Glucose pathways adaptation supports acquisition of activated microglia phenotype

Area of Science:

• Neuroscience
• Cell Biology
• Metabolic Biochemistry

Background:

• Microglia, the immune cells of the central nervous system, exhibit diverse phenotypes with neurotrophic and toxic effects.
• The energetic mechanisms underlying microglial activation and their diverse functional roles remain largely unexplored.
• Understanding microglial metabolism is crucial for deciphering their contribution to neurological health and disease.

Purpose of the Study:

• To investigate the metabolic adaptations of microglia upon activation.
• To elucidate the production of ATP, NADPH, H+, and reactive oxygen species during microglial activation.
• To understand the role of nitric oxide (NO) in microglial energy metabolism.

Main Methods:

• In vitro studies using BV-2 microglial cells.
• Activation of BV-2 cells with lipopolysaccharide (LPS) + interferon-gamma (IFN-γ).
• Measurement of nitric oxide (NO) as a marker of microglial activation.
• Analysis of metabolic pathways including glucose uptake, glycolysis, pentose pathway, and mitochondrial activity.

Main Results:

• Microglial activation induced significant metabolic reprogramming.
• Increased glucose uptake and enhanced anaerobic glycolysis were observed.
• The oxidative branch of the pentose pathway was strengthened, while mitochondrial activity was maintained.
• Rapid increase in microglial defense capacity, ribose-5-phosphate, and nucleic acid formation for gene transcription.

Conclusions:

• Microglial activation is characterized by a metabolic shift favoring glycolysis and the pentose pathway to support heightened cellular functions.
• This metabolic reprogramming is essential for rapid defense responses and gene transcription required for central nervous system signaling.
• Nitric oxide plays a role in this energy commitment, linking cytotoxic microglia to the astrocyte-neuron lactate shuttle energetics.