Neurobiology of Disease (Jul 2023)

A mitochondrial-targeted antioxidant (MitoQ) improves motor coordination and reduces Purkinje cell death in a mouse model of ARSACS

  • Brenda Toscano Márquez,
  • Tsz Chui Sophia Leung,
  • Jeanette Hui,
  • François Charron,
  • R. Anne McKinney,
  • Alanna J. Watt

Journal volume & issue
Vol. 183
p. 106157

Abstract

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Mitochondrial deficits have been observed in animal models of Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and in patient-derived fibroblasts. We investigated whether mitochondrial function could be restored in Sacs−/− mice, a mouse model of ARSACS, using the mitochondrial-targeted antioxidant ubiquinone MitoQ. After 10weeks of chronic MitoQ administration in drinking water, we partially reversed motor coordination deficits in Sacs−/− mice but did not affect litter-matched wild-type control mice. MitoQ administration led to a restoration of superoxide dismutase 2 (SOD2) in cerebellar Purkinje cell somata without altering Purkinje cell firing deficits. Purkinje cells in anterior vermis of Sacs−/− mice normally undergo cell death in ARSACS; however, Purkinje cells numbers were elevated after chronic MitoQ treatment. Furthermore, Purkinje cell innervation of target neurons in the cerebellar nuclei of Sacs−/− mice was also partially restored with MitoQ treatment. Our data suggest that MitoQ is a potential therapeutic treatment for ARSACS and that it improves motor coordination via increasing cerebellar Purkinje cell mitochondria function and reducing Purkinje cell death.

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