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Microglia Sing the Prelude of Neuroinflammation-Associated Depression
Qingqing Li1, Ying Xie1, Jinyi Lin1
1Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
Abstract:
Major depressive disorder (MDD) is a psychiatric condition characterized by sadness and anhedonia and is closely linked to chronic low-grade neuroinflammation, which is primarily induced by microglia. Nonetheless, the mechanisms by which microglia elicit depressive symptoms remain uncertain. This review focuses on the mechanism linking microglia and depression encompassing the breakdown of the blood-brain barrier, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, the vagus and sympathetic nervous systems, and the susceptibility influenced by epigenetic modifications on microglia. These pathways may lead to the alterations of microglia in cytokine levels, as well as increased oxidative stress. Simultaneously, many antidepressant treatments can alter the immune phenotype of microglia, while anti-inflammatory treatments can also have antidepressant effects. This framework linking microglia, neuroinflammation, and depression could serve as a reference for targeting microglia to treat depression.
Insights
Major depressive disorder (MDD) is linked to neuroinflammation caused by microglia. This review explores how microglia contribute to depression via various pathways, suggesting microglia as a therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Major depressive disorder (MDD) is associated with chronic neuroinflammation, primarily driven by microglia.
- The precise mechanisms by which microglia induce depressive symptoms are not fully understood.
Purpose of the Study:
- To review the mechanisms linking microglia and depression.
- To explore the role of microglia in neuroinflammation and its connection to MDD.
Main Methods:
- Literature review focusing on pathways connecting microglia to depression.
- Analysis of the influence of blood-brain barrier integrity, neuroendocrine axes, nervous systems, and epigenetics on microglia.
Main Results:
- Microglia activation contributes to depression through pathways including blood-brain barrier dysfunction, HPA axis dysregulation, gut-brain axis alterations, and nervous system modulation.
- Epigenetic modifications influence microglial susceptibility and function.
- Altered microglial cytokine levels and increased oxidative stress are key consequences.
- Both antidepressant and anti-inflammatory treatments can modulate microglial immune phenotypes and exert antidepressant effects.
Conclusions:
- A framework linking microglia, neuroinflammation, and depression is established.
- Targeting microglia presents a potential therapeutic strategy for treating depression.
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