RT Journal Article
SR Electronic
T1 PEDF Is a Novel Oligodendrogenic Morphogen Acting on the Adult SVZ and Corpus Callosum
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12152
OP 12164
DO 10.1523/JNEUROSCI.0628-12.2012
VO 32
IS 35
A1 Jiho Sohn
A1 Vimal Selvaraj
A1 Kouji Wakayama
A1 Lori Orosco
A1 Eunyoung Lee
A1 Susan E. Crawford
A1 Fuzheng Guo
A1 Jordan Lang
A1 Makoto Horiuchi
A1 Konstantinos Zarbalis
A1 Takayuki Itoh
A1 Wenbin Deng
A1 David Pleasure
YR 2012
UL http://www.jneurosci.org/content/32/35/12152.abstract
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.