Tenascin-C deficiency ameliorates alzheimer's disease-related pathology in mice

Kan Xie, Yang Liu, Wenlin Hao, Silke Walter, Botond Penke, Tobias Hartmann, Melitta Schachner, Klaus Fassbender

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20 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposits of amyloid β peptide (Aβ) and microglia-driven inflammatory activation. Tenascin-C (tnc) is an extracellular matrix protein that is upregulated in inflammation and induces further inflammatory responses. We hypothesized that tnc contributes to the inflammatory pathology in AD. Using real-time polymerase chain reaction, we observed that tnc gene transcription was upregulated in cultured microglia after Aβ challenge and in the brain of an AD mouse model that overexpresses mutated amyloid precursor protein (APP) in neural cells. By cross-breeding APP-transgenic mice and tenascin-C-deficient mice, we demonstrated using real-time polymerase chain reaction, Western blot analysis, enzyme-linked immunosorbent assay, and immunohistochemistry that tnc deficiency reduces pro- but enhances anti-inflammatory activation in the mutated APP-transgenic mouse brain, associated with a reduced cerebral Aβ load and higher levels of the postsynaptic density protein 95. Thus, our study indicates that functional inhibition of tnc exerts beneficial effects on AD pathogenesis, suggesting a potential for tnc as a new therapeutic target in AD.

Original languageEnglish
Pages (from-to)2389-2398
Number of pages10
JournalNeurobiology of Aging
Volume34
Issue number10
DOIs
Publication statusPublished - Oct 1 2013

Keywords

  • Alzheimer's disease
  • Inflammation
  • Neurodegeneration
  • Tenascin-C

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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    Xie, K., Liu, Y., Hao, W., Walter, S., Penke, B., Hartmann, T., Schachner, M., & Fassbender, K. (2013). Tenascin-C deficiency ameliorates alzheimer's disease-related pathology in mice. Neurobiology of Aging, 34(10), 2389-2398. https://doi.org/10.1016/j.neurobiolaging.2013.04.013