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Updated: Dec 25, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial metabolic flexibility supports immune surveillance of the brain parenchyma
Louis-Philippe Bernier1, Elisa M York2, Alireza Kamyabi2
1University of British Columbia, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Columbia, Canada. lp.bernier@ubc.ca.
Abstract:
Microglia are highly motile cells that continuously monitor the brain environment and respond to damage-associated cues. While glucose is the main energy substrate used by neurons in the brain, the nutrients metabolized by microglia to support surveillance of the parenchyma remain unexplored. Here, we use fluorescence lifetime imaging of intracellular NAD(P)H and time-lapse two-photon imaging of microglial dynamics in vivo and in situ, to show unique aspects of the microglial metabolic signature in the brain. Microglia are metabolically flexible and can rapidly adapt to consume glutamine as an alternative metabolic fuel in the absence of glucose. During insulin-induced hypoglycemia in vivo or in aglycemia in acute brain slices, glutaminolysis supports the maintenance of microglial process motility and damage-sensing functions. This metabolic shift sustains mitochondrial metabolism and requires mTOR-dependent signaling. This remarkable plasticity allows microglia to maintain their critical surveillance and phagocytic roles, even after brain neuroenergetic homeostasis is compromised.
Insights
Microglia, the brain's immune cells, can switch to using glutamine for energy when glucose is unavailable. This metabolic flexibility maintains their crucial surveillance and damage-sensing functions during brain energy deficits.
Area of Science:
- Neuroscience
- Cell Biology
- Metabolism
Background:
- Microglia are essential brain immune cells responsible for continuous environmental monitoring and responding to damage.
- The primary energy source for neurons is glucose, but microglial nutrient metabolism for surveillance remains poorly understood.
Purpose of the Study:
- To investigate the metabolic signature of microglia and their nutrient utilization for maintaining brain surveillance functions.
- To explore microglial metabolic plasticity in response to glucose deprivation.
Main Methods:
- Utilized fluorescence lifetime imaging of intracellular NAD(P)H.
- Employed time-lapse two-photon imaging for in vivo and in situ microglial dynamics.
- Induced insulin-induced hypoglycemia in vivo and aglycemia in acute brain slices.
Main Results:
- Demonstrated that microglia exhibit metabolic flexibility, utilizing glutamine as an alternative fuel in the absence of glucose.
- Showed that glutaminolysis supports microglial process motility and damage-sensing functions during hypoglycemia or aglycemia.
- Identified that this metabolic shift sustains mitochondrial activity and depends on mTOR signaling.
Conclusions:
- Microglia possess remarkable metabolic plasticity, enabling them to maintain critical surveillance and phagocytic roles even when brain energy homeostasis is compromised.
- Glutamine metabolism is vital for microglial function during neuroenergetic challenges.
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