PEDF is a novel oligodendrogenic Morphogen acting on the adult SVZ and corpus callosum

Jiho Sohn, Vimal Selvaraj, Kouji Wakayama, Lori Orosco, Eunyoung Lee, Susan E. Crawford, Fuzheng Guo, Jordan Lang, Makoto Horiuchi, Konstantinos Zarbalis, Takayuki Ito, Wenbin Deng, David E Pleasure

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18 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)12152-12164
Number of pages13
JournalJournal of Neuroscience
Volume32
Issue number35
DOIs
StatePublished - Aug 29 2012

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Corpus Callosum
Lateral Ventricles
Glial Fibrillary Acidic Protein
Green Fluorescent Proteins
Lysophosphatidylcholines
Demyelinating Diseases
Transcription Factors
pigment epithelium-derived factor
Serine Proteinase Inhibitors
Transgenic Mice
Regeneration
Up-Regulation
Stem Cells
Western Blotting
Pharmacology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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 journalArticle

Sohn, J, Selvaraj, V, Wakayama, K, Orosco, L, Lee, E, Crawford, SE, Guo, F, Lang, J, Horiuchi, M, Zarbalis, K, Ito, T, Deng, W & Pleasure, DE 2012, 'PEDF is a novel oligodendrogenic Morphogen acting on the adult SVZ and corpus callosum', Journal of Neuroscience, vol. 32, no. 35, pp. 12152-12164. https://doi.org/10.1523/JNEUROSCI.0628-12.2012
Sohn J, Selvaraj V, Wakayama K, Orosco L, Lee E, Crawford SE et al. PEDF is a novel oligodendrogenic Morphogen acting on the adult SVZ and corpus callosum. Journal of Neuroscience. 2012 Aug 29;32(35):12152-12164. https://doi.org/10.1523/JNEUROSCI.0628-12.2012
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. / PEDF is a novel oligodendrogenic Morphogen acting on the adult SVZ and corpus callosum. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 35. pp. 12152-12164.
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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

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