Member of the peroxisome proliferator-activated receptor family of transcription factors is differentially expressed by oligodendrocytes.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that form a subfamily within the steroid hormone receptor group. Recent work has shown that one member of this group, PPARgamma, plays a central role in adipocyte differentiation. As oligodendrocytes are major lipid-producing cells, we investigated whether members of the PPAR family were present in oligodendrocytes and whether known PPAR activators affect oligodendrocyte differentiation. Polymerase chain reaction and nuclease protection analyses demonstrated that the principal PPAR present in optic nerve and sciatic nerve is PPARdelta, whereas adipose tissue expresses mainly PPARgamma. In situ hybridization of primary glial cultures revealed PPARdelta message in oligodendrocytes but not in astrocytes. PPARdelta message was strongly expressed in immature oligodendrocytes, suggesting a role in oligodendrocyte differentiation. Glial cultures containing immature oligodendrocytes were treated with CP 68,722 and bromopalmitate, compounds known to activate PPARs in adipocytes. These agents increased the number of oligodendrocytes with membrane sheets three- to fourfold, accelerated the rate of formation of membrane sheets, and increased the size of the membrane sheets. The abundant expression of PPARdelta in oligodendrocytes in vivo and in vitro suggests that this PPAR plays a critical role in oligodendrocyte development and that PPAR activators can be used to manipulate oligodendrocyte maturation in tissue culture.
Granneman
J
J
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Skoff
R
R
Yang
X
X
D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology; D017403:In Situ Hybridization; D008830:Microbodies / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009900:Optic Nerve; D010168:Palmitates / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012584:Sciatic Nerve; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics*
D001578:Benzopyrans; D007004:Hypoglycemic Agents; D009687:Nuclear Proteins; D010168:Palmitates; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C022776:2-bromopalmitate; C066021:englitazone