Fig. 1

Synuclein neuropathology in the MSA mice. a Confocal images of immunofliorescence for human α-syn, detected with 15G7 antibody (green), and p25α (oligodendroglial marker, red), demonstrate the oligodendrocytic localization of α-syn. Human α-syn staining in oligodendrocytes is represented not only as diffuse cytoplasmic signal (due to the transgenic overexpression) but more commonly by dot-like-profiles that fuse into larger GCI-like aggregates in the cytoplasm of oligodendrocytes of the PLP-α-syn mice. These dense structures can be observed also by conventional light microscopy and immunohistochemistry applying antibodies specific for pathological α-syn species: (b) 5G4 anti-human α-syn oligomers, and (c) anti-phosphorylated S129 α- syn (human and mouse) antibodies demonstrate the morphology of GCIs in the oligodendrocytic cytoplasm (arrowheads) or within the myelin sheaths (arrows). Apart from the presence of human α-syn in the oligodendrocytes and myelin sheaths, we were able by confocal microscopy to identify single dot-like profiles (arrow) in microglial cells (d) and neurons (e), however no fusion of these profiles into larger aggregates was seen in microglia or neurons as compared to oligodendroglia, suggesting an effective degradation of the human α-syn uptaken from the extracellular space into these cells. f Microphotographs show a wide-spread distribution of α-syn GCI-like aggregates detected by the above mentioned antibodies in various brain areas (dense profiles indicated with arrows), always visible in the PLP-α-syn mice, but not in the wildtype controls. Abbreviations: ci, capsula interna; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; pn, pontine nuclei; gl, granular layer; ml, molecular layer; cwm, cerebellar white matter; io, inferior olives. Scale bars, if not otherwise indicated, 5 μm