promoting CNS tissue repair during autoimmune demyelinating disease. J. Neurosci. Res. 64:542–551, 2001. © 2001 Wiley‐Liss, Inc.