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Various Energetic Metabolism of Microglia in Response to Different Stimulations

Xiaohui Liu1,2,3, Ning Jiang2,3, Wenxia Zhou1,2,3

  • 1School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Molecules (Basel, Switzerland)
|June 10, 2023
PubMed

Insights

Microglia activation in Alzheimer's disease (AD) involves diverse metabolic changes. Targeting microglial metabolism, particularly glycolysis, shows potential for interfering with AD-related pathological changes.

Area of Science:

  • Neuroscience
  • Immunology
  • Metabolism

Background:

  • Microglia activation is central to neuroinflammation in Alzheimer's disease (AD).
  • Stimuli like PAMPs, DAMPs, and cytokines trigger distinct microglial responses and metabolic shifts in AD.
  • The specific metabolic differences in microglia under various stimuli remain unclear.

Purpose of the Study:

  • To investigate microglial cell type responses and energetic metabolism changes induced by LPS (PAMP), Aβ and ATP (DAMPs), and IL-4 (cytokine).
  • To explore whether targeting microglial metabolism can modulate AD-related microglial responses.

Main Methods:

  • Utilized BV-2 cells, a mouse-derived immortalized microglia cell line.
  • Exposed cells to lipopolysaccharide (LPS), amyloid-beta (Aβ), adenosine triphosphate (ATP), and interleukin-4 (IL-4).
  • Assessed changes in cell morphology, viability, fusion rates, phagocytosis, glycolysis, and oxidative phosphorylation (OXPHOS).

Main Results:

  • LPS induced a shift towards glycolysis and inhibited OXPHOS, enhancing microglial functions.
  • Aβ and ATP caused amoeboid morphology and variable metabolic changes, impacting functions differently.
  • IL-4 exposure resulted in minimal pathological and metabolic alterations.
  • Inhibiting glycolysis reversed LPS-induced pro-inflammatory changes, while promoting glycolysis had minimal impact on ATP-induced changes.

Conclusions:

  • Microglia exhibit diverse pathological and metabolic responses to different stimuli (PAMPs, DAMPs, cytokines).
  • Targeting microglial cellular metabolism presents a potential therapeutic strategy for AD.
  • Understanding stimulus-specific metabolic pathways is crucial for developing effective interventions.
Keywords:
Alzheimer’s diseaseDAMPsPAMPscytokinesenergetic metabolismmicroglia

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