Apoptosis in oligodendrocytes is associated with axonal degeneration in P301L tau mice

Cindy Zehr, Jada Lewis, Eileen McGowan, Julia Crook, Wen Lang Lin, Kate Godwin, Joshua Knight, Dennis W. Dickson, Mike Hutton

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Transgenic mice overexpressing human tau with the P301L mutation develop neurofibrillary tangles, extensive gliosis, adult-onset motor abnormalities, and neuronal loss in affected brain regions. We investigated the mechanism of neuronal cell death in this model of tauopathy. There was no evidence of neuronal apoptosis at any age; however, a population of oligodendorocytes was immunopositive for TUNEL and activated caspase-3. EM confirmed that these oligodendrocytes were undergoing apoptosis. These data suggest that classical apoptosis is not a major mechanism of neuronal cell death associated with the tau dysfunction in this mouse model; however, prominent white matter pathology in the spinal cord suggests that axonal degeneration in dying neurons causes oligodendrocytes to undergo apoptosis. It is unknown if loss of oligodendrocytes either through apoptosis or through the formation of intracellular tau lesions further contributes to the neurodegeneration seen in these mice.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalNeurobiology of Disease
Volume15
Issue number3
DOIs
StatePublished - Apr 1 2004

Keywords

  • Alzheimer's disease
  • Caspase-3
  • Cell death
  • Frontotemporal dementia with parkinsonism linked to chromosome-17
  • TUNEL
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Neurology

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    Zehr, C., Lewis, J., McGowan, E., Crook, J., Lin, W. L., Godwin, K., Knight, J., Dickson, D. W., & Hutton, M. (2004). Apoptosis in oligodendrocytes is associated with axonal degeneration in P301L tau mice. Neurobiology of Disease, 15(3), 553-562. https://doi.org/10.1016/j.nbd.2003.12.011