engleski

MRI reveals structural changes in white matter of GD3 synthase-deficient mice

We investigated whether ex vivo magnetic resonance imaging (MRI) signal is affected by altered membrane (glycosphingo)lipid composition in GD3 synthase deficient (St8sia1 knock-out, KO) mice. 19 adult (10 St8sia1 KO and 9 age matched wild- type, WT) male mice were perfused with 4% paraformaldehyde, their heads rehydrated in PBS with 0.05% sodium azide for 1 to 3 months and scanned using a 9.4T Bruker Biospec® MR scanner to acquire T2-weighted images, diffusion tensor imaging (DTI) data, and T1 relaxation maps. After imaging, selected histological and immunohistochemical markers were analysed in brain tissue sections. The lack of GD3 synthase caused global and widespread changes in MR signal. Interestingly, St8sia1 KO brains were larger overall, but there were also distinct regional volume differences, with increases in the hippocampus, brain stem, cerebellum and nucleus accumbens, and decreases in cortical and thalamic regions. T1 relaxation time was decreased in St8sia1 KO mice in many areas but the overall pattern did not match regional volume changes. Analysis of DTI showed an overall increase in mean, axial and radial diffusivity whereas fractional anisotropy (FA) increased in the corpus callosum and decreased in hypothalamus and inferior colliculi. Preliminary histological analysis indicated morphological differences in the white matter of St8sia1 KO brains, in the same areas demonstrating changed MRI. Observed changes in MRI signal which accompany altered membrane ganglioside pattern, particularly when DTI components are analysed, suggest that MRI is suitable for detection of structural changes in white matter caused by disruption of membrane lipid composition.

gangliosides ; glycosphingolipids ; St8sia1

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