4.7 Article

Imaging of α-Synuclein Aggregates in a Rat Model of Parkinson's Disease Using Raman Microspectroscopy

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.664365

Keywords

alpha-synuclein; Raman microspectroscopy; Parkinson's disease; brain; enteric nervous system

Funding

  1. EU Joint Programme Neurodegenerative Disease Research (JPND) [JPCOFUND_FP829-047 aSynProtect]
  2. Bundesministerium fur Bildung und Forschung (BMBF)
  3. Intramural Tubingen University Fortune grant fund [YS: 2642-00/F.1513281]
  4. Deutsche Forschungsgemeinschaft [INST 2388/64-1, EXC 2180-390900677]
  5. Ministry of Science, Research and the Arts of Baden-Wurttemberg [33-729.55-3/214, SI-BW 01222-91]
  6. State Ministry of Baden-Wurttemberg for Economic Affairs, Labour and Tourism
  7. Deutsche Forschungsgemeinschaft (DFG)
  8. University of Tubingen

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Parkinson's disease is characterized by the formation of Lewy bodies in the brain, containing aggregated alpha-Synuclein. Raman imaging technology can detect alpha-Synuclein aggregates in colon tissues, showing promise as a useful tool in PD pathology research.
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 alpha-Synuclein (alpha-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 alpha-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 alpha-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 alpha-Syn aggregates in colon tissues of a PD rat model and making it a promising tool for future use in PD pathology.

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