Abstract
A hallmark of Parkinson’s disease (PD) is the formation of Lewy bodies in the brain. Lewy bodies are rich in the aggregated form of misfolded α-Synuclein (α-Syn). The brain from PD patients can only be analyzed after postmortem, therefore, limiting the diagnosis of PD to the manifestation of motor symptoms. In PD patients and animal models, phosphorylated α-Syn was detected in the peripheral tissues including the gut, thus, raising the hypothesis that early-stage PD could be diagnosed based on colon tissue biopsies. Non-invasive marker-free technologies represent ideal methods to potentially detect aggregated α-Syn in vivo. Raman microspectroscopy has been established for the detection of molecular changes such as alterations of protein structures. Using Raman imaging and microspectroscopy, we analyzed the olfactory bulb in the brain and the muscularis mucosae of colon tissue sections of a human BAC-SNCA transgenic (TG) rat model. Raman images from TG and WT rats were investigated using principal component analysis (PCA) and true component analysis (TCA). Spectral components indicated protein aggregates (spheroidal oligomers) in the TG rat brain and in the colon tissues even at a young age but not in WT. In summary, we have demonstrated that Raman imaging is capable of detecting α-Syn aggregates in colon tissues of a PD rat model and making it a promising tool for future use in PD pathology.
Highlights
Parkinson’s disease (PD) is the second most common disorder among neurodegenerative diseases with 6.1 million persons afflicted worldwide as estimated in 2016 (Alves et al, 2008; Dorsey et al, 2018)
The α-Syn-stained area was used for measurement by Raman microspectroscopy on a separate brain slide (Supplementary Figure 1b)
In comparison between the 4M samples, signs of fibrillization were detected in the amide I region of TG 4M, where α-helix, βsheet and extended β-strand, and polyproline II (PPII) molecules were detected, indicating early spheroidal oligomers
Summary
Parkinson’s disease (PD) is the second most common disorder among neurodegenerative diseases with 6.1 million persons afflicted worldwide as estimated in 2016 (Alves et al, 2008; Dorsey et al, 2018) This disease burden is projected to have doubled in the past 25 years, whilst the number of older people did not increase in the same amount, indicating environmental factors could have an important role in PD progression (Dorsey et al, 2018). Phosphorylation is a usual characteristic as posttranslational phosphorylation of α-Syn is observed in 90% of misfolded proteins, while in cytosolic α-Syn, only 4% is phosphorylated (Kim et al, 2014). Even though α-Syn is an abundant protein in the brain, its exact function remains elusive in neuronal loss and their effective functions
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