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EAE induced CNS inflammation accelerates ALS‐like disease in the hmSOD transgenic rat model
Author(s) -
Harris Brent T.,
Kathryn Bercury K.,
Graber David J.,
Davidson Todd S.,
Merkens Karlina P.,
Hoff Ryan M.,
Hickey William F.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a25-d
Subject(s) - amyotrophic lateral sclerosis , spinal cord , inflammation , medicine , paralysis , experimental autoimmune encephalomyelitis , atrophy , pathology , transgene , genetically modified mouse , encephalomyelitis , multiple sclerosis , central nervous system , immunology , biology , disease , endocrinology , surgery , biochemistry , psychiatry , gene
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no effective therapy in which the degeneration of motor neurons results in atrophy of most muscles, leading to death within several years. Transgenic rats that over‐express the human mutant form of superoxide dismutase (hmSODG93A), found in some familial forms of ALS, are a relatively new animal model of this disease. These animals show progressive weight loss and paralysis at several months of age. In order to determine if inflammation in the spinal cord could alter SOD‐related paralysis, we induced experimental autoimmune encephalomyelitis (EAE) in this animal model prior to signs of SOD‐related clinical symptoms. EAE is an inflammatory and sometimes demyelinating condition of the spinal cord often used as an animal model of multiple sclerosis and is species‐sensitive. WT and SOD rats displayed only mild and self‐limiting EAE with inflammation by histology and immunohistochemistry. Transgenic rats with prior EAE developed more rapid weight loss and earlier onset of paralysis compared to SOD animals without EAE induction. Immunohistochemistry and RT‐PCR were performed on spinal cord tissues isolated at end‐stage of disease from control and experimental animals to compare glial activation and the expression of several inflammatory cytokines. The data show that early, pre‐symptomatic induction of inflammation in the central nervous system of SOD transgenic animals accelerates the course of ALS‐like symptoms. This work is supported by DMS and the ALS Center of DHMC