High-salt diet promotes cognitive impairment through the Alzheimer-linked protein tau
New study in Nature finds that a high-salt diet may negatively affect cognitive function in pre-clinical setting
October 23, 2019
Science Daily/Weill Cornell Medicine
Investigators sought to understand the series of events that occur between salt consumption and poor cognition and concluded that lowering salt intake and maintaining healthy blood vessels in the brain may 'stave off' dementia. Accumulation of tau deposits has been implicated in the development of Alzheimer's disease in humans.
A high-salt diet may negatively affect cognitive function by causing a deficiency of the compound nitric oxide, which is vital for maintaining vascular health in the brain, according to a new study in mice from Weill Cornell Medicine researchers. When nitric oxide levels are too low, chemical changes to the protein tau occur in the brain, contributing to dementia.
In the study, published Oct. 23 in Nature, the investigators sought to understand the series of events that occur between salt consumption and poor cognition and concluded that lowering salt intake and maintaining healthy blood vessels in the brain may "stave off" dementia. Accumulation of tau deposits has been implicated in the development of Alzheimer's disease in humans.
"Our study proposes a new mechanism by which salt mediates cognitive impairment and also provides further evidence of a link between dietary habits and cognitive function," said lead study author Dr. Giuseppe Faraco, an assistant professor of research in neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine.
The new study builds upon research published last year in Nature Neuroscience by Dr. Faraco and senior author Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute and the Anne Parrish Titzell Professor of Neurology at Weill Cornell Medicine.
The 2018 study found that a high-salt diet caused dementia in mice. The rodents became unable to complete daily living tasks such as building their nests and had problems passing memory tests. The research team determined that the high-salt diet was causing cells in the small intestine to release the molecule interleukin-17 (IL-17), which promotes inflammation as part of the body's immune response.
IL-17 then entered the bloodstream and prevented the cells in the walls of blood vessels feeding the brain from producing nitric oxide. This compound works by relaxing and widening the blood vessels, allowing blood to flow. Conversely, a shortage of nitric oxide can restrict blood flow.
Based on these findings, Dr. Iadecola, Dr. Faraco and their colleagues theorized that salt likely caused dementia in mice because it contributed to restricted blood flow to the brain, essentially starving it. However, as they continued their research, they realized that the restricted blood flow in mice was not severe enough to prevent the brain from functioning properly.
"We thought maybe there was something else going on here,'" Dr. Iadecola said. In their new Nature study, the investigators found that decreased nitric oxide production in blood vessels affects the stability of tau proteins in neurons. Tau provides structure for the scaffolding of neurons. This scaffolding, also called the cytoskeleton, helps to transport materials and nutrients across neurons to support their function and health.
"Tau becoming unstable and coming off the cytoskeleton causes trouble," Dr. Iadecola said, adding that tau is not supposed to be free in the cell. Once tau detaches from the cytoskeleton, the protein can accumulate in the brain, causing cognitive problems. The researchers determined that healthy levels of nitric oxide keep tau in check. "It puts the brakes on activity caused by a series of enzymes that leads to tau disease pathology," he said.
To further explore the importance of tau in dementia, the researchers gave mice with a high-salt diet and restricted blood flow to the brain an antibody to promote tau stability. Despite restricted blood flow, researchers observed normal cognition in these mice. "This demonstrated that's what's really causing the dementia was tau and not lack of blood flow," Dr. Iadecola said.
Overall, this study highlights how vascular health is important to the brain. "As we demonstrated, there's more than one way that the blood vessels keep the brain healthy," Dr. Iadecola said.
Although research on salt intake and cognition in humans is needed, the current mouse study is a reminder for people to regulate salt consumption, Dr. Iadecola said. "And the stuff that is bad for us doesn't come from a saltshaker, it comes from processed food and restaurant food," he said. "We've got to keep salt in check. It can alter the blood vessels of the brain and do so in vicious way."
https://www.sciencedaily.com/releases/2019/10/191023132201.htm
With beetroot juice before exercise, aging brains look 'younger'
April 19, 2017
Science Daily/Wake Forest University
Drinking a beetroot juice supplement before working out makes the brain of older adults perform more efficiently, mirroring the operations of a younger brain, according to a new study.
"We knew, going in, that a number of studies had shown that exercise has positive effects on the brain," said W. Jack Rejeski, study co-author. "But what we showed in this brief training study of hypertensive older adults was that, as compared to exercise alone, adding a beet root juice supplement to exercise resulted in brain connectivity that closely resembles what you see in younger adults."
While continued work in this area is needed to replicate and extend these exciting findings, they do suggest that what we eat as we age could be critically important to the maintenance of our brain health and functional independence.
Rejeski is Thurman D. Kitchin Professor and Director of the Behavioral Medicine Laboratory in the Department of Health & Exercise Science. The study, "Beet Root Juice: An Ergogenic Aid for Exercise and the Aging Brain," was published in the peer-reviewed Journals of Gerontology: Medical Sciences. One of his former undergraduate students, Meredith Petrie, was the lead author on the paper.
This is the first experiment to test the combined effects of exercise and beetroot juice on functional brain networks in the motor cortex and secondary connections between the motor cortex and the insula, which support mobility, Rejeski said.
The study included 26 men and women age 55 and older who did not exercise, had high blood pressure, and took no more than two medications for high blood pressure. Three times a week for six weeks, they drank a beetroot juice supplement called Beet-It Sport Shot one hour before a moderately intense, 50-minute walk on a treadmill. Half the participants received Beet-It containing 560 mg of nitrate; the others received a placebo Beet-It with very little nitrate.
Beets contain a high level of dietary nitrate, which is converted to nitrite and then nitric oxide (NO) when consumed. NO increases blood flow in the body, and multiple studies have shown it can improve exercise performance in people of various ages.
"Nitric oxide is a really powerful molecule. It goes to the areas of the body which are hypoxic, or needing oxygen, and the brain is a heavy feeder of oxygen in your body," said Rejeski.
When you exercise, the brain's somatomotor cortex, which processes information from the muscles, sorts out the cues coming in from the body. Exercise should strengthen the somatomotor cortex.
So, combining beetroot juice with exercise delivers even more oxygen to the brain and creates an excellent environment for strengthening the somatomotor cortex. Post-exercise analysis showed that, although the study groups has similar levels of nitrate and nitrite in the blood before drinking the juice, the beetroot juice group had much higher levels of nitrate and nitrite than the placebo group after exercise.
https://www.sciencedaily.com/releases/2017/04/170419091619.htm