Brain Advance Access originally published online on May 18, 2005
Brain 2005 128(8):1877-1886; doi:10.1093/brain/awh550
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Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice
1 Neurology Research, Abramson Pediatric Research Center, Children's Hospital of Philadelphia and 2 Department of Neurology, Thomas Jefferson Hospital, Philadelphia, Pennsylvannia, USA
Correspondence to: David Pleasure MD, Room 516H Abramson Research Building, The Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA, USA E-mail: pleasure{at}email.chop.edu
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 3555 (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.
Key Words: motor neuron; experimental autoimmune encephalomyelitis (EAE); dendrite; axonal degeneration; multiple sclerosis
Abbreviations: CFA = complete Freund's adjuvant; EAE = experimental autoimmune encephalomyelitis; hypoP-NF-H = hypophosphorylated neurofilament heavy; MAP2a = microtubule-associated protein 2a; MBP = myelin basic protein; MOG = myelin oligodendrocyte glycoprotein; PBS = phosphate-buffered saline; YFP = yellow fluorescent protein
Received February 11, 2005. Revised April 4, 2005. Accepted April 21, 2005.
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