Regulation of Oligodendrocyte Progenitor Cell Maturation by PPAR: Effects on Bone Morphogenetic Proteins
In EAE (experimental autoimmune encephalomyelitis), agonists of PPARs (peroxisome proliferator-activated receptors) provide clinical benefit and reduce damage. In contrast with PPAR γ , agonists of PPAR δ are more effective when given at later stages of EAE and increase myelin gene expression, sugge...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2009-12-01
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| Series: | ASN Neuro |
| Online Access: | https://doi.org/10.1042/AN20090033 |
| Summary: | In EAE (experimental autoimmune encephalomyelitis), agonists of PPARs (peroxisome proliferator-activated receptors) provide clinical benefit and reduce damage. In contrast with PPAR γ , agonists of PPAR δ are more effective when given at later stages of EAE and increase myelin gene expression, suggesting effects on OL (oligodendrocyte) maturation. In the present study we examined effects of the PPAR δ agonist GW0742 on OPCs (OL progenitor cells), and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins). We show that effects of GW0742 are mediated through PPAR δ since no amelioration of EAE clinical scores was observed in PPAR δ -null mice. In OPCs derived from E13 mice (where E is embryonic day), GW0742, but not the PPAR γ agonist pioglitazone, increased the number of myelin-producing OLs. This was due to activation of PPAR δ since process formation was reduced in PPAR δ -null compared with wild-type OPCs. In both OPCs and enriched astrocyte cultures, GW0742 increased noggin protein expression; however, noggin mRNA was only increased in astrocytes. In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPAR δ plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists. |
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| ISSN: | 1759-0914 1759-9091 |