“A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia, but it remains unclear how dietary salt harms the brain,” according to the study. “We report that, in mice, excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment.”
In the study funded by the National Institutes of Health and published Monday, mice were given 16 times the amount of sodium chloride normally found in their food as part of a high-salt diet.
After eight weeks, the mice began to show a 20 to 30 percent decrease in brain blood flow accompanied by dementia-like symptoms compared to mice that were given a regular diet.
The dementia-like symptoms included a decrease in the ability of mice to recognize objects, navigate a maze and properly build a nest.
Researchers found that blood vessels extracted from the brains of mice on the high-salt diet failed to properly dilate when stimulated, revealing a reduction in the function of the enzyme eNOS that produces nitric oxide (NO), which serves as a signal for blood vessels to dilate.
The amino acid L-arginine, which has the ability to increase activity of the eNOS enzyme and NO production, caused the mice’s isolated blood vessels to respond normally and reversed cognition deficiencies when injected directly into the mice, according to the study.
However, the study also suggests the negative effects of excessive salt consumption can be reversed with a return to a regular diet, as evidence shows both blood flow and cognition improved in the mice who were taken off the high-salt diet.
To explain how the ingestion of salt could lead to such effects on the brain, researchers cited evidence that eating high levels of salt changes the immune system of the gut.
Specifically, a diet high in salt can increase TH17 immune cells that emit the molecule IL-17, which can have negative effects on blood vessels. Due to an absence of TH17 cells observed in mice on the high-salt diet, scientists found that IL-17 directly affects the brain’s blood vessels as it makes its way throughout the circulatory system.
Three other experiments were done to help confirm the hypothesis, according to the National Institutes of Health.
The study’s lead author, Dr. Costantino Iadecola, director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said in a statement that the brain “is extremely dependent on getting the right amount of blood at the right time.”
“If blood flow isn’t matched to what the brain needs, things go wrong,” Iadecola said.
Dr. Jim Koenig, program director at the National Institute of Neurological Disorders and Stroke, which is part of the National Institutes of Health, said the mouse study “provides a detailed cellular and molecular diagram for how the problems start in the gut and opens unexpected paths towards new treatments.”
“This study adds to our growing understanding of how the gut can modulate brain function,” Koenig said in a statement. “From a public health perspective, the fact that these effects can be reversed by halting the ingestion of salt is very important and could help us improve health in areas where many people eat a high-salt diet.”
The study was funded by grants from the National Institutes of Health, American Heart Association and the Paris-based Fondation Leducq.
Next, Iadecola and his colleagues plan to explore how lower NO production and blood flow levels cause cognition changes.