Member of the peroxisome proliferator-activated receptor family of transcription factors is differentially expressed by oligodendrocytes

Abstract

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, PPARγ, 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 PPARδ, whereas adipose tissue expresses mainly PPARγ. In situ hybridization of primary glial cultures revealed PPARδ message in oligodendrocytes but not in astrocytes. PPARδ 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 PPARδ 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.