Abstract
Background: In vivo diffusion tensor imaging (DTI) of the mouse brain was used to identify TDP-43 associated alterations in a mouse model for amyotrophic lateral sclerosis (ALS). Methods: Ten mice with TDP-43 G298S overexpression under control of the Thy1.2 promoter and 10 wild type (wt) underwent longitudinal DTI scans at 11.7 T, including one baseline and one follow-up scan with an interval of about 5 months. Whole brain-based spatial statistics (WBSS) of DTI-based parameter maps was used to identify longitudinal alterations of TDP-43 G298S mice compared to wt at the cohort level. Results were supplemented by tractwise fractional anisotropy statistics (TFAS) and histological evaluation of motor cortex for signs of neuronal loss. Results: Alterations at the cohort level in TDP-43 G298S mice were observed cross-sectionally and longitudinally in motor areas M1/M2 and in transcallosal fibers but not in the corticospinal tract. Neuronal loss in layer V of motor cortex was detected in TDP-43 G298S at the later (but not at the earlier) timepoint compared to wt. Conclusion: DTI mapping of TDP-43 G298S mice demonstrated progression in motor areas M1/M2. WBSS and TFAS are useful techniques to localize TDP-43 G298S associated alterations over time in this ALS mouse model, as a biological marker.
Original language | English (US) |
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Article number | 27 |
Journal | Translational Neurodegeneration |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - Aug 30 2019 |
Keywords
- Amyotrophic lateral sclerosis
- Diffusion tensor imaging
- Fiber tracking
- Mouse brain
- Mutant TDP-43
ASJC Scopus subject areas
- Clinical Neurology
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience