neurosciencestuff: (Image caption: White blood cells that…


(Image caption:
White blood cells that produce a protein called IL-17 (green)
accumulate in large numbers in the small intestine of mice fed a
high-salt diet for eight weeks (right), compared with mice fed a normal
diet. This magnified image shows cells in a part of the intestinal layer
that absorbs digested food and protects against infection. Photo
credit: The Iadecola Lab)

A High-Salt Diet Produces Dementia in Mice

A high-salt diet reduces resting blood flow to the brain and causes
dementia in mice, according to a new study by scientists from Weill
Cornell Medicine.

The study,
published Jan.15 in Nature Neuroscience, is the first to unveil a
gut-brain connection linking high dietary salt intake to neurovascular
and cognitive impairment. The findings illuminate a potential future
target for countering harmful effects to the brain caused by excess salt

“We discovered that mice fed a high-salt diet developed dementia even when blood pressure did not rise,” said senior author Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute
(BMRI) and the Anne Parrish Titzell Professor of Neurology at Weill
Cornell Medicine. “This was surprising since, in humans, the deleterious
effects of salt on cognition were attributed to hypertension.”

A vast majority, about 90 percent of American adults, consume more dietary sodium than the recommended 2,300 mg per day.  

mice were given food containing 4 percent or 8 percent salt,
representing an 8- to 16-fold increase in salt compared to a normal
mouse diet. The higher level was comparable to the high end of human
salt consumption. After eight weeks, the scientists examined the mice
using magnetic resonance imaging. The mice showed marked reductions in
resting cerebral blood flow in two areas of the brain involved in
learning and memory: 28 percent decrease in the cortex and 25 percent in
the hippocampus.

The scientists discovered that an impaired
ability of cells lining blood vessels, called endothelial cells, reduced
the production of nitric oxide, a gas normally produced by the
endothelial cells to relax blood vessels and increase blood flow. To see
if the biological effects of a high-salt diet could be reversed, Dr.
Iadecola and colleagues returned some mice to a regular diet for four
weeks and found that cerebral blood flow and endothelial function
returned to normal.

Rodents that only ate the high-salt diet
developed dementia, performing significantly worse on an object
recognition test, a maze test and nest building—a typical activity of
daily living for mice, spending less time building nests and using much
less nesting material than normal mice.

Next, the scientists
performed several experiments to understand the biological mechanisms
connecting high salt intake with dementia. They discovered that the mice
developed an adaptive immune response in their guts, with increased
activity of a subset of white blood cells that play an important role in
the activity of other immune cells. The increase in those white blood
cells, T helper lymphocytes called TH17, boosted the production of a
protein called interleukin 17 (IL-17) that regulates immune and
inflammatory responses, causing a reduction in the production of nitric
oxide in endothelial cells.

In a final experiment, the scientists
treated the mice with a drug known to prevent the suppression of nitric
oxide activity, called ROCK inhibitor Y27632. The drug reduced
circulating levels of IL-17 and the mice showed improved behavioral and
cognitive functions, said Dr. Iadecola, who is on the strategic advisory
board and receives a consulting fee from Broadview Ventures Inc.
Broadview Ventures Inc. was created by the board of the Foundation
Leducq Trust, the supporting trust of Foundation Leducq.

IL-17-ROCK pathway is an exciting target for future research in the
causes of cognitive impairment,” said Dr. Giuseppe Faraco, assistant
professor of research in neuroscience in the BMRI and first author of
the study. “It appears to counteract the cerebrovascular and cognitive
effects of a high-salt diet, and it also may benefit people with
diseases and conditions associated with elevated IL-17 levels, such as
multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and
other autoimmune diseases.”

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