Pass the salt: Mapping the neurons that drive salt cravings

D.+Sodium+intake+Just+as+thirst+stimulates+water+intake,+salt+craving+triggers+a+need+to+ingest+NaCl..jpgWhile the average American’s high-salt diet has been linked to high blood pressure and cardiovascular disease, the truth is we couldn’t live without this once scarce mineral. Salt helps the body balance its water content and plays a critical role in regulating blood pressure and cellular function throughout the body. As salt is lost through excretion and other metabolic processes, hormones are released in response to sodium deficiency. However, exactly how these hormones work on the brain to trigger salt-seeking and salt-consuming behavior has remained a mystery.

Now, a team of scientists in the Division of Endocrinology, Diabetes and Metabolism at Beth Israel Deaconess Medical Center (BIDMC), have shed new light on the process. In research published (September, 2017) in the journal Neuron, a team of scientists working in the lab of Bradford Lowell, MD, PhD, identified the sub-population of neurons that respond to the body’s sodium deficiency and mapped the brain circuitry underlying the drive to consume salt. “We identified a specific circuit in the brain that detects sodium deficiency and drives an appetite specific for sodium to correct the deficiency,” said co-first author Jon M. Resch, PhD, a post-doctoral fellow in Lowell’s lab. “In addition, this work establishes that sodium ingestion is tightly regulated by the brain, and dysfunction in these neurons could lead to over or under consumption of sodium, which could lead to stress on the cardiovascular system over time.”

The team focused on a subset of neurons, known as NTSHSD2, discovered a decade ago by co-corresponding author, Joel Geerling, MD, PhD, formerly of BIDMC and now assistant professor in the Department of Neurology at Carver College of Medicine at the University of Iowa. In a series of experiments in sodium-deficient mice, the researchers demonstrate that sodium deficiency activates these neurons. They also showed that the presence of the hormone aldosterone, which the body releases during sodium deficiency, increases the neurons’ response. “These neurons appear to be highly influenced by these hormones and less so by inputs from other neurons — though further study is warranted,” said Resch. “This is a unique and very unexpected feature of these NTSHSD2 neurons.”

The researchers also revealed that NTSHSD2 neurons, located in a part of the brain called the nucleus of the solitary tract, are not solely responsible for driving the sodium appetite. In experiments using mice not deficient in sodium, artificial activation of NTSHSD2 neurons triggered sodium consumption only when there was also concurrent signaling by angiotensin II, a hormone also released by the body during sodium deficiency. From this, Resch and colleagues concluded that another set of neurons sensitive to angiotensin II likely plays a role in driving sodium appetite. These neurons have yet to be identified.

The findings demonstrated that only a synergistic relationship between the two distinct sub-populations of neurons that respond to aldosterone and angiotensin II can cause the rapid and robust onset of the sodium appetite seen in the experimentally deficient mice. Resch notes the sodium-appetite circuity he and colleagues have revealed provides a physiological framework for a hypothesis put forth in the early 1980s. “Several questions remain with regard to how sodium appetite works, but a major one is where ATII is acting in the brain and how the signal works in concert with NTSHSD2 neurons that respond to aldosterone,” he said. “We have already begun work to help us close these gaps in our knowledge.”

Adapted from: Jon M. Resch, Henning Fenselau, Joseph C. Madara, Chen Wu, John N. Campbell, Anna Lyubetskaya, Brian A. Dawes, Linus T. Tsai, Monica M. Li, Yoav Livneh, Qingen Ke, Peter M. Kang, Géza Fejes-Tóth, Anikó Náray-Fejes-Tóth, Joel C. Geerling, Bradford B. Lowell. Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling. Neuron, 2017; 96 (1): 190 DOI: 10.1016/j.neuron.2017.09.014

Nutrition Tip of the Day

Make it fun for kids to try new fruits and vegetables! Let them pick out a new fruit or vegetable in the grocery store each week, and figure out together how to cook or prepare it in a healthy way.

