Structural MRI Reveals Cervical Spinal Cord Atrophy in the P301L Mouse Model of Tauopathy: Gender and Transgene-Dosing Effects

Abstract

In primary tauopathies, the deposition of tau neurofibrillary tangles and threads as well as neurodegenerative changes have been found within the brain and spinal cord. While degenerative changes have been intensively studied in the brain using structural magnetic resonance imaging (MRI), MRI studies investigating the spinal cord are still scarce. In the present study, we acquired ex vivo high resolution structural MRI of the cervical spinal cord of 8.5–9 month old hemizygous and homozygous P301L mice and non-transgenic littermates of both genders. We assessed the total cross-sectional area, and the gray and white matter anterior-posterior width and left-right width that are established imaging marker of spinal cord degeneration. We observed significant tissue-specific reductions in these parameters in female P301L mice that were stronger in homozygous than in hemizygous P301L mice, indicating both an effect of gender and transgene expression on cervical spinal cord atrophy. Moreover, atrophy was stronger in the gray matter than in the white matter. Immunohistochemical analysis revealed neurodegenerative and neuroinflammatory changes in the cervical spinal cord in both the gray and white matter of P301L mice. Collectively, our results provide evidence for cervical spinal cord atrophy that may directly contribute to the motor signs associated with tauopathy.