REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
This article is part of the Research TopicNeuro-glial communication through the dynamic interstitial spaceView all articles
Microglia-Derived Metabolites as Novel Signaling Molecules: Regulating Neural Circuit Function, Behavior, and Their Role in Psychiatric Disorders
Provisionally accepted
- Heilongjiang University of Chinese Medicine, Harbin, China
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Microglia, central immune and metabolic regulators, release metabolites that act as signaling molecules into the interstitial space within the neuro‑immune‑metabolic axis (NIMA)(1). This review synthesizes evidence on how microglia‑derived metabolites modulate neural circuit function—affecting synaptic plasticity, network oscillations, and behavior—and how their dysregulation contributes to psychiatric disorders. We highlight the dynamic role of the interstitial space in shaping metabolite signaling and discuss therapeutic strategies targeting this axis. Reconceptualizing microglial metabolites as active circuit modulators offers novel insights into psychiatric pathophysiology and potential metabolic interventions.
Keywords: Interstitial space, Itaconate, Kynurenine, Lactate, Metabolites, Microglia, neuro‑immune‑metabolic axis, succinate
Received: 04 Oct 2025; Accepted: 06 Feb 2026.
Copyright: © 2026 李 and 赵. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: 永厚 赵
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