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STUDY: Physical exercise in MS-related fatigue: changes in gene expression profile

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  • STUDY: Physical exercise in MS-related fatigue: changes in gene expression profile

    Physical exercise in multiple sclerosis-related fatigue: changes in gene expression profile

    N. Tellez, P. Mulero, M. Neri, H. Avellon-Liaņo, M. Archanco, R. Almansa (Valladolid, ES)

    Background and purpose: Multiple sclerosis (MS) related fatigue is a challenging symptom with unknown etiology. Physical exercise is a treatment option. Exercise modifies the gene expression profile in other conditions different from MS. We here aimed to explore the effect of the physical exercise, on the gene expression profile, in a sample of MS patients with fatigue who satisfactorily responded to the training.

    Methods: Prospective and longitudinal study. Fourteen MS patients and 15 age matched healthy voluntaries (HV) participated in the study. We included relapsing remitting MS, age 18-50 and clinical and treatment stability for the last 3 months. Patients followed a six month aerobic physical exercise program. Fatigue was assessed, using the Modified Fatigue Impact Scale at baseline and at month sixth. Blood samples were collected at the same time points from patients and HV. Total RNA was extracted from blood samples using the PAXgene blood RNA system. All microarrays were subjected to quality and filtering criteria. These were assessed on Principal Component AnalysisPlots and Boxwhisker Plot. Mann Whitney test was used to identify genes differentially expressed between groups at the level of significance p < 0.05 with Benjamini-Hochberg multiple testing corrections. After obtaining the different gene profiles we used Ingenuity pathway analysis 8.5 (IPA) in order to indentify the functions and pathways related with this genes.

    Results: RNA samples from four patients did not fulfill the quality criteria, and were excluded from the study. Ten MS patients and 15 HV were finally included. Seven patients (70%) improved their fatigue status after the exercise program, and these were considered for the gene analysis. Comparison between MS and HV at baseline showed 1018 genes differentially expressed (653 over expressed and 358 under expressed in the MS group). After the exercise program the genetic profile changed in the MS group, with only 360 genes differentially expressed compared to HV. This would suggest that exercise could favor a normalization of the gene profile in patients. Fifty five intracellular signaling pathways were identified to be related with the genes expressed.

    Conclusion: Physical exercise modulates the molecular hallmark in those MS patients who improve their fatigue status. This finding could explain some of the mechanisms involved in the symptom.
    Dave Bexfield