Astroglial transcriptome dysregulation in early disease of an ALS mutant SOD1 mouse model

Sean J. Miller, Ping Wu Zhang, Jenna Glatzer, Jeffrey D. Rothstein

Research output: Contribution to journalArticlepeer-review


Astroglia are a morphologically diverse and highly abundant cell type in the CNS. Despite these obvious observations, astroglia still remain largely uncharacterized at the cellular and molecular level. In disease contexts such as amyotrophic lateral sclerosis (ALS), it has been widely shown that astroglia downregulate crucial physiological functions, become hypertrophied, reactive, and toxic to motor neurons. However, little is known about the astroglia-specific transcriptomic changes that occur during ALS disease progression, especially early in disease. To address this, we FACS-isolated pure astroglia from early and mid-symptomatic superoxide dismutase 1 (SOD1) G93A spinal cord and performed microarray sequencing, in hopes to uncover markers and pathways driving astroglia dysfunction in ALS. After extensive analyses, we uncovered genes selectively enriched and downregulated in both control and SOD1 astroglia at both disease points. In addition, we were able to identify genes and pathways differentially expressed that may have relevance with other neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease, suggesting a common theme among astroglial dysfunction in neurodegenerative disease. In aggregate, this study sheds light on the common and unique themes of dysfunction that astroglia undergo during neurodegenerative disease progression and provides candidate targets for therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)37-48
Number of pages12
JournalJournal of Neurogenetics
Issue number1-2
StatePublished - Apr 3 2017


  • ALS
  • SOD1
  • astroglia dysfunction
  • neurodegeneration
  • transcriptome

ASJC Scopus subject areas

  • Genetics
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Astroglial transcriptome dysregulation in early disease of an ALS mutant SOD1 mouse model'. Together they form a unique fingerprint.

Cite this