SATELLITE GLIAL RESPONSES IN FRIEDREICH’S ATAXIA

Friedreich ataxia (FA) is a rare neurodegenerative disorder characterized by early pathological alterations in the peripheral dorsal root ganglia (DRG), leading to progressive loss of sensory proprioceptive neurons, ganglionopathy, and severe proprioceptive deficits. FA is caused by mutations in the frataxin gene, resulting in reduced expression of frataxin, an essential ubiquitously expressed mitochondrial protein. While most studies have focused on the vulnerability of proprioceptive neurons, increasing evidence indicates that satellite glial cells (SGCs)—glial cells that tightly ensheath proprioceptor somata—exhibit reactivity in FA. This suggests that SGC dysfunction may play a critical role in proprioceptor dysfunction and degeneration. However, the contribution of DRG SGC reactivity to the FA phenotype remains poorly understood. Using a mouse model of FA combined with ultrastructural analysis by electron microscopy, we identified multiple alterations in SGC morphology and intracellular alterations, suggesting stress responses. These ultrastructural changes may represent novel cellular biomarkers of FA progression and provide new insight into glia-mediated mechanisms underlying sensory neuron degeneration.