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Myelination and remyelination of aggregate rat brain cell cultures enriched with macrophages
A J Loughlin1, C A Copelman, A Hall
1Department of Neurochemistry, Institute of Neurology, London, United Kingdom.
Abstract:
We reported previously that accumulation of myelin basic protein (MBP) in foetal brain aggregate cultures is enhanced by supplementation with peritoneal macrophages. The present study demonstrates that the rate of MBP accumulation in macrophage-enriched cultures continues to increase over time unaccompanied by a matching increase in the oligodendrocyte marker cyclic nucleotide phosphodiesterase, while that of control cultures reaches a plateau. These observations are supported by electron microscopic evidence of cumulative numbers of myelinated axons in the aggregates over time and by enhanced expression of myelin protein genes in macrophage-enriched relative to control cultures. Aggregates demyelinate following short-term exposure to cytokines and antimyelin oligodendrocyte glycoprotein antibody, and MBP synthesis resumes following removal of demyelinating agents. Supplementation of cultures with macrophages influences the degree of myelin breakdown and remyelination, drawing attention to the role that macrophage-derived growth factors may play in myelinogenesis and myelin repair in inflammatory demyelinating disease.
Insights
Peritoneal macrophages enhance myelin basic protein (MBP) accumulation in fetal brain cultures. Macrophage-enriched cultures show sustained MBP production, suggesting a role in myelin repair for demyelinating diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Myelin basic protein (MBP) accumulation is crucial for myelin formation.
- Peritoneal macrophages were previously shown to enhance MBP accumulation in fetal brain aggregates.
Purpose of the Study:
- To investigate the long-term effects of macrophage enrichment on myelin accumulation.
- To explore the role of macrophages in myelin repair and myelinogenesis.
Main Methods:
- Utilized fetal brain aggregate cultures supplemented with peritoneal macrophages.
- Monitored MBP accumulation and oligodendrocyte marker cyclic nucleotide phosphodiesterase.
- Employed electron microscopy to assess myelinated axons.
- Analyzed myelin protein gene expression.
- Induced demyelination using cytokines and antibodies, followed by assessment of remyelination.
Main Results:
- Macrophage-enriched cultures exhibited continuous MBP accumulation, unlike control cultures that plateaued.
- Electron microscopy confirmed cumulative myelinated axons in macrophage-enriched cultures.
- Enhanced expression of myelin protein genes was observed in macrophage-enriched cultures.
- Macrophages influenced myelin breakdown and subsequent remyelination.
Conclusions:
- Peritoneal macrophages promote sustained myelin basic protein accumulation and myelin repair.
- Macrophage-derived factors may play a significant role in myelinogenesis and recovery from inflammatory demyelinating diseases.