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Metabolic Reprogramming of Microglia in Neuroinflammation and Depression
Qingru Wu1, Jing Tian1, Yan Gu2
1Department of Neurology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
Abstract:
Depression is a highly heterogeneous psychiatric disorder with its pathogenesis increasingly linked to dysregulated neuroinflammation. Microglia, as the resident immune cells of the central nervous system (CNS), play a pivotal role in the initiation and progression of the neuroinflammation and the pathophysiology of depression. These cells exhibit a dual role in pro- and anti-inflammatory processes, dynamically regulating immune responses through immunometabolic reprogramming in response to environmental cues. This review elaborates how metabolic remodeling in microglia, particularly within glucose, lipid, and amino acid pathways, drives their polarization toward a pro-inflammatory phenotype. This shift promotes depression pathogenesis via the release of inflammatory factors, disruption of synaptic plasticity, and mediation of neurotoxicity. We further discuss the impact of existing antidepressants on cellular metabolism and highlight the promise and challenges of targeting specific microglial metabolic pathways as a novel therapeutic strategy. This synthesis provides new insights into the immunometabolic mechanisms of depression and outlines directions for developing targeted treatments.
Insights
Microglia
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Depression pathogenesis is linked to neuroinflammation.
- Microglia, the CNS immune cells, are key players in neuroinflammation and depression.
- Microglia have dual roles, regulated by immunometabolic reprogramming.
Purpose of the Study:
- To review how microglial metabolic remodeling drives neuroinflammation in depression.
- To explore targeting microglial metabolism for novel depression therapies.
Main Methods:
- Review of literature on microglial immunometabolism and depression.
- Analysis of metabolic pathways (glucose, lipid, amino acid) in microglia.
- Discussion of antidepressant effects on cellular metabolism.
Main Results:
- Microglial metabolic reprogramming, especially in glucose, lipid, and amino acid pathways, promotes a pro-inflammatory phenotype.
- This pro-inflammatory shift contributes to depression via inflammatory factors, synaptic disruption, and neurotoxicity.
- Existing antidepressants impact cellular metabolism.
Conclusions:
- Microglial immunometabolic reprogramming is a significant factor in depression.
- Targeting microglial metabolic pathways offers a promising therapeutic strategy for depression.
- Further research is needed to develop targeted treatments based on these findings.
