Friedreich ataxia (FA) causes a complex clinical and neuropathological phenotype. Dorsal root ganglia (DRG) are a primary target of the disease. Traditional interpretation of the DRG lesion includes atrophy of large neurons, proliferation of satellite cells, and formation of residual nodules. A systematic immunohistochemical and immunofluorescence study of DRG in 15 FA cases and 12 controls, however, supports the conclusion that frataxin deficiency in FA primarily affects satellite cells, and that loss of ganglion cells is due to failing trophic support and inflammatory infiltration.

A panel of antibodies was used to reveal the cytoplasm of satellite cells (S100α, glutamine synthase, excitatory amino acid transmitter 1, glial fibrillary acidic protein), the inward-rectifying potassium channel (Kir4.1), gap junctions (connexin 43), basement membranes (laminin-2), mitochondria (ATP synthase β-subunit [ATP5B] and frataxin), and monocytes (CD68, CD14, and IBA1). Reaction product of the cytoplasmic markers and laminin-2 confirmed proliferation of satellite cells into multiple perineuronal layers and residual nodules. Connexin 43-reactive gap junctions were greatly increased. The additional satellite cells displayed enhanced mitochondrial ATP5B but lacked frataxin fluorescence. DRG monocytes in FA cases were more abundant than normal, separated satellite cells from neurons, and participated in the formation of residual nodules. (Supported by NIH R01NS069454 and Friedreich's Ataxia Research Alliance).

Conflictsof Interest:

None.