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ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition, Psychology and Brain Health
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1470505
This article is part of the Research Topic The Foundational Components and Elements of Plant Foods for Neurological Nutrition and Well-being View all articles
MgSO4 alleviates hippocampal neuroinflammation and BBB damage to resist CMS-induced depression
Provisionally accepted
Chuanfeng Tang 1*
Qiaona Wang 2 Yuefeng Hu 3 Liyun Hu 3 Fan Li 3 Yizhu Zhang 1 Yunfa Qiao 2 Renlei Wang 2,4*- 1 Nanjing University of Chinese Medicine, Nanjing, China
- 2 Nanjing University of Information Science and Technology, Nanjing, Jiangsu Province, China
- 3 Nanjing Normal University, Nanjing, Jiangsu Province, China
- 4 Jiangsu Second Normal University, Nanjing, Jiangsu Province, China
Purpose Magnesium sulfate (MgSO4) possesses the advantages of being readily accessible, cost-effective, and having low toxicity. It has potential applications as a neuroprotective agent. The mechanisms underlying the effects of Mg 2+ treatment on depression and its neuroprotective properties remain poorly elucidated.In this study, we employed chronic mild unpredictable stress (CMS)-induced mice were orally administered with MgSO4 or pioglitazone. The CMS-induced depressive-like behaviors of mice were monitored. After sacrifice, the levels of Mg 2+ and inflammatory cytokines were observed. Blood-brain barrier (BBB) permeability and the M1-to-M2 shift of microglia in mouse hippocampus were detected. The expression of proteins in IKK/NF-κB and NLRP3 inflammasome signal pathway were analyzed.We found that CMS induced depressive-like behaviors as well as hypomagnesemia in mice, which were accompanied with hypersecretion of inflammatory cytokines in hippocampus of mice. These animals induced by CMS exhibited hippocampal neuroinflammation characterized by an elevated number of Iba + microglia with enlarged cell bodies and increased branching structures. In CMS-induced mice, MgSO4 alleviated CMS-induced depressive-like behaviors and hypomagnesemia, reduced the levels of inflammatory cytokines in both serum and hippocampus, decreased the number of Iba + microglia, modulated microglia polarization and repaired the BBB damage. MgSO4 also significantly facilitates the M1to-M2 shift in CMS-induced mouse hippocampus and lipopolysaccharide (LPS)induced BV2 microglia. Mechanically, we found that MgSO4 inhibited microglia activation and BBB damage, possibly by suppressing IKK/NF-κB and NLRP3 inflammasome signaling pathways. 3 Conclusion Our findings showed that MgSO4 supplementation played an active role in the prevention and treatment of depression.
Keywords: CMS, MgSO4, Hippocampal neuroinflammation, Blood-Brain Barrier, Depression
Received: 25 Jul 2024; Accepted: 10 Mar 2025.
Copyright: © 2025 Tang, Wang, Hu, Hu, Li, Zhang, Qiao and Wang. 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:
Chuanfeng Tang, Nanjing University of Chinese Medicine, Nanjing, China
Renlei Wang, Nanjing University of Information Science and Technology, Nanjing, 210044, Jiangsu Province, China
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