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Review
. 2025 Apr;62(4):5311-5332.
doi: 10.1007/s12035-024-04575-w. Epub 2024 Nov 13.

Microglia Sing the Prelude of Neuroinflammation-Associated Depression

Qingqing Li  1 , Ying Xie  1 , Jinyi Lin  1 , Miaomiao Li  1 , Ziyan Gu  1 , Tianli Xin  1 , Yang Zhang  1 , Qixia Lu  1 , Yihui Guo  1 , Yanhong Xing  2 , Wuyang Wang  3
Affiliations
Review

Microglia Sing the Prelude of Neuroinflammation-Associated Depression

Qingqing Li et al. Mol Neurobiol. 2025 Apr.

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.

Keywords: Immunity; Major depressive disorder; Microglia; Neuroinflammation.

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Conflict of interest statement

Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests. Disclaimer: The funding organizations of this paper had no role in the design, article retrieval, writing, or the decision to submit the article for publication.

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