PPAR gamma activators induce growth arrest and process extension in B12 oligodendrocyte-like cells and terminal differentiation of cultured oligodendrocytes

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 PPARgamma in the maturation process of these cells. B12 cells express all PPAR isoforms (alpha, beta/delta, and gamma), as assessed by RT-PCR, Western-blot, and transactivation assays. B12 cells respond specifically to PPARgamma agonists by arresting cell proliferation and extending cell processes, events that are blocked by the PPARgamma 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 PPARgamma 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 PPARgamma agonists with a four-fold increase in the number of mature cells. Our data suggest a relevant role for PPARgamma in oligodendrocyte lipid metabolism and differentiation.