Spinal cord perfusion impairments in the M83 mouse model of Parkinson's disease

Benjamin Francois Combes, Sandeep Kumar Kalva, Pierre-Louis Benveniste, Agathe Tournant, Man Hoi Law, Joshua Newton, Maik Krueger,Rebecca Z. Weber,Ines Dias,Daniela Noain,Xose Luis Dean Ben,Uwe Konietzko,Christian R. Baumann,Per-Goran Gillberg,Christoph Hock,Roger M. Nitsch,Julien Cohen-Adad,Daniel Razansky,Ruiqing Ni

crossref(2024)

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摘要
Metabolism and bioenergetics in the central nervous system play important roles in the pathophysiology of Parkinson's disease (PD). Here, we employed a multimodal imaging approach to assess oxygenation changes in the spinal cord of a transgenic M83 murine model of PD in comparison to non-transgenic littermates at 9-12 months-of-age. A lower oxygen saturation (SO2)SVOT was detected in vivo with spiral volumetric optoacoustic tomography (SVOT) in the spinal cord of M83 mice compared to non-transgenic littermate mice. Ex-vivo high-field T1-weighted magnetic resonance imaging (MRI) and immunostaining for alpha-synuclein (phospho-S129) and vascular organisation (CD31 and GLUT1) were used to investigate the nature of the abnormalities detected via in vivo imaging. Ex-vivo analysis showed that the vascular network in the spinal cord was not impaired in the spinal cord of M83 mice. Ex-vivo MRI assisted with deep learning-based automatic segmentation showed no volumetric atrophy in the spinal cord of M83 mice compared to non-transgenic littermates, whereas nuclear alpha-synuclein phosphorylated at Ser129 site could be linked to early pathology and metabolic dysfunction. The proposed and validated non-invasive high-resolution imaging tool to study oxygen saturation in the spinal cord of PD mice holds promise for assessing early changes preceding motor deficits in PD mice.
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