Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes

Jason F. Talbott, David N. Loy, Ying Liu, Mengsheng S. Qiu, Mary B Bunge, Mahendra S. Rao, Scott R. Whittemore

Research output: Contribution to journalArticle

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Abstract

Chronic demyelination is a pathophysiologic component of compressive spinal cord injury (SCI) and a characteristic finding in demyelinating diseases including multiple sclerosis (MS). A better characterization of endogenous cells responsible for successful remyelination is essential for designing therapeutic strategies aimed at restoring functional myelin. The present study examined the spatiotemporal response of endogenous oligodendrocyte precursor cells (OPCs) following ethidium bromide (EB)-induced demyelination of the adult rat spinal cord. Beginning at 2 days post-EB injection (dpi), a robust mobilization of highly proliferative NG2+ cells within the lesion was observed, none of which expressed the oligodendrocyte lineage-associated transcription factor Nkx2.2. At 7 dpi, a significant up-regulation of Nkx2.2 by OPCs within the lesion was observed, 90% of which coexpressed NG2 and virtually all of which coexpressed the bHLH transcription factor Olig2. Despite successful recruitment of Nkx2.2+/Olig2+ OPCs within the lesion, demyelinated axons were not remyelinated by these OPCs in regions lacking astrocytes. Rather, Schwann cell remyelination predominated throughout the central core of the lesion, particularly around blood vessels. Oligodendrocyte remyelination was observed in the astrogliotic perimeter, suggesting a necessary role for astrocytes in oligodendrocyte maturation. In addition, reexpression of the radial glial antigen, RC-1, by reactive astrocytes and ependymal cells was observed following injury. However, these cells did not express the neural stem cell (NSC)-associated transcription factors Sox1 or Sox2, suggesting that the endogenous response is primarily mediated by glial progenitors. In vivo electrophysiology demonstrated a limited and unsustained functional recovery concurrent with endogenous remyelination following EB-induced lesions.

Original languageEnglish
Pages (from-to)11-24
Number of pages14
JournalExperimental Neurology
Volume192
Issue number1
DOIs
StatePublished - Mar 1 2005

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Oligodendroglia
Astrocytes
Spinal Cord
Ethidium
Demyelinating Diseases
Neuroglia
Transcription Factors
Basic Helix-Loop-Helix Transcription Factors
Injections
Neural Stem Cells
Electrophysiology
Schwann Cells
Myelin Sheath
Spinal Cord Injuries
Multiple Sclerosis
Blood Vessels
Axons
Up-Regulation
Antigens
Wounds and Injuries

Keywords

  • Demyelination
  • NG2
  • Nkx2.2
  • Oligodendrocyte precursor cell
  • Radial glia
  • Remyelination

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes. / Talbott, Jason F.; Loy, David N.; Liu, Ying; Qiu, Mengsheng S.; Bunge, Mary B; Rao, Mahendra S.; Whittemore, Scott R.

In: Experimental Neurology, Vol. 192, No. 1, 01.03.2005, p. 11-24.

Research output: Contribution to journalArticle

Talbott, Jason F. ; Loy, David N. ; Liu, Ying ; Qiu, Mengsheng S. ; Bunge, Mary B ; Rao, Mahendra S. ; Whittemore, Scott R. / Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes. In: Experimental Neurology. 2005 ; Vol. 192, No. 1. pp. 11-24.
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