Daily Inspiration 

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Nerves control the body’s bacterial community

 

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A central aspect of life sciences is to explore the symbiotic cohabitation of animals, plants and humans with their specific bacterial communities. Scientists refer to the full set of microorganisms living on and inside a host organism as the microbiome. Over the past years, evidence has accumulated that the composition and balance of this microbiome contributes to the organism’s health. For instance, alterations in the composition of the bacterial community are implicated in the origin of various so-called environmental diseases. However, it is still largely unknown just how the cooperation between organism and bacteria works at the molecular level and how the microbiome and body exactly act as a functional unit.

An important breakthrough in deciphering these highly complex relationships has now been achieved by a research team from Kiel University’s Zoological Institute. Using the freshwater polyp Hydra as a model organism, the Kiel-based researchers and their international colleagues investigated how the simple nervous system of these animals interacts with the microbiome. They were able to demonstrate, for the first time, that small molecules secreted by nerve cells help to regulate the composition and colonization of specific types of beneficial bacteria along the Hydra’s body column. “Up to now, neuronal factors that influence the body’s bacterial colonization were largely unknown. We have been able to prove that the nervous system plays an important regulatory role here,” emphasizes Professor Thomas Bosch, evolutionary developmental biologist and spokesperson of the Collaborative Research Centre 1182 “Origin and Function of Metaorganisms,” funded by the German Science Foundation (DFG). The scientists published their new findings in Nature Communications (September 2017).

The research team, led by Bosch, used the freshwater polyp Hydra as the model organism to elucidate the fundamental principles of nervous system structure and function. Hydra represent an evolutionary ancient branch of the animal kingdom; they have a simple body plan with a nerve net of only about 3000 neurons. Applying modern experimental technology to these organisms that, despite their simplicity, still share a large molecular similarity with the nervous systems of vertebrates, enabled identification of ancient and therefore fundamental principles of nervous system structure and function. Using this model organism, the researchers from Kiel University addressed the question of how messenger substances produced by the nervous system, known as neuropeptides, control the cooperation and communication between host and microbes. They collected cellular, molecular and genetic evidence to show that neuropeptides have antibacterial activity which affects both the composition and the spatial distribution of the colonizing microbes.

To reveal the connections between neuropeptides and bacterial communities, the Kiel-based researchers first concentrated on the development of the freshwater polyp’s nervous system, from the egg stage to an adult animal. Cnidarians develop a complete nervous system within about three weeks. During this developmental time, the bacterial communities covering the animal’s surface change radically, until a stable composition of the microbiome finally forms. Under the influence of the antimicrobial effect of the neuropeptides, the concentration of so-called Gram-positive bacteria, a subgroup of bacteria, decreases sharply over a period of roughly four weeks. At the end of the maturing process, a typical composition of the microbiome prevails, particularly dominated by Gram-negative Curvibacter bacteria. Since the neuropeptides are particularly produced in certain areas of the body only, they also control the spatial localization of the bacteria along the body column. Therefore, in the head region, for example, there is a strong concentration of antimicrobial peptides, resulting in six times fewer Curvibacter bacteria than on the tentacles.

Based on these observations, the scientists concluded that throughout the course of evolution the nervous system also participated in a controlling role for the microbiome, in addition to its sensory and motor tasks. “The findings are also important in an evolutionary context. Since the ancestors of these animals have invented the nervous system, it seems that the interaction between the nervous system and the microbiome is an ancient feature of multicellular animals. Since the simple design of Hydra has great basic and translational relevance and promises to reveal new and unexpected basic features of nervous systems, further research into the interaction between body and bacteria will therefore concentrate more on the neuronal aspects,” said Bosch, to summarize the significance of the work.

Adapted from: Kiel University. (2017, September 26). Nerves control the body’s bacterial community: Research team proves, for the first time, that there is close cooperation between the nervous system and the microbial population of the body. ScienceDaily. Retrieved December 20, 2017 from http://www.sciencedaily.com/releases/2017/09/170926105425.htm

Nutrition Tip of the Day

Keep a food diary! Most people don’t realize how much they really consume in a day. If you write it down, the amount you eat may surprise you.

Daily Inspiration 

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