Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12152-12164 |
| Number of pages | 13 |
| Journal | Journal of Neuroscience |
| Volume | 32 |
| Issue number | 35 |
| DOIs | |
| State | Published - Aug 29 2012 |
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ASJC Scopus subject areas
- Neuroscience(all)
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PEDF is a novel oligodendrogenic Morphogen acting on the adult SVZ and corpus callosum. / Sohn, Jiho; Selvaraj, Vimal; Wakayama, Kouji; Orosco, Lori; Lee, Eunyoung; Crawford, Susan E.; Guo, Fuzheng; Lang, Jordan; Horiuchi, Makoto; Zarbalis, Konstantinos; Ito, Takayuki; Deng, Wenbin; Pleasure, David E.
In: Journal of Neuroscience, Vol. 32, No. 35, 29.08.2012, p. 12152-12164.Research output: Contribution to journal › Article
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TY - JOUR
T1 - PEDF is a novel oligodendrogenic Morphogen acting on the adult SVZ and corpus callosum
AU - Sohn, Jiho
AU - Selvaraj, Vimal
AU - Wakayama, Kouji
AU - Orosco, Lori
AU - Lee, Eunyoung
AU - Crawford, Susan E.
AU - Guo, Fuzheng
AU - Lang, Jordan
AU - Horiuchi, Makoto
AU - Zarbalis, Konstantinos
AU - Ito, Takayuki
AU - Deng, Wenbin
AU - Pleasure, David E
PY - 2012/8/29
Y1 - 2012/8/29
N2 - 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.
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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84865500023&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0628-12.2012
DO - 10.1523/JNEUROSCI.0628-12.2012
M3 - Article
VL - 32
SP - 12152
EP - 12164
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 35
ER -