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Agonists specific for the transcription factor PPARdelta accelerate differentiation of oligodendrocytes
Author(s) -
Skoff R. P.,
Bessert D.,
Saluja I.,
Granneman J.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.82.x
Subject(s) - agonist , receptor , transcription factor , biology , peroxisome proliferator activated receptor , nuclear receptor , medicine , endocrinology , microbiology and biotechnology , biochemistry , gene
Peroxisome proliferator activated receptors (PPARs) are transcription factors belonging to the nuclear hormone receptor superfamily that regulate key genes involved in lipid metabolism. PPARδ is ubiquitously expressed at low levels in many tissues and its function has remained elusive. However, we have shown that PPARδ is abundantly expressed in oligodendrocytes (Ols), suggesting this receptor plays a critical role in oligodendrocyte differentiation (Granneman et al. 1998 J. Neurosci. Res 51 , 563). We first investigated the effects of PPAR agonists on proliferation and differentiation of Ols in tissue culture. Primary glial and enriched Ol cultures were treated with ligands that specifically activate PPARγ and PPARδ (Berger et al. 1999 J. Biol. Chem . 274 , 6717). PPARδ but not PPARγ agonists increased the size of OL membrane sheets within 24 h of application. The increase in membrane sheet size was mirrored by increases in MBP and PLP mRNA's. In enriched Ol cultures, the number of Ols was increased 70% with the PPARδ agonist but not the PPARγ agonist (Saluja et al. 2001 Glia 33 , 191). In vivo injections of PPARδ agonist into P2 and P3 mice show an increase of total macroglia in the ventral and dorsal funiculi of the spinal cord of 20–40% compared to controls. Preliminary observations suggest the Ols in agonist treated cultures are larger and more densely stained than controls. Our results show for the first time that a specific ligand for a transcription factor is capable of activating the program of Ol differentiation. Acknowledgements: Supported by NMSS.