Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

Clare Wilhelm, Joel G. Hashimoto, Melissa L. Roberts, Shelley H. Bloom, Melissa R. Andrew, Kristine Wiren

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Chronic alcohol abuse is associated with brain damage in a sex-specific fashion, but the mechanisms involved are poorly described and remain controversial. Previous results have suggested that astrocyte gene expression is influenced by ethanol intoxication and during abstinence in vivo. Here, bioinformatic analysis of astrocyte-enriched ethanol-regulated genes in vivo revealed ubiquitin pathways as an ethanol target, but with sexually dimorphic cytokine signaling and changes associated with brain aging in females and not males. Consistent with this result, astrocyte activation was observed after exposure in female but not male animals, with reduced S100β levels in the anterior cingulate cortex and increased GFAP+ cells in the hippocampus. In primary culture, the direct effects of chronic ethanol exposure followed by recovery on sex-specific astrocyte function were examined. Male astrocyte responses were consistent with astrocyte deactivation with reduced GFAP expression during ethanol exposure. In contrast, female astrocytes exhibited increased expression of Tnf, reduced expression of the neuroprotective cytokine Tgfb1, disrupted bioenergetics and reduced excitatory amino acid uptake following exposure or recovery. These results indicate widespread astrocyte dysfunction in ethanol-exposed females and suggest a mechanism that may underlie increased vulnerability to ethanol-induced neurotoxicity in females.

Original languageEnglish (US)
Pages (from-to)433-451
Number of pages19
JournalBrain Pathology
Volume26
Issue number4
DOIs
StatePublished - Jul 1 2016

Keywords

  • alcohol
  • astrocyte
  • glutamate uptake
  • sexually dimorphic
  • tumor necrosis factor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

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    Wilhelm, C., Hashimoto, J. G., Roberts, M. L., Bloom, S. H., Andrew, M. R., & Wiren, K. (2016). Astrocyte Dysfunction Induced by Alcohol in Females but Not Males. Brain Pathology, 26(4), 433-451. https://doi.org/10.1111/bpa.12276