Abstract

Peroxisome proliferator-activated receptors (PPARs) are key transcription factors in the control of lipid homeostasis and cell differentiation, but little is known about their function in oligodendrocytes, the major lipid-synthesizing cells in the central nervous system (CNS). Using the B12 oligodendrocyte-like cell line and rat spinal cord-derived oligodendrocytes, we evaluated the importance of PPAR? in the maturation process of these cells. B12 cells express all PPAR isoforms (?, ?/?, and ?), as assessed by RT-PCR, Western-blot, and transactivation assays. B12 cells respond specifically to PPAR? agonists by arresting cell proliferation and extending cell processes, events that are blocked by the PPAR? antagonist GW9662. In addition, alkyl-dihydroxyacetone phosphate synthase (ADAPS), a key peroxisomal enzyme involved in the synthesis of myelin-rich lipid plasmalogens, is increased in PPAR? agonist-treated B12 cells. In contrast with B12 cells, both immature and mature isolated spinal cord oligodendrocytes presented a high and similar expression level of ADAPS, as assessed by immunocytochemistry. However, as in B12 cells, isolated spinal cord oligodendrocytes were also found to respond specifically to PPAR? agonists with a four-fold increase in the number of mature cells. Our data suggest a relevant role for PPAR? in oligodendrocyte lipid metabolism and differentiation © 2003 Wiley-Liss, Inc.