Fig. 5: Downregulation of dopamine pathway related genes in early synucleinopathy.
From: Transcriptomic profiling of early synucleinopathy in rats induced with preformed fibrils
a Diagram of the dopamine pathway and vesicle organization via synapsins and α-syn. Proteins encoded by transcripts downregulated in early synucleinopathy are highlighted in green. b Fischer 344 rats received two intrastriatal injections of 4 µg/µL α-syn PFFs or PBS (Vehicle), SN was collected 2-months after PFF administration from flash frozen tissue and processed for ddPCR. Graphs show mRNA from genes in the dopamine pathway normalized to Rpl13a mRNA and measured via ddPCR. Transcripts assessed were Th (tyrosine hydroxylase), Ddc (DOPA decarboxylase), Syn1 (synapsin 1), Syn2 (synapsin 2), Syn3 (synapsin 3), Slc18a2 (vesicular monoamine transporter 2 or VMAT2), Drd2 (dopamine receptor D2), Slc6a3 (dopamine transporter or DAT), Rgs8 (regulator of G protein signaling), Aldh1a1 (aldehyde dehydrogenase 1 family member A1), Snca (alpha-synuclein or α-syn), and Sncg (gamma-synuclein or γ-syn). Columns indicate the group means, circles represent individual data points (n = 8 per group before outlier removal), error bars represent ±1 standard error of the mean. An asterisk represents significance (p ≤ 0.05). Outliers were removed based on the absolute deviation from the median method. c Male Fischer 344 rats received two intrastriatal injections of 4 µg/µL α-syn PFFs, brains were removed 2-months after PFF administration and processed for fluorescent in situ hybridization (FISH). Panels show representative FISH micrographs from the SNpc dopamine pathway specific transcript Slc6a3. White box denotes the area of the higher magnification images, which show Slc6a3 mRNA (red) and immunofluorescent staining for pSyn (cyan). White arrows denote neurons containing pSyn inclusions which show a qualitative decrease in Slc6a3 mRNA.
