Mitochondria again, but this time in muscle!

Pathol Res Pract. 2015 Feb 17. pii: S0344-0338(15)00027-8. doi: 10.1016/j.prp.2015.02.004. [Epub ahead of print]

Skeletal muscle findings in experimental autoimmune encephalomyelitis.

Luque E, Ruz-Caracuel I, Medina FJ, Leiva-Cepas F, Agüera E, Sánchez-López F, Lillo R, Aguilar-Luque M, Jimena I, Túnez I, Peña J.

INTRODUCTION:Skeletal muscle is a target organ in multiple sclerosis, a chronic debilitating disease of the central nervous system caused by demyelination and axonal deterioration. Since the experimental autoimmune encephalomyelitis model reproduces the relapsing-remitting course found in most multiple sclerosis patients, this model was used to compare the histological features of skeletal muscle at onset with those observed at the start of the second relapse.

MATERIAL AND METHODS:Histological, histochemical and ultrastructural changes, as well as biochemical oxidative damage and antioxidant-system markers, were examined in the soleus and extensor digitorum longus muscles of Dark Agouti rats in which experimental autoimmune encephalomyelitis had been induced by active immunization using myelin oligodendrocyte glycoprotein.
RESULTS:Histological examination at disease onset revealed ragged-red fibers and ultrastructural evidence of mitochondrial degeneration. At the second relapse, neurogenic changes included a wide range of cytoarchitectural lesions, skeletal muscle atrophy and the appearance of intermediate fibers; however, differences were observed between soleus and extensor digitorum longus lesions. Biochemical tests disclosed an increase in oxidative stress markers at onset, which was more pronounced at the second relapse.
CONCLUSIONS:Microscopic findings suggest that two patterns can be distinguished at disease onset: an initial phase characterized by muscle mitochondrial alterations, and a second phase dominated by a histological muscle pattern of clearly neurogenic origin.

 Structure of a skeletal muscle

This is work done in the mouse model of MS (the EAE model), and some caution should be exercised when drawing parallels with humans and with MS as a whole. 

Nonetheless, these findings raise interesting questions about whether the same happens in MSers? I've sometimes wandered about this in clinic, particularly in those with disproportionate muscle wasting, in so far as to send some of them to a neurophysiologist for EMGs! [In general terms were are taught that muscle wasting is a late feature of CNS disorders but seen early in peripheral nervous system disorders, including muscle disease].

But the researchers here demonstrate three fundamental facts: 1) That the muscle is affected in the acute phase i.e. onset of the EAE disease - equivalent to a human relapse, and the changes that take place are almost exclusively related to mitochondrial dysfunction; 2) it's only at the mid-to-longterm disease phase that the muscle changes point to changes that are neurogenic in origin, i.e. caused by denervation of the muscle (from lack of axons); and 3) mitochondrial damage is linked to an increase in oxygen reactive species production (i.e. oxidative stress), which is driving force for destruction of the denervated skeletal muscle over the long-term.

Electron micrograph of the periphery of a muscle (fibers are visible to the left of the image) showing clumped mitochondria (round things) displaying degenerative changes.

Could Co-enzyme Q10 supplementation therefore become a future addition to the steroid armamentarium in an MS relapse??

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