Impaired SDF1/CXCR4 signaling in glial progenitors derived from SOD1 G93A mice

Yongquan Luo, Haipeng Xue, Andrea C. Pardo, Mark P. Mattson, Mahendra S. Rao, Nicholas J Maragakis

Research output: Contribution to journalArticle

Abstract

Mutations in the superoxide dismutase 1 (SOD1) gene are associated with familial amyotrophic lateral sclerosis (ALS), and the SOD1G93A transgenic mouse has been widely used as one animal model for studies of this neurodegenerative disorder. Recently, several reports have shown that abnormalities in neuronal development in other models of neurodegeneration occur much earlier than previously thought. To study the role of mutant SOD1 in glial progenitor biology, we immortalized glial restricted precursors (GRIPs) derived from mouse E11.5 neural tubes of wild-type and SOD1G93A mutant mice. Immunocytochemistry using cell lineage markers shows that these cell lines can be maintained as glial progenitors, because they continue to express A2B5, with very low levels of glial fibrillary acidic protein (astrocyte), βIII-tubulin (neuron), and undetected GalC (oligodendrocyte) markers. RT-PCR and immunoblot analyses indicate that the chemokine receptor CXCR4 is reduced in SOD1G93A GRIPs. Subsequently, SOD1G93A GRIPs are unable to respond to SDF1α to activate ERK1/2 enzymes and the transcription factor CREB. This may be one pathway leading to a reduction in SOD1G93A cell migration. These data indicate that the abnormalities in SOD1G93A glial progenitor expression of CXCR4 and its mediated signaling and function occur during spinal cord development and highlight nonneuronal (glial) abnormalities in this ALS model.

Original languageEnglish (US)
Pages (from-to)2422-2432
Number of pages11
JournalJournal of Neuroscience Research
Volume85
Issue number11
DOIs
StatePublished - Aug 15 2007

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Neuroglia
Neural Tube
Chemokine Receptors
Glial Fibrillary Acidic Protein
Oligodendroglia
Amyotrophic Lateral Sclerosis
Cell Lineage
Tubulin
Superoxide Dismutase-1
Astrocytes
Neurodegenerative Diseases
Transgenic Mice
Cell Movement
Spinal Cord
Transcription Factors
Animal Models
Immunohistochemistry
Neurons
Cell Line
Polymerase Chain Reaction

Keywords

  • Chemotaxis
  • ERK activation
  • Migration
  • Neural progenitors
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Impaired SDF1/CXCR4 signaling in glial progenitors derived from SOD1 G93A mice. / Luo, Yongquan; Xue, Haipeng; Pardo, Andrea C.; Mattson, Mark P.; Rao, Mahendra S.; Maragakis, Nicholas J.

In: Journal of Neuroscience Research, Vol. 85, No. 11, 15.08.2007, p. 2422-2432.

Research output: Contribution to journalArticle

Luo, Yongquan ; Xue, Haipeng ; Pardo, Andrea C. ; Mattson, Mark P. ; Rao, Mahendra S. ; Maragakis, Nicholas J. / Impaired SDF1/CXCR4 signaling in glial progenitors derived from SOD1 G93A mice. In: Journal of Neuroscience Research. 2007 ; Vol. 85, No. 11. pp. 2422-2432.
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