Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation

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Preparation of Rat Oligodendrocyte Progenitor Cultures and Quantification of Oligodendrogenesis Using Dual-infrared Fluorescence Scanning
11:11

Preparation of Rat Oligodendrocyte Progenitor Cultures and Quantification of Oligodendrogenesis Using Dual-infrared Fluorescence Scanning

Published on: February 17, 2016

Gareth R John1, Sai Latha Shankar, Bridget Shafit-Zagardo

  • 1Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, New York, USA. gljohn@aecom.yu.edu

Nature Medicine
|October 3, 2002
PubMed

Insights

The Notch pathway, re-expressed in multiple sclerosis (MS) lesions, limits remyelination. Transforming growth factor-beta 1 (TGF-beta 1) induces Jagged1, inhibiting oligodendrocyte maturation and repair in the central nervous system (CNS).

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • During central nervous system (CNS) development, Notch1 signaling inhibits oligodendrocyte maturation.
  • Multiple sclerosis (MS) is characterized by limited remyelination.
  • The role of Notch signaling in adult CNS remyelination is not well understood.

Purpose of the Study:

  • To investigate the re-expression of the Notch pathway in the adult CNS of MS patients.
  • To determine the role of Notch signaling in the limited remyelination observed in MS.

Main Methods:

  • Primary cultures of human astrocytes and oligodendrocytes were used.
  • Immunohistochemistry was performed on active and remyelinated MS lesions.
  • Transforming growth factor-beta 1 (TGF-beta 1) and Jagged1 expression were analyzed.
  • In vitro experiments assessed the effect of Jagged1 signaling on oligodendrocyte process outgrowth.

Main Results:

  • Transforming growth factor-beta 1 (TGF-beta 1), upregulated in MS, re-induced Jagged1 in astrocytes.
  • Active MS plaques showed high Jagged1 expression by astrocytes and Notch1/Hes5 in immature oligodendrocytes.
  • Jagged1 expression was negligible in remyelinated lesions.
  • In vitro, Jagged1 signaling inhibited oligodendrocyte process outgrowth.

Conclusions:

  • The Notch pathway is implicated in the limited remyelination in multiple sclerosis (MS).
  • Jagged1, induced by TGF-beta 1, may inhibit oligodendrocyte maturation and repair in MS.
  • Targeting the Notch pathway could be a potential therapeutic strategy for MS.

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