Hold the salt: gut reaction may impair the brains of mice

In a new mouse study, scientists link changes in the gut caused by a high-salt diet to impaired blood flow in the brain. This reduced blood flow can eventually lead to impaired cognition that could be reversed by changing back to a normal diet.

A high-salt diet in mice can increase the number of immune cells releasing IL17 (green), which can negatively affect blood flow in the brain. Image credit: Iadecola lab, Weill Cornell Medicine, New York City

In this study, mice were fed a high-salt diet (HSD) containing 16 times the amount of sodium chloride typically found in their food. After eight weeks, their brains showed a 20 to 30 percent reduction in blood flow compared to mice that ate normal food.

This drop in blood flow was accompanied by the appearance of dementia-like symptoms, including defects in the ability of HSD mice to recognize objects, navigate a maze, and properly build a nest. When the mice were returned to a normal diet, both blood flow and cognition improved, suggesting that the negative effects of excessive salt consumption could be reversible.

To study further how salt affects blood flow in the brain, blood vessels were taken from the brains of mice fed a high-salt diet and grown in a dish. Normally, these vessels tighten (constrict) to reduce blood flow or relax (dilate) to increase flow.

However, those taken from HSD mice did not dilate properly when stimulated to do so. A closer look revealed a reduction in the function of the enzyme eNOS that is responsible for producing nitric oxide (NO), a potent signal for blood vessels to dilate.

When the amino acid L-arginine, which can increase eNOS activity and NO production, was added to the dishes containing blood vessels from HSD mice, the cells responded normally. When L-arginine was injected into HSD mice directly, the defects in cognition were also rescued.

These findings together show that a high-salt diet affects the activity of the eNOS enzyme, which in turn leads to problems with blood flow and cognition.

But the question still remained how the ingestion of salt could lead to these effects in the brain.

One clue came from evidence showing that eating high levels of salt changes the immune system of the gut, a finding that was first reported by scientists studying salt’s effects in a model of multiple sclerosis. Specifically, a high-salt diet increased the appearance of TH17 immune cells. These TH17 cells secrete a molecule, IL-17, that can have toxic effects on blood vessels.

Because the researchers did not observe any TH17 cells in the brains of HSD mice, they concluded that it must be IL-17, moving throughout the circulatory system, that was acting directly on the brain’s blood vessels. (National Institutes of Health)

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