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Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis

Item Type:Article
Title:Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis
Creators Name:Vogt, J. and Paul, F.E. and Aktas, O. and Mueller-Wielsch, K. and Doerr, J. and Doerr, S. and Bharathi, B.S. and Glumm, R. and Schmitz, C. and Steinbusch, H. and Raine, C.S. and Tsokos, M. and Nitsch, R. and Zipp, F.
Abstract:OBJECTIVE: Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). METHODS: We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high-precision stereology. RESULTS: Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL-deficient T lymphocytes. INTERPRETATION: Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology.
Keywords:Adoptive Transfer, Apoptosis, Cell Count, Animal Disease Models, Experimental Autoimmune Encephalomyelitis, Lymphocyte Activation, Motor Neurons, Multiple Sclerosis, Nerve Degeneration, Neurons, Spinal Cord, T-Lymphocytes, TNF-Related Apoptosis-Inducing Ligand, Animals
Source:Annals of Neurology
ISSN:0364-5134
Publisher:Wiley (U.S.A.)
Volume:66
Number:3
Page Range:310-322
Date:September 2009
Official Publication:https://doi.org/10.1002/ana.21719
PubMed:View item in PubMed

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