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Macrophage colony stimulating factor prevents NMDA-induced neuronal death in hippocampal organotypic cultures
Valerie A M Vincent1, Christopher C Robinson, Dilek Simsek
1Neuroscience Research Laboratories, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Abstract:
Macrophage colony stimulating factor (M-CSF) and its receptor are up-regulated in the brain in Alzheimer's disease (AD), in transgenic mouse models for AD, and experimental models for traumatic and ischemic brain injury. M-CSF induces activation and proliferation of microglial cells and expression of proinflammatory cytokines. We examined the role of M-CSF in excitotoxic neuronal cell death in organotypic hippocampal cultures. NMDA treatment induced neuronal apoptosis and caspase-3 activation in organotypic hippocampal cultures, whereas treatment with M-CSF protected hippocampal neurons from NMDA-induced apoptosis. Caspase-3 activation was inhibited by M-CSF treatment to the same degree as with the caspase inhibitor Z-VAD-FMK. These results suggest that M-CSF has neuroprotective properties through inhibition of caspase-3 that could promote neuronal survival after excitotoxic insult. The role of M-CSF in neurological disease should be reevaluated as a microglial activator with potentially neuroprotective effects.
Insights
Macrophage colony stimulating factor (M-CSF) has neuroprotective effects in the brain. It inhibits caspase-3 activation, promoting neuronal survival after excitotoxic injury, suggesting a reevaluation of its role in neurological diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Macrophage colony stimulating factor (M-CSF) and its receptor are elevated in Alzheimer's disease (AD) and brain injury models.
- M-CSF promotes microglial activation and the release of inflammatory cytokines.
Purpose of the Study:
- To investigate the role of M-CSF in excitotoxic neuronal cell death.
- To determine if M-CSF exhibits neuroprotective properties.
Main Methods:
- Organotypic hippocampal cultures were used to model excitotoxicity.
- Neurons were treated with NMDA to induce apoptosis and caspase-3 activation.
- The effects of M-CSF treatment on neuronal survival and caspase-3 activation were assessed.
Main Results:
- NMDA treatment caused neuronal apoptosis and caspase-3 activation.
- M-CSF treatment protected hippocampal neurons from NMDA-induced apoptosis.
- M-CSF significantly inhibited caspase-3 activation, comparable to a known caspase inhibitor.
Conclusions:
- M-CSF demonstrates neuroprotective properties by inhibiting caspase-3 activation.
- These findings suggest M-CSF may promote neuronal survival following excitotoxic insults.
- The role of M-CSF in neurological disorders warrants reevaluation for its potential neuroprotective effects.