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11:11
Preparation of Rat Oligodendrocyte Progenitor Cultures and Quantification of Oligodendrogenesis Using Dual-infrared Fluorescence Scanning
Published on: February 17, 2016
Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation
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
Summary
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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