Aggregation of α-synuclein in specific brain areas. (A-G) Rostrocaudal distribution of α-synuclein in Smad3 wild-tupe and deficient mice. Red points represent positive α-synuclein staining in wild-type and null mutant. Blue asterisks illustrate cellular and neuritic aggregates present in old heterozygous and young Smad3 null mice. (H-Q) Photomicrography showing α-synuclein positive structures. (H-J) ST striatum, (K) M1 primary motor cortes, cc corpus callosum in Smad3-/-, (L-N) SN substantia nigra, (O) cp cerebral peduncle, (P) ll lateral lemniscus, and (Q) fa, anterior funiculus of the spinal cord. The double arrows show positive fibres detected in Smad3 deficient mice, asterisks point to synaptic terminals with a punctuate morphology, and the arrowheads indicate perykarial inclusions. (R) Confocal microscopic images of TH/α-synuclein/Dapi triple labelling in the SN of Smad3+/+ and Smad3-/- mice. In control tissues, α-synuclein is present in the cytoplasm of dopaminergic neurons. The aggregates observed in Smad3 deficiency are double-labelled for both molecules (arrow). The window is further magnified to get a better appraisal of the accumulation of α-synuclein in a TH(+) neuron.