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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Oligodendroglial-derived stress signals recruit microglia in vitro
Richard Nicholas1, Sarah Stevens, Mark Wing
1University of Cambridge, Neurology Unit, Addenbrookes' Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Abstract:
Rat oligodendrocytes cultured without the essential survival factors serum and insulin die over a 48 h period. Analysis of supernatants from these dying cultures reveals a microglial chemokine released in advance of significant cell death. The observed microglial chemotactic effect is dose-dependent and not due to release of cellular debris. Interferon (IFN)-gamma activated microglia are more sensitive to the microglial chemokine. We show in co-culture that recruited non-activated microglia can enhance oligodendroglial survival whereas IFN-gamma activation of microglia induces contact-dependent oligodendroglial death. Thus, whilst the initial recruitment of microglia by stressed oligodendroglia may represent part of a survival process engaged by injured cells, this does not necessarily ensure survival.
Insights
Oligodendrocytes, essential for nerve insulation, die without survival factors. Microglia are recruited by dying cells, but their activation by interferon-gamma paradoxically causes oligodendrocyte death.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Oligodendrocytes are crucial for myelin sheath formation in the central nervous system.
- Oligodendrocyte survival is dependent on specific factors like serum and insulin.
- Microglia play complex roles in central nervous system homeostasis and disease.
Purpose of the Study:
- To investigate the interaction between dying oligodendrocytes and microglia.
- To determine the role of microglial chemokines in oligodendrocyte survival.
- To elucidate the impact of microglial activation state on oligodendrocyte fate.
Main Methods:
- Primary rat oligodendrocyte cultures were established.
- Supernatants from dying oligodendrocyte cultures were analyzed for chemokine presence.
- Co-culture systems were used to study oligodendrocyte-microglial interactions.
- Interferon-gamma (IFN-gamma) was employed to activate microglia.
Main Results:
- Dying oligodendrocytes release a dose-dependent microglial chemokine.
- Recruited, non-activated microglia promoted oligodendrocyte survival.
- IFN-gamma-activated microglia induced contact-dependent oligodendrocyte death.
- Microglial recruitment by stressed oligodendrocytes does not guarantee survival.
Conclusions:
- Oligodendrocyte stress triggers microglial recruitment via chemokines.
- The functional outcome of microglial interaction depends on their activation state.
- IFN-gamma activation of microglia shifts their role from protective to detrimental for oligodendrocytes.
