PT  - JOURNAL ARTICLE
AU  - Jiho Sohn
AU  - Vimal Selvaraj
AU  - Kouji Wakayama
AU  - Lori Orosco
AU  - Eunyoung Lee
AU  - Susan E. Crawford
AU  - Fuzheng Guo
AU  - Jordan Lang
AU  - Makoto Horiuchi
AU  - Konstantinos Zarbalis
AU  - Takayuki Itoh
AU  - Wenbin Deng
AU  - David Pleasure
TI  - PEDF Is a Novel Oligodendrogenic Morphogen Acting on the Adult SVZ and Corpus Callosum
AID  - 10.1523/JNEUROSCI.0628-12.2012
DP  - 2012 Aug 29
TA  - The Journal of Neuroscience
PG  - 12152--12164
VI  - 32
IP  - 35
4099  - http://www.jneurosci.org/content/32/35/12152.short
4100  - http://www.jneurosci.org/content/32/35/12152.full
SO  - J. Neurosci.2012 Aug 29; 32
AB  - Pigment epithelium-derived factor (PEDF) is a serine protease inhibitor (serpin) protein with well established neuroprotective and anti-angiogenic properties. Recent studies have also shown that PEDF enhances renewal of adult subventricular zone (SVZ) neural precursors. In neurosphere cultures prepared from the SVZ of adult mice, we found that addition of recombinant PEDF to the medium enhanced expressions of oligodendroglial lineage markers (NG2 and PDGFrα) and transcription factors (Olig1, Olig2, and Sox10). Similarly, continuous PEDF administration into the lateral ventricles of adult glial fibrillary acidic protein:green fluorescent protein (GFAP:GFP) transgenic mice increased the proportions of GFAP:GFP+ and GFAP:GFP− SVZ neural precursors coexpressing oligodendroglial lineage markers and transcription factors. Notably, PEDF infusion also resulted in an induction of doublecortin- and Sox10 double-positive cells in the adult SVZ. Immunoreactive PEDF receptor was detectable in multiple cell types in both adult SVZ and corpus callosum. Furthermore, PEDF intracerebral infusion enhanced survival and maturation of newly born oligodendroglial progenitor cells in the normal corpus callosum, and accelerated oligodendroglial regeneration in lysolecithin-induced corpus callosum demyelinative lesions. Western blot analysis showed a robust upregulation of endogenous PEDF in the corpus callosum upon lysolecithin-induced demyelination. Our results document previously unrecognized oligodendrotrophic effects of recombinant PEDF on the adult SVZ and corpus callosum, demonstrate induction of endogenous CNS PEDF production following demyelination, and make PEDF a strong candidate for pharmacological intervention in demyelinative diseases.