Abstract
The abundant axonal microtubule-associated protein tau regulates microtubule and actin dynamics, thereby contributing to normal neuronal function. We examined whether mice deficient in tau (Tau -/-) or with high levels of human tau differ from wild-type (WT) mice in their susceptibility to neuroaxonal injury in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. After sensitization with MOG 35-55, there was no difference in clinical disease course between human tau and WT mice, but Tau -/- mice had more severe clinical disease and significantly more axonal damage in spinal cord white matter than those in WT mice. Axonal damage in gray matter correlated with clinical severity in individual mice. By immunoblot analysis, the early microtubule-associated protein-1b was increased 2-fold in the spinal cords of Tau -/- mice with chronic experimental autoimmune encephalomyelitis versus naive Tau -/- mice. This difference was not detected in comparable WT animals, which suggests that there was compensation for the loss of tau in the deficient mice. In addition, levels of the growth arrest-specific protein 7b, a tau-binding protein that is stabilized when bound to tau, were higher in WT than those in Tau -/-spinal cord samples. These data indicate that loss of tau exacerbates experimental autoimmune encephalomyelitis and suggest that maintaining tau integrity might reduce the axonal damage that occurs in inflammatory neurodegenerative diseases such as multiple sclerosis.
Original language | English (US) |
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Pages (from-to) | 422-433 |
Number of pages | 12 |
Journal | Journal of Neuropathology and Experimental Neurology |
Volume | 71 |
Issue number | 5 |
DOIs | |
State | Published - May 2012 |
Keywords
- Axonal damage
- Experimental autoimmune encephalomyelitis
- Growth arrestYspecific protein 7b
- Microtubuleassociated protein 1b
- Multiple sclerosis
- Myelin oligodendrocyte glycoprotein (MOG)
- Tau
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience