Eating too much salt may contribute to depression

You might already know that salty food affects your blood pressure. But a new study suggests it could be doing something far more surprising – it might be changing how you feel. Scientists have now linked high salt intake to depression-like behavior, revealing a new immune mechanism that connects the gut, the brain, and mood.

The study, led by researchers from Nanjing Medical University explored how excess salt changes the immune system in ways that alter brain function and behavior.

The findings are built on years of clinical observations that hinted at a connection between high-sodium diets and worsening mental health. Now, there is experimental evidence to back it.

“This work supports dietary interventions, such as salt reduction, as a preventive measure for mental illness. It also paves the way for novel therapeutic strategies targeting IL-17A to treat depression,” said Dr. Xiaojun Chen, the study’s lead researcher.

“We hope these findings encourage discussions on salt consumption guidelines.”

How salt leads to depression

The researchers noticed that mice on a high-salt diet for five weeks showed less curiosity and more inactivity. These behaviors resembled those seen in standard stress-based models of depression.

Mice with high salt intake also showed elevated IL-17A levels in the spleen, blood, and brain – especially the hippocampus and prefrontal cortex.

IL-17A was not just present; it was active. In mice lacking the RORγt gene – a gene required for IL-17A production – these depressive symptoms did not appear. This points to a direct causal link between IL-17A and mood changes triggered by salt.

Special immune cells trigger mood changes

The research also pinpointed γδT17 cells as the key producers of IL-17A. These cells made up nearly 40% of IL-17A producers in the spleen, blood, and brain. Their activity increased in the high-salt group, but the total number of γδT cells stayed the same. Instead, the shift was in their function, not quantity.

Specifically, HSD triggered γδT cells to become hyperactive IL-17A producers, marked by higher CD44 expression and a tilt toward the Vγ4 subtype. These cells likely carry out the salt-triggered immune attack on the brain, altering mood and behavior.

Blocking salt-linked cells eases depression

To investigate further, scientists treated mice with antibodies that deplete γδT cells. This lowered IL-17A levels and reversed depression-like behavior. The mice explored more and spent less time immobile in behavioral tests. These results highlight γδT17 cells as potential drug targets.

Interestingly, combining salt with restraint stress did not worsen depression in the same way. This suggests that salt may trigger a different biological route to depression than psychological stress.

Salt alters immunity and metabolism

The team also proposed two possible molecular pathways. First, HSD may activate the p38/MAPK pathway in γδT cells, increasing IL-17A output.

Second, salt might raise IL-1β levels in macrophages. IL-1β is a known driver of IL-17 production. Both routes could explain how salt tweaks immune function and mood.

Salt also affects how immune cells make energy. By shifting cells from mitochondrial respiration to glycolysis, HSD reprograms how immune cells behave. These metabolic shifts might further activate γδT17 cells, linking diet and mood through immune cell energy use.

What this means for mental health

Major depressive disorder is already a leading cause of disability and death. Its ties to other diseases, like cancer and autoimmune conditions, make it an urgent health issue. Treatments that target immune signals, especially IL-17A, could provide new hope.

The research confirms what some clinical data hinted at: high salt worsens depression, while low sodium intake improves mood. Dietary advice could now go beyond blood pressure and heart health. It may become a mental health intervention too.

Next steps and broader impacts

The researchers will now try to validate these results in human studies.

If confirmed, simple dietary changes could lower depression risk. Drugs that block IL-17A or deactivate γδT cells might also help people with salt-sensitive mood disorders.

This study not only challenges how we view diet and mood but also shows how tightly the immune system and brain work together. What we eat might shape how we feel – cell by cell, molecule by molecule.

The study is published in The Journal of Immunology.

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