Characterisation of spinal cord in a mouse model of spastic paraplegia related to abnormal axono–myelin interactions by in vivo quantitative MRI

Abstract

In inherited neurodegenerative disorders the engineering of genetically modified mice for the causative genes have provided new insights in the understanding of axono–glial interactions. Patients lacking the major proteins of the central nervous system myelin, the proteolipoproteins (PLP1) exhibit an ascending axonopathy, named spastic paraplegia type 2. Our objective was to examine the interest of using quantitative MRI for non invasive detection of spinal cord (SC) consequences of the PLP1 defect in a mouse model of SPG2 (PLP1−/Y). For this purpose an MRI acquisition and retrospective correction chain was set up to map apparent diffusion coefficients (ADC) and T2 in the mouse cervical SC which improve the intra- and inter-animal homogeneity. This reliable imaging processing protocol allowed to detect significant changes between PLP1−/Y and wild type 15-month old SC, mainly no longer detected ex vivo after SC fixation. On the basis of ADC // and ADC ⊥ variations, white matter (WM) damages were characterised on both the myelin and axonal components. The microstructural changes observed in the Plp1 deficient grey matter (GM) were concomitantly related to the isotropic increase of GM ADC. The T2 reduction measured in the WM as well as the GM of the mutant SC seems to be also an interesting marker of the SC axono–glial dysfunction. The present study demonstrated the interest of quantitative MRI for phenotyping in vivo the WM and GM changes in SC neurodegenerative disorders related to myelin and impaired glia–axonal interaction.