Abstract #0267

Multimodal brain MRI characterization of a mouse model of Down syndrome and evaluation of a pharmacological treatment.

Julien CAILLETTE¹, Laëtitia Degiorgis¹, Marion Sourty¹, Marion Rame¹, Helin Atas-Ozcan², Laurent Meijer³, Yann Herault², and Laura-Adela Harsan^1,4

¹ICube, University of Strasbourg-CNRS, Strasbourg, France, ²IGBMC, University of Strasbourg-CNRS-INSERM, Illkirch-Graffenstaden, France, ³Perha Pharmaceuticals, Perharidy Peninsula, Roscoff, France, ⁴Department of Biophysics and Nuclear Medicine, University Hospital of Strasbourg, Strasbourg, France

Synopsis

DYRK1A protein-kinase overexpression was identified as key player in cognitive impairments observed in Down syndrome (DS) patients and in animal models. Inhibition of this kinase rescued cognitive deficits in the Dp1Yey mouse model of DS, but the associated mechanisms remain unknown. Here we used multimodal brain MRI and characterized the morphology, microstructure and functional connectivity (FC) of Dp1Yey mice. Voxel-based morphometry revealed brain-wide morphological alterations in Dp1Yey mice, while DTI analysis revealed white matter changes. Further, rsfMRI showed that pharmacologic DYRK1A inhibition modifies the functional connectivity for memory related nodes, synergistic with cognitive improvements observed in behavioral tests.

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