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

• Published in: Journal of neuroscience research 2003-05, Vol.72 (4), p.425-435
• Main Authors: Roth, Alejandro D., Leisewitz, Andrea V., Jung, Juan E., Cassina, Patricia, Barbeito, Luis, Inestrosa, Nibaldo C., Bronfman, Miguel
• Format: Article
• Language: English
• Subjects: Alkyl and Aryl Transferases - drug effects; Alkyl and Aryl Transferases - metabolism; Anilides - pharmacology; Animals; B12 neural cells; Blotting, Western; Brain Neoplasms - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Division - drug effects; Cells, Cultured; differentiation; Immunohistochemistry; Lipid Metabolism; oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - physiology; PPAR; Protein Isoforms; Rats; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Spinal Cord - metabolism; Transcription Factors - agonists; Transcription Factors - antagonists & inhibitors; Transcription Factors - metabolism
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10596

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 PPARγ in the maturation process of these cells. B12 cells express all PPAR isoforms (α, β/δ, and γ), as assessed by RT‐PCR, Western‐blot, and transactivation assays. B12 cells respond specifically to PPARγ agonists by arresting cell proliferation and extending cell processes, events that are blocked by the PPARγ 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 PPARγ 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 PPARγ agonists with a four‐fold increase in the number of mature cells. Our data suggest a relevant role for PPARγ in oligodendrocyte lipid metabolism and differentiation. © 2003 Wiley‐Liss, Inc.