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February 9, 2018
Digest
Hold the Salt: Gut Reaction May Impair the Brains of Mice

We are often warned of the dangers of high levels of salt in our diet, yet the risks of salt consumption and the effects of salt on the body, including the brain, are not entirely clear. 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. The study, published in Nature Neuroscience, also provides molecular clues for treating these problems.

A new mouse study links changes in the gut caused by a high-salt diet to impaired blood flow in the brain.
A new mouse study links changes in the gut caused by a high-salt diet to impaired blood flow in the brain.

IMAGE: PIXHOOK/ISTOCK

“For years researchers have wondered how a high-salt diet harms the brain,” said Dr. Jim Koenig, program director at NINDS, which supported the study. “This mouse study provides a detailed cellular and molecular diagram for how the problems start in the gut and opens unexpected paths towards new treatments.”

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 8 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.

“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,” said Dr. Costantino Iadecola, director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City and senior author of the study.

In humans, high levels of salt in the diet has long been associated with high blood pressure, and increasing evidence has linked blood pressure and brain health. However, the blood pressure of HSD mice was not affected, suggesting a very specific and independent mechanism for the changes seen here.

“This study adds to our growing understanding of how the gut can modulate brain function,” said Koenig. “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.”

Memory Gene Goes Viral

Two independent teams of scientists from the University of Utah and the University of Massachusetts Medical School have discovered that a gene crucial for learning, called Arc, can send its genetic material from one neuron to another by employing a strategy commonly used by viruses.

NIH-funded studies have unveiled a new way that nervous system cells interact.
NIH-funded studies have unveiled a new way that nervous system cells interact.

IMAGE: KIRSTY PARGETER/THINKSTOCK

The studies, both published in Cell, unveil a new way that nervous system cells interact.

“This work is a great example of the importance of basic neuroscience research,” said Dr. Edmund Talley, a program director at NINDS. “What began as an effort to examine the behavior of a gene involved in memory and implicated in neurological disorders such as Alzheimer’s disease has unexpectedly led to the discovery of an entirely new process, which neurons may use to send genetic information to one another.”

While Arc is known to play a vital role in the brain’s ability to store new information, little is known about precisely how it works. In addition, previous studies had detailed similarities between the Arc protein and proteins found in certain viruses like HIV, but it was unclear how those commonalities influenced the behavior of the Arc protein.

The University of Utah researchers began their examination of the Arc gene by introducing it into bacterial cells. To their surprise, when the cells made the Arc protein, it clumped together into a form that resembled a viral capsid, the shell that contains a virus’s genetic information. The Arc “capsids” appeared to mirror viral capsids in their physical structure as well as their behavior and other properties.

“Beforehand, if I had said to any neuroscientist that this gene sort of acts like a virus, they would have laughed at me,” said Dr. Jason Shepherd, an assistant professor at the University of Utah. “We knew this was going to take us in a completely new direction.

“This research highlights the fact that we often don’t know where the cool discoveries are going to come from,” he added. “We need to follow where the science takes us.”

NIH Scientists Find Microbes on The Skin of Mice Promote Tissue Healing, Immunity

Beneficial bacteria on the skin of lab mice work with the animals’ immune systems to defend against disease-causing microbes and accelerate wound healing, according to new research from NIAID scientists.

Researchers say untangling similar mechanisms in humans may improve approaches to managing skin wounds and treating other damaged tissues. The study was published online Jan. 18 in Cell.

Like humans and other mammals, mice are inhabited by large, diverse microbial populations collectively called the microbiome. While the microbiome is believed to have many beneficial functions across several organ systems, little is known about how the immune system responds to these harmless bacteria.

To investigate, NIAID scientists led by Dr. Yasmine Belkaid, chief of the mucosal immunology section of the Laboratory of Parasitic Diseases, observed the reaction of mouse immune cells to Staphylococcus epidermidis, a bacterium regularly found on human skin that does not normally cause disease. To their surprise, immune cells recognized S. epidermidis using evolutionarily ancient molecules called non-classical MHC molecules, which led to the production of unusual T cells with genes associated with tissue healing and antimicrobial defense.

In contrast, immune cells recognize disease-causing bacteria with classical MHC molecules, which lead to the production of T cells that stoke inflammation.

Researchers then took skin biopsies from two groups of mice—one group that had been colonized by S. epidermidis and another that had not.

Over 5 days, the group that had been exposed to the beneficial bacteria experienced more tissue repair at the wound site and less evidence of inflammation.

Belkaid’s team plans to next probe whether non-classical MHC molecules recognize friendly microbes on the skin of other mammals, including humans, and similarly benefit tissue repair. Eventually, mimicking the processes initiated by the microbiome may allow clinicians to accelerate wound healing and prevent dangerous infections, the researchers note.

Zika Infection During Pregnancy May Disrupt Fetal Oxygen Supply

Zika virus infection appears to affect oxygen delivery to the fetuses of pregnant monkeys, according to a small study funded by NIH. Researchers also observed a high degree of inflammation in the placenta and lining of the uterus, which can harm the fetal immune system and increase a newborn’s susceptibility to additional infections. The study is published online in Nature Communications.

Zika virus infection among pregnant women can lead to developmental problems in fetuses and newborns.
Zika virus infection among pregnant women can lead to developmental problems in fetuses and newborns.

IMAGE: ISTOCK

Zika virus infection among pregnant women can lead to developmental problems in fetuses and newborns. In the current study, researchers led by Dr. Daniel Streblow of the Vaccine & Gene Therapy Institute at Oregon National Primate Research Center, used non-invasive imaging to evaluate how persistent Zika infection affects pregnancy in five rhesus macaques. The team found that the virus induces high levels of inflammation in the blood vessels of the uterus and damages placental villi, the branch-like growths that help transfer oxygen and nutrients from maternal blood to the fetus. The researchers suggest that this damage may disrupt oxygen transport to the fetus, which can restrict its growth and lead to stillbirth, among other conditions.

The team observed evidence of fetal brain abnormalities in 2 of the 5 animals, but the researchers did not see any obvious signs of microcephaly. This finding, they reason, is consistent with previous studies that establish microcephaly as only one of a spectrum of Zika-induced complications. The authors call for additional studies to improve knowledge of how Zika virus causes infection during pregnancy.

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