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Updated: Apr 17, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Up-regulation of glutamine synthesis in microglia activated with endotoxin
Kazuyuki Nakajima1, Tomoyuki Kanamatsu2, Yosuke Takezawa1
1Department of Bioinformatics, Faculty of Engineering, Soka University, Tokyo 192-8577, Japan.
Abstract:
We previously verified that newborn rat brain-derived microglia have the ability to uptake (14)C-glutamate (Glu) through glutamate transporter-1. A given amount of Glu incorporated into microglia was suspected to be metabolized to glutamine (Gln). However, the ability of microglia to do this had not been demonstrated. Thus, in the present study we examined the possibility that primary rat microglia metabolize Glu into Gln. Immunocytochemical and immunoblotting studies indicated that the microglia express glutamine synthetase (GS) protein. As expected from these results, GS activity was actually detected in microglia, although the specific activity was lower than that of astrocytes. Considering this microglial property, it seemed possible that the taken Glu is metabolized to Gln in the cells. To investigate this possibility, we exposed microglia to [(13)C]Glu-containing medium and analyzed the change of Glu to Gln in a nuclear magnetic resonance examination. The results clarified that non-stimulated microglia hardly changed Glu to Gln, but when stimulated with lipopolysaccharide the microglia significantly metabolized [(13)C]Glu to [(13)C]Gln. Microglia were thus, strongly suggested to metabolize Glu to Gln via GS activity when activated in the inflammatory/pathological state of the nervous system.
Insights
Activated microglia can convert glutamate to glutamine, a process mediated by glutamine synthetase. This finding is crucial for understanding neuroinflammation and brain metabolism.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Microglia, the immune cells of the central nervous system, are known to uptake glutamate (Glu) via glutamate transporter-1.
- It was hypothesized that microglia might metabolize intracellular Glu into glutamine (Gln), but this function remained unproven.
Purpose of the Study:
- To investigate the capacity of primary rat microglia to metabolize glutamate into glutamine.
- To determine the role of glutamine synthetase (GS) in this metabolic process within microglia.
Main Methods:
- Immunocytochemistry and immunoblotting were used to detect GS protein expression in microglia.
- GS enzymatic activity assays were performed on microglial cell extracts.
- Nuclear magnetic resonance (NMR) spectroscopy was employed to track the conversion of [(13)C]Glu to [(13)C]Gln in microglia under different stimulation conditions.
Main Results:
- Microglia were confirmed to express glutamine synthetase (GS) protein and exhibit GS activity, albeit at lower levels than astrocytes.
- Non-stimulated microglia showed minimal conversion of glutamate to glutamine.
- Lipopolysaccharide (LPS) stimulation significantly enhanced the metabolism of [(13)C]Glu to [(13)C]Gln in microglia.
Conclusions:
- Primary rat microglia possess the enzymatic machinery (GS) to convert glutamate to glutamine.
- Microglial glutamate-to-glutamine metabolism is significantly upregulated upon activation, particularly in inflammatory or pathological conditions.
- This metabolic capability suggests a role for microglia in modulating glutamate levels and supporting neuronal function during neuroinflammation.
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