Metabolic flexibility ensures proper neuronal network function in moderate neuroinflammation.

Area of Science:

• Neuroscience
• Cellular Metabolism
• Neuroinflammation

Background:

• Microglia, the brain's immune cells, can adopt different functional states.
• These states involve metabolic reprogramming, affecting energy substrate availability in the brain.
• The impact of microglia on neuronal energy metabolism during neuroinflammation is not well understood.

Purpose of the Study:

• To investigate how microglia influence brain energy metabolism during neuroinflammation.
• To understand the mechanisms behind microglia-mediated metabolic disturbances.
• To assess the consequences for neuronal network function.

Main Methods:

• Molecular profiling
• Electrophysiology
• Oxygen microsensor recordings
• Mathematical modeling of neuronal energetics

Main Results:

• Proinflammatory microglia transiently increase the tissue lactate/glucose ratio via transcriptional reprogramming.
• This metabolic shift supports neuronal network activity, such as gamma oscillations, through increased mitochondrial ATP production.
• Kinetic modeling revealed that high energy demand and low glucose availability can challenge neuronal metabolic health during severe inflammation.

Conclusions:

• Microglia play a critical role in modulating brain energy metabolism during neuroinflammation.
• Metabolic flexibility in neurons is crucial for maintaining network function under altered substrate availability.
• These findings highlight the intricate relationship between immune cells, metabolism, and neuronal function in the brain.