Abstract
For reasons that are not well understood, central nervous system repair in multiple sclerosis is often minimal. We present evidence, in a murine model of chronic progressive multiple sclerosis, that genetic factors can substantially influence remyelination, axonal integrity, and neurologic function. Four inbred mouse strains, SJL, B10.D1-H2q, FVB, and SWR, developed extensive inflammatory demyelination by 3 months after infection with Theiler's murine encephalomyelitis virus. Demyelination continued lifelong in SJL and B10.D1-H2q mice, accompanied by axonal injury, minimal remyelination, and progressive motor dysfunction. In contrast, FVB and SWR mice showed less axonal injury, progressive remyelination, and stabilization of motor function. Genetic dominance of the reparative traits was demonstrated by crossing remyelinating strains (FVB and SWR) with nonremyelinating strains (SJL and B10.D1-H2q). All F1 mice developed a phenotype identical to FVB and SWR, showing extensive remyelination, partial preservation of axons, and preserved motor function. Analyses of viral RNA and antigen, immune cell infiltration, and antiviral antibody titers did not predict the phenotypic differences between strains. These results highlight the significant extent to which hereditary factors can control disease course and demonstrate that the switch from a pathogenic to a reparative phenotype can occur even after prolonged inflammatory demyelination.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 46-57 |
| Number of pages | 12 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 64 |
| Issue number | 1 |
| State | Published - Jan 2005 |
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Keywords
- CNS repair
- Genetics
- Multiple sclerosis
- Remyelination
- Theiler's virus
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neuroscience(all)
Cite this
Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis. / Bieber, Allan J.; Ure, Daren R.; Rodriguez, Moses.
In: Journal of Neuropathology and Experimental Neurology, Vol. 64, No. 1, 01.2005, p. 46-57.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis
AU - Bieber, Allan J.
AU - Ure, Daren R.
AU - Rodriguez, Moses
PY - 2005/1
Y1 - 2005/1
N2 - For reasons that are not well understood, central nervous system repair in multiple sclerosis is often minimal. We present evidence, in a murine model of chronic progressive multiple sclerosis, that genetic factors can substantially influence remyelination, axonal integrity, and neurologic function. Four inbred mouse strains, SJL, B10.D1-H2q, FVB, and SWR, developed extensive inflammatory demyelination by 3 months after infection with Theiler's murine encephalomyelitis virus. Demyelination continued lifelong in SJL and B10.D1-H2q mice, accompanied by axonal injury, minimal remyelination, and progressive motor dysfunction. In contrast, FVB and SWR mice showed less axonal injury, progressive remyelination, and stabilization of motor function. Genetic dominance of the reparative traits was demonstrated by crossing remyelinating strains (FVB and SWR) with nonremyelinating strains (SJL and B10.D1-H2q). All F1 mice developed a phenotype identical to FVB and SWR, showing extensive remyelination, partial preservation of axons, and preserved motor function. Analyses of viral RNA and antigen, immune cell infiltration, and antiviral antibody titers did not predict the phenotypic differences between strains. These results highlight the significant extent to which hereditary factors can control disease course and demonstrate that the switch from a pathogenic to a reparative phenotype can occur even after prolonged inflammatory demyelination.
AB - For reasons that are not well understood, central nervous system repair in multiple sclerosis is often minimal. We present evidence, in a murine model of chronic progressive multiple sclerosis, that genetic factors can substantially influence remyelination, axonal integrity, and neurologic function. Four inbred mouse strains, SJL, B10.D1-H2q, FVB, and SWR, developed extensive inflammatory demyelination by 3 months after infection with Theiler's murine encephalomyelitis virus. Demyelination continued lifelong in SJL and B10.D1-H2q mice, accompanied by axonal injury, minimal remyelination, and progressive motor dysfunction. In contrast, FVB and SWR mice showed less axonal injury, progressive remyelination, and stabilization of motor function. Genetic dominance of the reparative traits was demonstrated by crossing remyelinating strains (FVB and SWR) with nonremyelinating strains (SJL and B10.D1-H2q). All F1 mice developed a phenotype identical to FVB and SWR, showing extensive remyelination, partial preservation of axons, and preserved motor function. Analyses of viral RNA and antigen, immune cell infiltration, and antiviral antibody titers did not predict the phenotypic differences between strains. These results highlight the significant extent to which hereditary factors can control disease course and demonstrate that the switch from a pathogenic to a reparative phenotype can occur even after prolonged inflammatory demyelination.
KW - CNS repair
KW - Genetics
KW - Multiple sclerosis
KW - Remyelination
KW - Theiler's virus
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M3 - Article
C2 - 15715084
AN - SCOPUS:13244299201
VL - 64
SP - 46
EP - 57
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 1
ER -