Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice.
Using adult male C57BL/6 mice that express a yellow fluorescent protein transgene in their motor neurons, we induced experimental autoimmune encephalomyelitis (EAE) by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) in complete Freund's adjuvant (CFA). Control mice of the same transgenic strain received CFA without MOG peptide. Early in the course of their illness, the EAE mice showed lumbosacral spinal cord inflammation, demyelination and axonal fragmentation. By 14 weeks post-MOG peptide, these abnormalities were much less prominent, but the mice remained weak and, as in patients with progressive multiple sclerosis, spinal cord atrophy had developed. There was no significant loss of lumbar spinal cord motor neurons in the MOG peptide-EAE mice. However, early in the course of the illness, motor neuron dendrites were disrupted and motor neuron expression of hypophosphorylated neurofilament-H (hypoP-NF-H) immunoreactivity was diminished. By 14 weeks post-MOG peptide, hypoP-NF-H expression had returned to normal, but motor neuron dendritic abnormalities persisted and motor neuron perikaryal atrophy had appeared. We hypothesize that these motor neuron abnormalities contribute to weakness in this form of EAE and speculate that similar motor neuron abnormalities are present in patients with progressive multiple sclerosis.
Bannerman
P G
PG
Neurology Research, Abramson Pediatric Research Center, Children's Hospital of Philadelphia, PA, USA.
Hahn
A
A
Ramirez
S
S
Morley
M
M
Bönnemann
C
C
Yu
S
S
Zhang
G-X
GX
Rostami
A
A
Pleasure
D
D
D000818:Animals; D001284:Atrophy; D001369:Axons / Q000473:pathology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000473:pathology; D003712:Dendrites / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000032:analysis; D063308:Myelin-Oligodendrocyte Glycoprotein; D016900:Neurofilament Proteins / Q000032:analysis; D010641:Phenotype; D010766:Phosphorylation; D013116:Spinal Cord / Q000473:pathology
C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016900:Neurofilament Proteins; C051774:neurofilament protein H