The organelle dysfunction that occurs in neurons of individuals with multiple sclerosis (MS) may not be related to a symptomatic state, according to a study recently published in Neurobiology of Diseases.

“Data further our understanding of mechanisms related to experimental autoimmune encephalomyelitis progression and point to very early axonal mitochondrial dysfunction as central to the neuropathogenesis of MS evolution,” the authors wrote.

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This experimental study utilized MOG35-55-immunized NOD and PLP139-151-immunized SJL as models of progressive and relapsing-remitting experimental autoimmune encephalomyelitis, the investigators noted. All experimental animals were females. The researchers studied the spinal cord to identify a pattern of mitochondrial homeostasis and the symptomatic stage.

The immunologic cell infiltrate was comparable among both mice breeds, mostly consisting of T helper 1 (Th1) cells and neutrophils. Regardless, only the NOD group exhibited alterations in the mitochondrial homeostasis in the axon, lower mitochondrial DNA (mtDNA) and increased cristae, and several mitochondrial respiratory complex subunits such as Atp5d, Cox1, Nd2, and Sdha.

Moreover, the induction of 4 region genes that targeted mitochondriogenesis and 4 mitochondrial morphology occurred in the early stages after immunization in the lumbar spinal cord. Interestingly, such derangement was less notorious in the thoracic spinal cord.

Also, the researchers identified that the mitochondrial radical scavenger Mito-TEMPO did not influence the dysregulation of the transcriptome while conserving its ability to lower H2O2 content and decreasing cristate remodeling as well as mtDNA depletion.

“Lastly, the concomitant inability of Mito-TEMPO to restore expression of proteins involved in mitochondrial biogenesis and respiratory chain provides first hints of at least 2 independent signaling pathways participating to EDAM,” the authors highlighted.

These findings demonstrate that the interference with mitochondrial homeostasis seen in MS is not specifically related to a symptomatic state but are rather present during the asymptomatic period. Moreover, this organelle pattern was only observed among mouse models with progressive MS but not relapsing-remitting MS. Finally, scavenging oxygen radicals from the mitochondria could potentially lead to a partial recovery.


Buonvicino D, Ranieri G, Guasti D, et al. Early derangement of axonal mitochondria occurs in a mouse model of progressive but not relapsing-remitting multiple sclerosis. Neurbiol Dis. Published online January 23, 2023. doi:10.1016/j.nbd.2023.106015