Structural interhemispheric connectivity defects in mouse models of BBSOAS: Insights from high spatial resolution 3D white matter tractography

In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3D-DTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.PMID:38408685 | DOI:10.1016/j.nbd.2024.106455
Source: Neurobiology of Disease - Category: Neurology Authors: Source Type: research