Diversity of Mitochondrial Pathology in a Mouse Model of Axonal Degeneration in Synucleinopathies
Axonal swellings in two types of synucleinopathy model mice. Immunoelectron microscopic analysis was performed using anti-αS. αS-immunopositive globules (a) were characterized by lysosomal pathologies such as myelinosomes (in αS mice) and lipid droplets (in P123H βS mice). Accumulation of mitochondria was occasionally observed only in αS mice (a: blue). Because P123H βS-immunopositive globules in brains of P123H βS tg mice were immunopositive for αS (~100%), double immunofluorescence analyses of αS tg mice (b: nine left panels) and P123H βS tg mice (b: nine right panels) were performed using αS as a globule identification. In αS tg mice, cytochrome c (b: upper panels) showed punctate patterns, while VDAC1 (b: middle panels) was located diffusely. In P123H βS tg mice, cytochrome c and VDAC1 were all immunonegative. Note that αS-globules were immunopositive for LRRK2 (b: lower panels), whereas P123H βS globules were negative for LRRK2. Quantification of data for phosphorylation of αS, nitration of αS, and lipid oxidation (immunoreactivity for 4-hydroxy-2-nonenal) in the αS-globules of both of synucleinopathy model mice (c). Scale bar = 1 μm for (a); 5 µm for (b). Please see  Mol. Brain for detailed information; (reprinted from Mol. Brain, Sekigawa et al., 5 : 34 with permission).
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