Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo
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Date
2024-11
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Journal Article
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Abstract
Abnormal alpha-synuclein (alpha Syn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize alpha Syn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x-ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of alpha Syn inclusions and iron deposition. THK-565 showed increased fluorescence upon binding to recombinant alpha Syn fibrils and alpha Syn inclusions in post-mortem brain slices from patients with PD and M83 mice. Administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 min post-intravenous injection by wide-field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of alpha Syn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.
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34 (6)
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Wiley-Blackwell
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Subject
alpha-synuclein; fluorescence imaging; iron; magnetic resonance imaging; optoacoustic imaging; Parkinson's disease; susceptibility weighted imaging
Organisational unit
09648 - Razansky, Daniel / Razansky, Daniel
03782 - Riek, Roland / Riek, Roland
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Is new version of: https://doi.org/10.3929/ethz-b-000650938