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

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. ### Competing Interest Statement CH and RMN are employees and share-holders of Neurimmune AG, Schlieren, Switzerland. * CD31 : Cluster of differentiation 31 CSA : Cross-sectional areas DAPI : 4’,6-diamidino-2-phenylindole GLUT1 : Glucose transporter 1 GM : Grey matter HbO : Oxygenated hemoglobin HbR : deoxygenated hemoglobin MRI : Magnetic resonance imaging NTL : Non-transgenic littermate PD : Parkinson’s disease pS129-α-syn : Phospho-α-syn (p-α-syn) at Ser129 site sO2 : Oxygen saturation SVOT : Spiral volumetric optoacoustic tomography T1w : T1-weighted WM : White matter α-syn : Alpha-synuclein