Adult glial precursor proliferation in mutant SOD1G93A mice

Tim Magnus, Jessica Carmen, Jessica Deleon, Haipeng Xue, Andrea C. Pardo, Angelo C. Lepore, Mark P. Mattson, Mahendra S. Rao, Nicholas J. Maragakis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The focus of most neurodegenerative disease studies has been on neuronal death in particular subpopulations of the central nervous system. The associated response of glial populations has been ascribed the term "reactive astrocytosis." This has been defined as the proliferation of astrocytes accompanied by cellular hypertrophy and changes in gene expression following injury to the central nervous system. Yet the significance of that response to disease course is debated. In both human ALS and in the SOD1G93A mouse model of ALS, reactive astrocytosis is a hallmark of the disease - particularly at endstage. The brain also harbors immature progenitors which have the capacity for differentiation into both glial and neuronal lineages. We examined whether glial progenitors in the adult spinal cord of SOD1 G93A mice become activated and contribute the astroglial response observed in this model. We found that the glial progenitor proteoglycan NG2 is increased in parallel with GFAP during the symptomatic phase of the disease and that there is a differential in vitro response of SOD1G93A glial progenitors to inflammatory cytokines when compared to wildtype mouse glial progenitors. This response was accompanied by the proliferation of glial progenitors but not mature GFAP+ astrocytes, through the translocation of the transcription factor Olig2 from the nucleus to the cytoplasm - resulting in astrocyte differentiation. These data suggest that adult glial progenitors from SOD1G93A mice differentially respond to inflammatory cytokines and contribute to the observed reactive astrocytosis observed in SOD1G93A mouse lumbar spinal cord.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalGlia
Volume56
Issue number2
DOIs
StatePublished - Jan 15 2008

Keywords

  • ALS
  • Astrocytosis
  • Progenitors
  • Reactive astrocyte

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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