Astrocytes in aged nonhuman primate brain gray matter synthesize excess hyaluronan

Robert Cargill, Steven G. Kohama, Jaime Struve, Weiping Su, Fatima Banine, Ellen Witkowski, Stephen A. Back, Larry S. Sherman

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

The glycosaminoglycan hyaluronan (HA) accumulates in central nervous system lesions where it limits astrogliosis but also inhibits oligodendrocyte progenitor cell (OPC) maturation. The role of hyaluronan in normative brain aging has not been previously investigated. Here, we tested the hypothesis that HA accumulates in the aging nonhuman primate brain. We found that HA levels significantly increase with age in the gray matter of rhesus macaques. HA accumulation was linked to age-related increases in the transcription of HA synthase-1 (HAS1) expressed by reactive astrocytes but not changes in the expression of other HAS genes or hyaluronidases. HA accumulation was accompanied by increased expression of CD44, a transmembrane HA receptor. Areas of gray matter with elevated HA in older animals demonstrated increased numbers of olig2+ OPCs, consistent with the notion that HA may influence OPC expansion or maturation. Collectively, these data indicate that HAS1 and CD44 are transcriptionally upregulated in astrocytes during normative aging and are linked to HA accumulation in gray matter.

Original languageEnglish (US)
Pages (from-to)830.e13-830.e24
JournalNeurobiology of Aging
Volume33
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Aging
  • Astrocytes
  • Hyaluronan
  • Nonhuman primate
  • Oligodendrocyte progenitor cells

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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