Related Experiment Video
Updated: Mar 8, 2026
Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Prolonged stimulation of a brainstem raphe region attenuates experimental autoimmune encephalomyelitis
Pernille M Madsen1, Stephanie S Sloley2, Alberto A Vitores2
1The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, USA; Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Abstract:
Multiple sclerosis (MS), a neuroinflammatory disease, has few treatment options, none entirely adequate. We studied whether prolonged electrical microstimulation of a hindbrain region (the nucleus raphe magnus) can attenuate experimental autoimmune encephalomyelitis, a murine model of MS induced by MOG35-55 injection. Eight days after symptoms emerged, a wireless electrical stimulator with an attached microelectrode was implanted cranially, and daily intermittent stimulation was begun in awake, unrestrained mice. The thoracic spinal cord was analyzed for changes in histology (on day 29) and gene expression (on day 37), with a focus on myelination and cytokine production. Controls, with inactive implants, showed a phase of disease exacerbation on days 19-25 that stimulation for >16days eliminated. Prolonged stimulation also reduced numbers of infiltrating immune cells and increased numbers of myelinated axons. It additionally lowered genetic expression of some pro-inflammatory cytokines (interferon gamma and tumor necrosis factor) and platelet-derived growth factor receptor alpha, a marker of oligodendrocyte precursors, while raising expression of myelin basic protein. Studies of restorative treatments for MS might profitably consider ways to stimulate the raphe magnus, directly or via its inputs, or to emulate its serotonergic and peptidergic output.
Insights
Electrical stimulation of the nucleus raphe magnus reduced symptoms in a multiple sclerosis (MS) mouse model. This approach improved myelination and reduced inflammation, offering potential new therapeutic avenues for MS.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Multiple sclerosis (MS) is a chronic neuroinflammatory disease with limited treatment options.
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for studying MS pathogenesis.
Purpose of the Study:
- To investigate the therapeutic potential of nucleus raphe magnus (NRM) electrical microstimulation in an EAE mouse model.
- To assess the effects of NRM stimulation on histological and molecular markers of demyelination and inflammation.
Main Methods:
- EAE was induced in mice using MOG35-55 peptide.
- Following symptom onset, mice received daily intermittent electrical microstimulation of the NRM via a wireless implant.
- Spinal cord tissues were analyzed for histology (myelination, immune cell infiltration) and gene expression (cytokines, myelin proteins) at specified time points.
Main Results:
- NRM stimulation significantly attenuated disease exacerbation observed in control mice.
- Stimulated mice exhibited reduced immune cell infiltration and increased numbers of myelinated axons in the thoracic spinal cord.
- Gene expression analysis revealed decreased pro-inflammatory cytokines and oligodendrocyte precursor markers, alongside increased myelin basic protein expression.
Conclusions:
- Prolonged electrical microstimulation of the NRM demonstrates a restorative effect in a murine model of MS.
- Targeting the NRM, potentially through its serotonergic and peptidergic pathways, represents a promising strategy for developing novel MS therapies.
More Related Videos
08:47Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
26:48Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007