Regular Exercise Modiﬁes Histopathological Outcomes of Pharmacological Treatment in Experimental Autoimmune Encephalomyelitis

Frontiers in Neurology, 2018 · DOI: 10.3389/fneur.2018.00950 · Published: November 20, 2018

Simple Explanation

The study investigates how exercise impacts the effectiveness of drugs used to treat multiple sclerosis (MS) in an animal model. Specifically, it looks at the combination of treadmill exercise with either dimethyl fumarate (DMF) or glatiramer acetate (GA). Mice were given treadmill exercise for 4 weeks before being induced with experimental autoimmune encephalomyelitis (EAE), an animal model for MS, and then continued for 6 weeks. After their first clinical relapse, they were treated with either DMF or GA. The results showed that exercise, when combined with drug treatments, could modify the effects of these treatments. For example, exercised mice treated with GA showed reduced signs of astrocyte activity, while those treated with DMF had increased microglial/macrophage response, both associated with clinical improvements.

Study Duration

6 weeks

Participants

96 female C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
Exercised-GA treated animals demonstrated decreased astrocytic response in the spinal dorsal horn with an improvement in the paw print pressure.
2
Exercised-DMF treated animals showed an increased microglial/macrophage response on both ventral and dorsal horn that were associated with clinical improvement and synaptic motoneuron inputs density.
3
Prior regular exercise can modify the effects of pharmacological treatment administered after the ﬁrst relapse in a murine model for MS.

Research Summary

The study investigates the potential of prior regular exercise to modify the effects of pharmacological treatments, specifically glatiramer acetate (GA) and dimethyl fumarate (DMF), in a murine model of multiple sclerosis (MS). The researchers found that exercise, when combined with GA, led to decreased astrocytic response in the spinal dorsal horn and improved paw print pressure, suggesting a positive effect on neuropathic pain or allodynia. Combining exercise with DMF resulted in an increased microglial/macrophage response in both the ventral and dorsal horns, which was associated with clinical improvement and increased synaptic motoneuron inputs density, indicating a potential synergistic response of exercise and DMF treatment.

Practical Implications

Optimizing MS Treatment

An active lifestyle may enhance the effectiveness of disease-modifying therapies (DMTs) for individuals with multiple sclerosis.

Neuropathic Pain Management

Glatiramer acetate (GA) and dimethyl fumarate (DMF) have the potential to reduce inflammatory profiles that may contribute to the attenuation of neuropathic pain in EAE model.

Synaptic Stability and Circuitry Preservation

Prior regular exercise can modify the effects of pharmacological treatment administered after the first relapse in a murine model for MS, resulting in synaptic stability and circuitry preservation.

Study Limitations

1
The exercise protocol used herein did not alter the development of the disease
2
Diﬀerent EAE models, as well as diﬀerent volume, intensity and duration of exercise, may aﬀect ﬁnal conclusions.
3
Future studies are necessary to evaluate the relationship between leptin and inﬂammation in EAE mice.

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