Quantitative susceptibility mapping depicts severe myelin deficit and iron deposition in a transgenic model of multiple system atrophy

Lambrecht V, Hanspach J, Hoffmann A, Seyler L, Mennecke A, Straub S, Marxreiter F, Bäuerle T, Winkler J, Laun FB (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Experimental Neurology Elsevier

Book Volume: 329

Article Number: 113314

DOI: 10.1016/j.expneurol.2020.113314

Abstract

Despite internationally established diagnostic criteria, multiple system atrophy (MSA) is frequently misdiagnosed, particularly at disease onset. While neuropathological changes such as demyelination and iron deposition are typically detected in MSA, these structural hallmarks were so far only demonstrated post-mortem. Here, we examine whether myelin deficit observed in a transgenic murine model of MSA can be visualized and quantified in vivo using specific magnetic resonance imaging (MRI) approaches. Reduced myelin content was measured histologically in prototypical white matter as well as mixed grey-white matter regions i.e. corpus callosum, anterior commissure, and striatum of transgenic mice overexpressing human α-synuclein under the control of the myelin basic protein promotor (MBP29-hα-syn mice). Correspondingly, in vivo quantitative susceptibility mapping (QSM) showed a strongly reduced susceptibility contrast in white matter regions and T2-weighted MR imaging revealed a significantly reduced grey-white matter contrast in MBP29-hα-syn mice. In addition, morphological analysis suggested a pronounced, white matter-specific deposition of iron in MBP29-hα-syn mice. Importantly, in vivo MRI results were matched by comprehensive structural characterization of myelin, iron, and axonal directionality. Taken together, our results provide strong evidence that QSM is a very sensitive tool measuring changes in myelin density in conjunction with iron deposition in MBP29-hα-syn mice. This multimodal neuroimaging approach may pave the way towards a novel non-invasive technique to detect crucial neuropathological changes specifically associated with MSA.

Authors with CRIS profile

Jannis Hanspach Professur für quantitative MR-Bildgebung (Heisenberg-Professur) Alana Hoffmann Department of Molecular Neurology Angelika Mennecke Department of Neuroradiology Franz Marxreiter Department of Molecular Neurology Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Jürgen Winkler Professur für Molekulare Neurologie Frederik Bernd Laun Professur für quantitative MR-Bildgebung (Heisenberg-Professur)

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE)

How to cite

APA:

Lambrecht, V., Hanspach, J., Hoffmann, A., Seyler, L., Mennecke, A., Straub, S.,... Laun, F.B. (2020). Quantitative susceptibility mapping depicts severe myelin deficit and iron deposition in a transgenic model of multiple system atrophy. Experimental Neurology, 329. https://doi.org/10.1016/j.expneurol.2020.113314

MLA:

Lambrecht, Vera, et al. "Quantitative susceptibility mapping depicts severe myelin deficit and iron deposition in a transgenic model of multiple system atrophy." Experimental Neurology 329 (2020).

BibTeX: Download