Astrocyte Activation via Stat3 Signaling Determines the Balance of Oligodendrocyte versus Schwann Cell Remyelination

Am J Pathol. 2015 Sep;185(9):2431-40. doi: 10.1016/j.ajpath.2015.05.011. Epub 2015 Jul 17.

Abstract

Remyelination within the central nervous system (CNS) most often is the result of oligodendrocyte progenitor cells differentiating into myelin-forming oligodendrocytes. In some cases, however, Schwann cells, the peripheral nervous system myelinating glia, are found remyelinating demyelinated regions of the CNS. The reason for this peripheral type of remyelination in the CNS and what governs it is unknown. Here, we used a conditional astrocytic phosphorylated signal transducer and activator of transcription 3 knockout mouse model to investigate the effect of abrogating astrocyte activation on remyelination after lysolecithin-induced demyelination of spinal cord white matter. We show that oligodendrocyte-mediated remyelination decreases and Schwann cell remyelination increases in lesioned knockout mice in comparison with lesioned controls. Our study shows that astrocyte activation plays a crucial role in the balance between Schwann cell and oligodendrocyte remyelination in the CNS, and provides further insight into remyelination of CNS axons by Schwann cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Cells, Cultured
  • Central Nervous System / metabolism
  • Demyelinating Diseases / metabolism*
  • Mice, Knockout
  • Myelin Sheath / pathology*
  • Myelin Sheath / physiology
  • Nerve Regeneration / physiology
  • Neuroglia / metabolism
  • Oligodendroglia / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Schwann Cells / metabolism*
  • Stem Cells / metabolism

Substances

  • STAT3 Transcription Factor
  • Stat3 protein, mouse