Early activation of microglia and astrocytes in mouse models of spinocerebellar ataxia type 1

M. Cvetanovic*, M. Ingram, H. Orr, P. Opal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Spinocerebellar ataxia type 1 (SCA1) is an incurable, dominantly inherited neurodegenerative disease of the cerebellum caused by a polyglutamine-repeat expansion in the protein ataxin-1 (ATXN1). While analysis of human autopsy material indicates significant glial pathology in SCA1, previous research has focused on characterizing neuronal dysfunction. In this study, we characterized astrocytic and microglial response in SCA1 using a comprehensive array of mouse models. We have discovered that astrocytes and microglia are activated very early in SCA1 pathogenesis even when mutant ATXN1 expression was limited to Purkinje neurons. Glial activation occurred in the absence of neuronal death, suggesting that glial activation results from signals emanating from dysfunctional neurons. Finally, in all different models examined glial activation closely correlated with disease progression, supporting the development of glial-based biomarkers to follow disease progression.

Original languageEnglish (US)
Pages (from-to)289-299
Number of pages11
JournalNeuroscience
Volume289
DOIs
StatePublished - Mar 9 2015

Keywords

  • Astrocytes
  • Glia
  • Microglia
  • Neurodegeneration
  • SCA1
  • Spinocerebellar ataxia type 1

ASJC Scopus subject areas

  • Neuroscience(all)

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