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Updated: May 31, 2026
Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis
Published on: September 9, 2022
The MAO inhibitor phenelzine improves functional outcomes in mice with experimental autoimmune encephalomyelitis
Travis Musgrave1, Curtis Benson, Grace Wong
1Centre for Neuroscience, University of Alberta, Edmonton, AB, Canada.
Abstract:
Multiple sclerosis (MS) and the animal model, experimental autoimmune encephalomyelitis (EAE), are both accompanied by motor and non-motor symptoms. Pathological changes in the activities of key neurotransmitters likely underlie many of these symptoms. We have previously described disturbances in the levels of 5-hydroxytryptamine (5-HT/serotonin), noradrenaline (NE) and γ-aminobutyric acid (GABA) in a mouse model of EAE. The potential therapeutic effect of a drug that targets these three neurotransmitters, the antidepressant and anti-panic drug phenelzine (PLZ), was assessed in mice with MOG(35-55) induced EAE. The neurotransmitter content of EAE and control tissue after PLZ administration was first evaluated by HPLC. The ability of PLZ treatment to modulate EAE disease course and clinical signs was then assessed. Daily PLZ treatment, starting seven days after disease induction, delayed EAE onset, reduced disease severity in the chronic phase and was associated with substantial improvements in exploratory behavior and a novel measure of sickness and/or depression. Upon completion of the experiment, PLZ's effects on histopathological markers of the disease were examined. No differences were observed in T cell infiltration, microglia/macrophage reactivity, demyelination or axonal injury in PLZ-treated spinal cords. However, EAE mice treated with PLZ showed a normalization of 5-HT levels in the ventral horn of the spinal cord that might account for the improvements in behavioral outcomes. These results demonstrate the therapeutic potential of MAO inhibitors such as PLZ in MS. Additionally, the behavioral changes observed in EAE mice indicate that alterations in non-motor or 'affective' measures may be valuable to consider in addition to traditional measures of gross locomotor function.
Insights
Phenelzine (PLZ) treatment improved multiple sclerosis (MS) symptoms and behavior in mice by normalizing serotonin levels, without altering key pathological markers. This suggests MAO inhibitors may offer therapeutic potential for MS.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), exhibit motor and non-motor symptoms linked to neurotransmitter imbalances.
- Previous research identified altered levels of serotonin (5-HT), noradrenaline (NE), and gamma-aminobutyric acid (GABA) in EAE mouse models.
Purpose of the Study:
- To evaluate the therapeutic potential of phenelzine (PLZ), a drug targeting 5-HT, NE, and GABA, in a mouse model of MS (MOG(35-55) induced EAE).
- To assess PLZ's effects on neurotransmitter levels, EAE disease course, clinical signs, histopathology, and behavioral outcomes.
Main Methods:
- Neurotransmitter levels in EAE and control mice were analyzed using High-Performance Liquid Chromatography (HPLC) after PLZ administration.
- Mice with EAE were treated daily with PLZ starting seven days post-induction.
- Disease course, clinical signs, exploratory behavior, sickness/depression behaviors, and histopathological markers (T cell infiltration, microglia/macrophage reactivity, demyelination, axonal injury) were evaluated.
Main Results:
- Daily PLZ treatment delayed EAE onset and reduced chronic phase severity.
- PLZ administration significantly improved exploratory behavior and sickness/depression measures.
- No significant differences were found in T cell infiltration, microglia/macrophage reactivity, demyelination, or axonal injury in PLZ-treated EAE mice.
- PLZ treatment normalized 5-HT levels in the ventral horn of the spinal cord.
Conclusions:
- Phenelzine (PLZ) demonstrates therapeutic potential for MS by improving behavioral outcomes and reducing disease severity in an EAE model.
- The observed behavioral improvements correlate with normalized spinal cord serotonin (5-HT) levels, suggesting a key mechanism of action.
- MAO inhibitors like PLZ warrant further investigation for MS treatment, highlighting the importance of assessing non-motor symptoms alongside traditional locomotor measures.
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