Multiple sclerosis (MS) is a neurodegenerative disease that occurs mostly in young adults. In France, 110,000 people are estimated to suffer from it with 4,000 to 6,000 new cases each year. MS is a demyelinating autoimmune disease: the immune system attacks certain peptides that make up myelin, causing it to be broken down and disrupting nerve messages. The main target of this process is the central nervous system (CNS). The peripheral nervous system (PNS) is also known to be affected but descriptions are still very limited.
Researchers from the Joliot Institute (SIMoS/DMTS, BAOBAB/NeuroSpin and BioMaps/SHFJ), in collaboration with the Butantan Institute of Sao Paulo (Brazil), studied alterations in the peripheral nervous system in a mouse model of MS. The model used (Experimental Autoimmune Encephalomyelitis (EAE) in mice) is the one that best reproduces the anatomical (CNS inflammation, demyelination of nerve fibers...) and behavioral alterations observed in humans. It is obtained by injecting an antigenic peptide derived from the MOG protein (Myelin Oligodendrocyte Glycoprotein). Using a minimally invasive electrophysiology method, the researchers observe in vivo changes in the excitability of peripheral sensory and motor nerves in EAE individuals compared to a control group. These modifications correspond, on the one hand, to membrane hyperexcitability, likely related to membrane depolarization, and, on the other hand, to the presence of slow conducting sensory and motor nerve fibers, probably related to their demyelination. In parallel, the authors observed, by transmission electron microscopy, a decrease in the thickness of the myelin sheath of the sciatic nerves of EAE mice compared to the control group.
All the results, published in the Journal of Neuroinflammation, tend to show that the immune dysfunction towards the MOG antigen observed in the EAE experimental model and in individuals with MS is attributed to the expression of this antigen not only in the CNS but also in the PNS.
Left pannels: stimulation of caudal nerve and recordings of compound muscle action potential (CMAP) resulting from the activity of all fibres composing the tail muscle. Central pannels: stimulation of sciatic nerve and recordings of CMAP resulting from the activity of all fibers composing the plantar muscle. Right pannels: peripheral nerve myelin sheath analysed by transmission electron microscopy. Top: in a control animal and bottom: in a EAE (MOG) mouse. © N. Bernardes Teixeira et al., 2020
Contact:
Evelyne Benoît (evelyne.benoit@cea.fr)