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Tau signaling in injured spinal cord
Thesis   Open access

Tau signaling in injured spinal cord

Natasha Bukreska
Master of Science (M.S.), Drexel University
Apr 2026
DOI:
https://doi.org/10.17918/00011345
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Abstract

Big tau C2 hemisections Dorsal root ganglia Phosphorylated tau Spinal cord injuries Tau proteins
Tau is a microtubule-associated protein that plays a critical role in maintaining axonal structure and regulating cytoskeletal dynamics, with its phosphorylation state tightly linked to neuronal stability and degeneration. While tau pathology has been extensively studied in neurodegenerative diseases and traumatic brain injury, its role in spinal cord injury (SCI) remains incompletely understood. This study investigates tau isoform expression and phosphorylation in the cervical spinal cord following a high lateral C2 hemisection (C2Hx) in adult female rats. To assess injury-induced molecular changes, Western blot analysis was performed on spinal cord tissue collected caudal to the lesion at 4 weeks post-injury. Quantification of low-molecular-weight (LMW) tau and high-molecular-weight Big tau revealed no significant differences between injury and control groups, indicating that overall tau protein abundance remains relatively stable during the early chronic phase. In contrast, phosphorylated tau (p-tau), detected by using the AT8 antibody, was significantly elevated in injured animals, suggesting a shift in tau functional state rather than protein level. Additionally, assessment of markers of microtubule stability and dynamics revealed increased acetylated tubulin and decreased tyrosinated tubulin following injury, indicating a shift toward a more stable but less dynamic cytoskeletal environment. To further examine spatial distribution, immunohistochemistry was conducted on spinal cord sections at 6 weeks post-injury and dorsal root ganglia (DRG) at 8 weeks post-injury. These analyses demonstrated increased p-tau immunoreactivity within the ipsilateral dorsal horn regions of the spinal cord and the DRG in injured animals compared to controls. Together, these findings demonstrate that cervical SCI induces persistent tau phosphorylation without altering total tau levels, and that this modification extends beyond the lesion site into distal spinal regions and beyond the acute phase of injury. This dysregulation may contribute to maladaptive structural remodeling and impaired plasticity in the injured spinal cord.

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