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Related Experiment Video

Updated: Mar 29, 2026

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Extracellular Succinate Modulates Neuroimmune Responses in a Murine Microglial Cell Line.

Samantha C Y Yudin1, Kimberly Day2, Erica Y Scott1

  • 1Department of Biology, Faculty of Science, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada.

Biomolecules
|March 28, 2026
PubMed
Summary

Extracellular succinate acts as a novel damage-associated molecular pattern (DAMP) that reduces neuroinflammation. This study shows extracellular succinate has anti-inflammatory effects on microglia, unlike intracellular succinate.

Keywords:
damage-associated molecular patternsgliaimmunometabolismintercellular signalingmitochondrial respirationneurodegenerative diseasesneuroinflammation

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Area of Science:

  • Neuroscience
  • Immunology
  • Metabolism

Background:

  • Neuroinflammation, driven by reactive microglia, is central to neuropathologies.
  • Damage-associated molecular patterns (DAMPs) trigger neuroinflammation.
  • Succinate's role as an extracellular DAMP in the central nervous system (CNS) is largely unknown.

Purpose of the Study:

  • To investigate the specific roles of extracellular and intracellular succinate in CNS neuroimmune responses.
  • To determine if succinate acts as a DAMP modulating microglial activity.

Main Methods:

  • Utilized cell membrane-impermeable disodium succinate for extracellular modeling and cell-permeable diethyl succinate for intracellular modeling in cell culture.
  • Assessed pro-inflammatory cytokine secretion (TNF-α, IL-6), microglial neurotoxicity, phagocytosis, and mitochondrial respiration.

Main Results:

  • Extracellular disodium succinate reduced pro-inflammatory cytokine secretion and microglial neurotoxic/phagocytic activities.
  • Extracellular succinate rescued lipopolysaccharide (LPS)-induced mitochondrial respiration deficits in human peripheral blood mononuclear cells (PBMCs).
  • Intracellular diethyl succinate reduced cytokine secretion but did not affect microglial neurotoxicity, indicating location-dependent effects.

Conclusions:

  • Extracellular succinate functions as a novel CNS DAMP.
  • Succinate exhibits predominantly anti-inflammatory actions on microglia when acting extracellularly.