Differential Leukocyte Counts of SJL/J Mice with Dysferlinopathy Treated with Resveratrol and Coenzyme Q10

Abstract

Dysferlinopathies include Limb-Girdle Muscular Dystrophy type 2B and Miyoshi Myopathy, which exhibit  an autosomal recessive inheritance pattern of the dysferlin gene and characteristic inflammatory infiltrate  in muscle. A study of prospective treatment options was conducted on SJL/J mice, a natural model for dysferlinopathy.  The animals are immunocompetent but have elevated levels of circulating T-cells. A baseline  termination of SJL/J mice was made at 14 weeks, and differential leukocyte counts determined for these  animals through microscopy. After administration of resveratrol and Coenzyme Q10 exclusively and in combination  to the four treatment groups for approximately three months, the remaining six groups (negative  and positive controls as well as four treatment groups) were terminated and differential leukocyte counts  once again determined. Eosinophil counts were significantly higher in the baseline termination group than  all other experimental groups assessed except for the negative control SWR/J mice, possessing normal  muscle and used in research as a general purpose strain. Eosinophil granules are suggested to reduce inflammation  caused by other leukocytes. At onset of dysferlinopathy between four and six weeks of age, the  increase in eosinophil counts could very likely be a compensation mechanism to decrease initial inflammation  in the muscular tissues of the dysferlinopathic mice. Neutrophil counts of the baseline termination  group were significantly higher only when compared to the resveratrol/Coenzyme Q10 combination group.  Neutrophils are linked to early inflammatory responses and often sensitised in self-antigen recognition  characteristic of autoimmune disease, a known complication in the SJL strain. Thus the higher neutrophil  count in the six week old mice is probably related to inflammation at disease onset, but may also be indicative  of autoimmunity; whereas the eosinophil counts may possibly play a more definitive role in the pathogenesis  of dysferlinopathy. Further morphological studies will serve to clarify the roles of these leukocytes  in dysferlinopathy.