Cord blood administration induces oligodendrocyte survival through alterations in gene expression

D. D. Rowe, C. C. Leonardo, A. A. Hall, M. D. Shahaduzzaman, L. A. Collier, A. E. Willing, K. R. Pennypacker

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Oligodendrocytes (OLs), the predominant cell type found in cerebral white matter, are essential for structural integrity and proper neural signaling. Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) cells protects striatal white matter tracts in vivo and directly protects mature primary OL cultures from oxygen glucose deprivation (OGD). Microarray studies of RNA prepared from OL cultures subjected to OGD and treated with HUCB cells showed an increase in the expression of 33 genes associated with OL proliferation, survival, and repair functions, such as myelination. The microarray results were verified using quantitative RT-PCR for the following eight genes: U2AF homology motif kinase 1 (Uhmk1), insulin-induced gene 1 (Insig1), metallothionein 3 (Mt3), tetraspanin 2 (Tspan2), peroxiredoxin 4 (Prdx4), stathmin-like 2 (Stmn2), myelin oligodendrocyte glycoprotein (MOG), and versican (Vcan). Immunohistochemistry showed that MOG, Prdx4, Uhmk1, Insig1, and Mt3 protein expression were upregulated in the ipsilateral white matter tracts of rats infused with HUCB cells 48 h after middle cerebral artery occlusion (MCAO). Furthermore, promoter region analysis of these genes revealed common transcription factor binding sites, providing insight into the shared signal transduction pathways activated by HUCB cells to enhance transcription of these genes. These results show expression of genes induced by HUCB cell therapy that could confer oligoprotection from ischemia.

Original languageEnglish
Pages (from-to)172-188
Number of pages17
JournalBrain Research
Volume1366
DOIs
StatePublished - 2010

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health ( R01 NS052839 ), the American Heart Association ( 0715096B to A.A.H.), and the University of South Florida Department of Molecular Pharmacology and Physiology. The authors also thank Dr. Javier Cuevas and the H. Lee. Moffitt Cancer Center Microarray core for their contributions.

Keywords

  • Anti-oxidant
  • Human umbilical cord blood cells
  • Ischemia
  • Microarray
  • Stroke
  • White matter

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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