Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications
Major depressive disorder (MDD) is one of the most common mental health conditions, characterized by pervasive and persistent low mood, low self-esteem, and a loss of interest or pleasure in activities that are typically enjoyable. Despite decades of research into the etiology and pathophysiological...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2025.1538026/full |
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| author | Kunying Zhao Kunying Zhao Yuxiao Zhang Yuxiao Zhang Shuda Yang Shuda Yang Lirong Xiang Lirong Xiang Shangpeng Wu Shangpeng Wu Junfang Dong Junfang Dong Huan Li Huan Li Haofei Yu Haofei Yu Weiyan Hu Weiyan Hu |
| author_facet | Kunying Zhao Kunying Zhao Yuxiao Zhang Yuxiao Zhang Shuda Yang Shuda Yang Lirong Xiang Lirong Xiang Shangpeng Wu Shangpeng Wu Junfang Dong Junfang Dong Huan Li Huan Li Haofei Yu Haofei Yu Weiyan Hu Weiyan Hu |
| author_sort | Kunying Zhao |
| collection | DOAJ |
| description | Major depressive disorder (MDD) is one of the most common mental health conditions, characterized by pervasive and persistent low mood, low self-esteem, and a loss of interest or pleasure in activities that are typically enjoyable. Despite decades of research into the etiology and pathophysiological mechanisms of depression, the therapeutic outcomes for many individuals remain less than expected. A promising new area of research focuses on stress-induced neuroinflammatory processes, such as the excessive activation and crosstalk of microglia and astrocytes in the central nervous system under stress, as well as elevated levels of pro-inflammatory cytokines, which are closely linked to the onset and progression of depression. This review summarizes the mechanisms through which neuroinflammation induces or promotes the development of depression, and also highlights the effective roles of small molecules with anti-inflammatory activity in the treatment of MDD. Understanding the specific mechanisms through which stress-induced neuroinflammation further impacts depression, and using technologies such as single-cell RNA sequencing to elucidate the specific subtypes and interactions of microglia and astrocytes in depression, is of great importance for developing more effective therapeutic strategies for MDD. |
| format | Article |
| id | doaj-art-ea310054965344e18da2abc7911095c3 |
| institution | DOAJ |
| issn | 1662-5102 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj-art-ea310054965344e18da2abc7911095c32025-08-20T03:14:46ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022025-04-011910.3389/fncel.2025.15380261538026Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implicationsKunying Zhao0Kunying Zhao1Yuxiao Zhang2Yuxiao Zhang3Shuda Yang4Shuda Yang5Lirong Xiang6Lirong Xiang7Shangpeng Wu8Shangpeng Wu9Junfang Dong10Junfang Dong11Huan Li12Huan Li13Haofei Yu14Haofei Yu15Weiyan Hu16Weiyan Hu17School of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaCollege of Modern Biomedical Industry, Kunming Medical University, Kunming, ChinaMajor depressive disorder (MDD) is one of the most common mental health conditions, characterized by pervasive and persistent low mood, low self-esteem, and a loss of interest or pleasure in activities that are typically enjoyable. Despite decades of research into the etiology and pathophysiological mechanisms of depression, the therapeutic outcomes for many individuals remain less than expected. A promising new area of research focuses on stress-induced neuroinflammatory processes, such as the excessive activation and crosstalk of microglia and astrocytes in the central nervous system under stress, as well as elevated levels of pro-inflammatory cytokines, which are closely linked to the onset and progression of depression. This review summarizes the mechanisms through which neuroinflammation induces or promotes the development of depression, and also highlights the effective roles of small molecules with anti-inflammatory activity in the treatment of MDD. Understanding the specific mechanisms through which stress-induced neuroinflammation further impacts depression, and using technologies such as single-cell RNA sequencing to elucidate the specific subtypes and interactions of microglia and astrocytes in depression, is of great importance for developing more effective therapeutic strategies for MDD.https://www.frontiersin.org/articles/10.3389/fncel.2025.1538026/fulldepressionneuroinflammationmicrogliaastrocytesanti-inflammatory |
| spellingShingle | Kunying Zhao Kunying Zhao Yuxiao Zhang Yuxiao Zhang Shuda Yang Shuda Yang Lirong Xiang Lirong Xiang Shangpeng Wu Shangpeng Wu Junfang Dong Junfang Dong Huan Li Huan Li Haofei Yu Haofei Yu Weiyan Hu Weiyan Hu Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications Frontiers in Cellular Neuroscience depression neuroinflammation microglia astrocytes anti-inflammatory |
| title | Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications |
| title_full | Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications |
| title_fullStr | Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications |
| title_full_unstemmed | Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications |
| title_short | Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications |
| title_sort | neuroinflammation and stress induced pathophysiology in major depressive disorder mechanisms and therapeutic implications |
| topic | depression neuroinflammation microglia astrocytes anti-inflammatory |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2025.1538026/full |
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