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Updated: Aug 11, 2026
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
A novel role for Sema3A in neuroprotection from injury mediated by activated microglia
Henry H Majed1, Siddharthan Chandran, Simone P Niclou
1Department of Clinical Neurosciences, Centre for Brain Repair, University of Cambridge, Forvie Site, Cambridge CB2 2PY, United Kingdom.
Abstract:
Microglia exist under physiological conditions in a resting state but become activated after neuronal injury. Recent studies have highlighted the reciprocal role of neurons in controlling both the number and activity of microglia. In this study, microglia derived from newborn rat cortices were cultured and activated by interferon-gamma (IFNgamma) treatment, then exposed to recombinant Sema3A or conditioned medium derived from stressed embryonic cortical neurons. We found that activation of microglia by IFNgamma induced differential upregulation of the semaphorin receptors Plexin-A1 and Neuropilin-1. This result was confirmed by Northern blotting, reverse transcription-PCR, and Western blotting. Furthermore, recombinant Sema3A induced apoptosis of microglia when added to the in vitro culture, and a similar result was obtained on activated microglia when Sema3A was produced by stressed neurons. Using an in vivo model of microglia activation by striatal injection of lipopolysaccharide demonstrated a corresponding upregulation of Plexin-A1 and Neuropilin-1 in activated microglia and enhanced production of Sema3A by stressed adult neurons. These results suggest a novel semaphorin-mediated mechanism of neuroprotection whereby stressed neurons can protect themselves from further damage by activated microglia.
Insights
Stressed neurons signal activated microglia via semaphorin to induce apoptosis, offering a novel neuroprotection mechanism. This study reveals how neurons control microglia for self-protection after injury.
Area of Science:
- Neuroscience
- Immunology
Background:
- Microglia are immune cells in the brain, typically resting but activated by neuronal injury.
- Neurons play a crucial role in regulating microglia number and activity.
Purpose of the Study:
- To investigate the semaphorin-mediated communication between stressed neurons and activated microglia.
- To explore the role of semaphorin signaling in neuroprotection.
Main Methods:
- In vitro culture of rat microglia activated by interferon-gamma (IFNgamma).
- Exposure of activated microglia to recombinant semaphorin 3A (Sema3A) or conditioned medium from stressed neurons.
- Confirmation of receptor expression using Northern blotting, RT-PCR, and Western blotting.
- In vivo study involving lipopolysaccharide-induced microglia activation in rat striatum.
Main Results:
- IFNgamma-activated microglia showed increased expression of semaphorin receptors Plexin-A1 and Neuropilin-1.
- Recombinant Sema3A induced apoptosis in cultured activated microglia.
- Sema3A produced by stressed neurons also induced apoptosis in activated microglia.
- In vivo, activated microglia upregulated Plexin-A1 and Neuropilin-1, and stressed neurons increased Sema3A production.
Conclusions:
- A novel semaphorin-mediated neuroprotective mechanism exists where stressed neurons induce apoptosis in activated microglia.
- This signaling pathway allows neurons to protect themselves from further damage by modulating microglial activity.
