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Fig. 7 | Acta Neuropathologica Communications

Fig. 7

From: Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein

Fig. 7

UPS impairment in nigral dopaminergic neurons is associated with perinuclear accumulation of phosphorylated α-synuclein species. Adult wild-type rats received unilateral stereotaxic co-injection of AAV-UbG76V-GFP with AAV-A53T or AAV-Empty into the right SNpc. Animals were culled at 1 wpi. a-b Immunofluorescent staining with anti-tyrosine hydroxylase (TH; cyan), anti-GFP (GFP; green) and either (a) anti-α-synuclein (SYN; red) or (b) anti-pS129 α-synuclein (SYNpS129; red) antibodies in SNpc at 1 wpi of AAV-A53T/AAV-UbG76V-GFP or AAV-Empty/AAV-UbG76V-GFP. Scale bars 20 μm. c Quantification of mean total α-synuclein and mean pS129 α-synuclein staining intensities in TH-labelled neurons classified as UbG76V-GFP or UbG76V-GFP+ in ipsilateral SNpc 1wpi of AAV-A53T/AAV-UbG76V-GFP. Dopaminergic neurons with elevated levels of UbG76V-GFP indicative of UPS dysfunction have elevated levels of phosphorylated α-synuclein species, independent of a significant change in total α-synuclein levels. Data are mean +/− SEM (*p < 0.05; two-tailed Student’s t test; n = 3 per group). d Representative high magnification image of TH-labelled neuron with elevated levels of UbG76V-GFP reporter reveals presence of punctate pS129 α-synuclein staining. Punctate pS129 α-synuclein staining is not observed in neighbouring TH-labelled neuron with basal UbG76V-GFP levels. Scale bar 5 μm. e Orthogonal z-stack view of the UbG76V-GFP+ TH-labelled neuron shown in (d) with anti-pS129 α-synuclein staining (SYNpS129; red) and DAPI nuclear counterstain shown. Puncta of phosphorylated α-synuclein species have a perinuclear location

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