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Updated: May 25, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial activation in neuroinflammation: implications for the etiology of neurodegeneration
Yoko S Kaneko1, Akira Nakashima, Keiji Mori
1Department of Physiology, Fujita Health University School of Medicine, Toyoake, Japan.
Background:
Activated microglia secrete inflammatory cytokines and may play roles in the progression of neurodegenerative diseases. However, the mechanism underlying microglial activation remains unclear.
Objective:
Our aim was to examine the regulation of activated microglia through their cell death and survival pathways.
Methods:
We used mouse primary-cultured microglia, which are destined to die within a few days under ordinary culture conditions. The microglia live for longer than 1 month, without any measurable increase in apoptotic or necrotic cell death, when kept activated by sublethal concentrations of lipopolysaccharide (LPS).
Results:
LPS-treated microglia showed changes in shape. LPS treatment had no effect on the level of the proapoptotic Bcl-2-associated X protein but increased the level of the antiapoptotic protein Bcl-xL at day 1. Furthermore, the level of microtubule-associated light chain 3-II, a marker protein for autophagy, was decreased 3 h after exposure to LPS.
Conclusion:
An increase in Bcl-xL seems to inhibit both apoptosis and autophagy. Our results suggest that long-lived microglia resulting from exposure to the optimal dose of LPS may play critical roles in the progression of neurodegeneration.
Insights
Activated microglia, key in neurodegeneration, survive longer when treated with lipopolysaccharide (LPS). This survival is linked to increased Bcl-xL, inhibiting cell death and autophagy, suggesting a role in disease progression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Activated microglia release inflammatory cytokines, potentially driving neurodegenerative diseases.
- The precise mechanisms governing microglial activation and survival are not fully understood.
Purpose of the Study:
- To investigate the regulation of activated microglia concerning their cell death and survival pathways.
- To elucidate the molecular mechanisms behind microglial longevity under specific stimuli.
Main Methods:
- Utilized primary mouse microglia cultures.
- Maintained microglia in culture with sublethal lipopolysaccharide (LPS) concentrations to promote activation and survival.
- Assessed cell death (apoptosis, necrosis), protein levels (Bcl-2-associated X protein, Bcl-xL), and autophagy markers (microtubule-associated light chain 3-II).
Main Results:
- Lipopolysaccharide (LPS) treatment induced morphological changes in microglia.
- LPS exposure did not alter the proapoptotic Bcl-2-associated X protein but increased the antiapoptotic Bcl-xL protein level.
- A decrease in microtubule-associated light chain 3-II, an autophagy marker, was observed 3 hours post-LPS exposure.
Conclusions:
- Elevated Bcl-xL appears to concurrently inhibit apoptosis and autophagy in activated microglia.
- Sustained microglial activation and survival, induced by optimal LPS doses, may significantly contribute to the advancement of neurodegenerative conditions.
