Related Experiment Videos
Basic fibroblast growth factor down-regulates myelin basic protein gene expression and alters myelin compaction of
C Fressinaud1, J M Vallat, G Labourdette
1Service de Neurologie, Hôpital Universitaire, Limoges, France.
Abstract:
The effects of basic fibroblast growth factor (bFGF) on myelin basic protein (MBP) gene expression and myelin-like membrane formation were investigated in oligodendrocyte cultures containing mainly mature oligodendrocytes expressing MBP. These cultures were obtained by selective detachment of the cells of the oligodendrocyte lineage from 40-day-old mixed cultures derived from newborn rat brain. They were further purified by a 3-day pretreatment with cytosine arabinoside (ARA-C) in order to kill cycling cells. After withdrawal of ARA-C, daily treatment of the cells with bFGF for 3 days induced a drastic decrease in MBP mRNA level compared to control cultures treated only with ARA-C. Moreover, the percentage of oligodendrocytes labelled with anti-MBP antibodies decreased by 50%, as well as that of oligodendrocytes expressing myelin oligodendrocyte glycoprotein (MOG), whereas proteolipid protein (PLP) immunolabelled cells were less affected. At the ultrastructural level, myelin-like membranes were still abundant in the ARA-C- and bFGF-treated cultures, but they were conspicuously uncompacted compared to cultures only pretreated with ARA-C. These results bring the first evidence that bFGF is able to down-regulate myelin protein gene expression in mature oligodendrocytes and to alter myelin structure. They imply that if bFGF is secreted after a demyelinating lesion of the central nervous system (CNS), this plasticity of mature oligodendrocytes will allow final remyelination of axons to complete only after this factor has returned to low levels.
Insights
Basic fibroblast growth factor (bFGF) reduces myelin basic protein (MBP) gene expression in mature oligodendrocytes. This factor also impairs myelin structure, potentially delaying remyelination after CNS injury.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Oligodendrocytes are crucial for myelin sheath formation in the central nervous system (CNS).
- Myelin basic protein (MBP) is a key component of the myelin sheath.
- Basic fibroblast growth factor (bFGF) is involved in cell growth and differentiation.
Purpose of the Study:
- To investigate the effects of bFGF on MBP gene expression in mature oligodendrocytes.
- To examine bFGF's impact on myelin-like membrane formation.
- To understand bFGF's role in oligodendrocyte plasticity and CNS remyelination.
Main Methods:
- Primary oligodendrocyte cultures were established from newborn rat brains.
- Cultures were purified using cytosine arabinoside (ARA-C) to isolate mature oligodendrocytes.
- Cells were treated with bFGF, and MBP mRNA levels, protein expression (MBP, MOG, PLP), and myelin ultrastructure were analyzed.
Main Results:
- bFGF treatment significantly decreased MBP mRNA levels and MBP-expressing oligodendrocytes.
- bFGF also reduced the percentage of myelin oligodendrocyte glycoprotein (MOG)-expressing cells, with less effect on proteolipid protein (PLP).
- Myelin-like membranes in bFGF-treated cultures were abundant but uncompacted compared to controls.
Conclusions:
- bFGF down-regulates myelin protein gene expression in mature oligodendrocytes.
- bFGF alters myelin structure, leading to uncompacted membranes.
- Elevated bFGF levels after CNS demyelination may hinder complete remyelination by mature oligodendrocytes.