Study identifies link between high-salt diet and depression

In this study, mice were fed a normal diet or HSD for 5 weeks, a common timeframe used to study excessive dietary salt intake. After five weeks, the mice fed the HSD showed less interest in exploring and more inactivity in various scenarios compared to mice fed a normal diet, suggesting depression-like symptoms in mice

Given the already established role of IL-17A in the development of depression, the research team also investigated whether HSD induced IL-17A production in mice. HSD increased IL-17A levels in the spleen, blood, and brain, correlating with anxiety- and depression-like behaviors. However, when mice that could not produce IL-17A were fed an HSD, depression-like symptoms were not observed, confirming the role of IL-17A in developing depression-like symptoms.

These findings corroborate epidemiological evidence that HSD correlates strongly with more severe depression and studies in people demonstrating that low sodium intake is closely associated with good mood.

The researchers hope these findings encourage further research into immune-mediated mechanisms of depression and pave the way for novel therapeutics targeting IL-17A or γδT cells. Dr. Chen and their team plan to validate these findings in humans while also investigating the mechanisms by which HSD activates γδT17 cells leading to increased HSD.  

Reference:

Di Lu, Wenjie Chen, Wenhui Sun, Chuan Wei, Xuan Xie, Na Li, Haiyan Yan, Ying Chen, Yue Wu, Zhigang Lei, Lei Xu, Jifeng Zhu, Yalin Li, Chuan Su, Wei Li, Sha Zhou, Xiaojun Chen, High-salt diet drives depression-like behavior in mice by inducing IL-17A production, The Journal of Immunology, 2025;, vkaf019, https://doi.org/10.1093/jimmun/vkaf019.