The effects of coenzyme Q10 and resveratrol treatment on the leukocyte counts and muscle morphology of SJL/J mice with dysferlinopathy : a qualitative microscopic investigation

Abstract

The Dysferlinopathies are a form of Muscular Dystrophy specifically affecting muscles of the shoulder and pelvic girdles; which result from the autosomal recessive inheritance of one of a few mutant variants of the dysferlin gene which encodes the dysferlin protein. The dysferlin protein product is hypothesized to be involved in sarcolemmal vesicle fusion with a disrupted muscle fiber’s plasma membrane, in effect resealing the disruption before a potentially damaging immune response is able to take place. Dysferlinopathic muscle presents extensively with inflammatory characteristics. Mouse models are widely used in the study of Dysferlinopathy, as the mouse dysferlin gene possesses an overall amino acid sequence homology to the human gene in excess of ninety percent, and is also inherited in an autosomal recessive pattern. The SJL/J mouse model was the model of choice in the current study as it demonstrates characteristics that resemble the most common human condition due to the presentation of a dysferlin deficiency as well as a changed inflammatory profile in the muscles. Implementation of this animal model involved the treatment of SJL/J mice over a 90 day period with the anti-oxidant supplements Resveratrol and Coenzyme Q10 separately and in combination, to achieve immune modulation. Modulation of inflammation could, in this disease process, assist in delaying the degeneration processes of muscle fibers with inherently defective healing mechanisms, possibly affording the response to degenerating fibers an extended survival time before complete muscle homeostasis is lost. The anti-oxidants were administered in order to suppress inflammation and thus prevent the immune response to degenerating muscle from causing the additional and untimely death of muscle cells. The leukocyte counts as well as muscle fiber morphology of two muscle complexes were investigated at conclusion of the 90 day experimental period. Differential white blood cell counts did not provide a clear answer as to which therapeutic regime would be the best remedy for Dysferlinopathy sufferers; but muscle biopsy data revealed that Resveratrol does indeed display anti-inflammatory properties at the tissue level and that Coenzyme Q10 does afford a degree of membrane protection to the muscle fibers at an ultrastructural level. From this study it can be concluded that effective therapy could be achieved through the administration of either high levels of Coenzyme Q10 (120mg/kg/day) or combination Resveratrol/Coenzyme Q10 (60:40mg/kg/day); as findings supported beneficial effects on muscle groups of both significantly- and insignificantly-disease-affected muscle complexes. However, in the more significantly-affected muscle group, combination treatment seemed to be favourable to a greater extent than treatment with high levels of Coenzyme Q10 in exclusivity, due to the cooperative effect of combination treatment on muscle health at the tissue level. Accordingly, combination Resveratrol/Coenzyme Q10 supplement administration is recommended through the findings of this study for the maintenance of comprehensive muscle health in sufferers of Dysferlinopathy. For future studies, extensive research focused on immunohistochemistry and proteomics of dysferlin gene and protein expression within Pectoralis and Gluteus complex muscles may lead to a more comprehensive understanding of the ultrastructural and morphological findings in both affected and unaffected animal models utilised in this study. Copyright