Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice
P G Bannerman1, A Hahn, S Ramirez
1Neurology Research, Abramson Pediatric Research Center, Children's Hospital of Philadelphia, PA, USA.
Abstract:
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.
Insights
Experimental autoimmune encephalomyelitis (EAE) in mice causes motor neuron dendritic damage and atrophy, contributing to weakness. These findings suggest similar motor neuron issues may occur in progressive multiple sclerosis.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS).
- Progressive MS is characterized by accumulating neurological deficits and spinal cord atrophy.
- Motor neuron dysfunction is implicated in MS-related weakness.
Purpose of the Study:
- To investigate motor neuron changes in MOG peptide-induced EAE in mice.
- To correlate motor neuron abnormalities with clinical weakness and spinal cord pathology.
- To explore potential parallels between EAE motor neuron pathology and progressive MS.
Main Methods:
- Induction of EAE in adult male C57BL/6 mice using MOG peptide and CFA.
- Monitoring of clinical signs and pathological changes in the spinal cord.
- Assessment of motor neuron morphology, dendritic integrity, and neurofilament expression.
Main Results:
- EAE mice exhibited spinal cord inflammation, demyelination, and axonal fragmentation early on.
- Spinal cord atrophy developed by 14 weeks, despite reduced inflammation.
- Motor neuron dendrites were disrupted early, and perikaryal atrophy appeared later; no significant motor neuron loss was observed.
Conclusions:
- Motor neuron dendritic abnormalities and atrophy, rather than neuron loss, likely contribute to weakness in this EAE model.
- These findings suggest that motor neuron pathology may play a significant role in progressive multiple sclerosis.
- Further research is warranted to confirm these parallels in human MS patients.
