title: Astrocytes in aged nonhuman primate brain gray matter synthesize excess hyaluronan.
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.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Cargill
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kohama
authors.forename: Jaime
authors.initials: J
authors.lastname: Struve
authors.forename: Weiping
authors.initials: W
authors.lastname: Su
authors.forename: Fatima
authors.initials: F
authors.lastname: Banine
authors.forename: Ellen
authors.initials: E
authors.lastname: Witkowski
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Back
authors.forename: Larry S
authors.initials: LS
authors.lastname: Sherman
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases