Science Tips: Two Updates from the Weizmann Institute of Science
STRESSING MATERIAL EXCHANGE
A receptor in the brain is found to regulate stress responses differently in male and female mice
How does stress, which, among other things, causes our bodies to divert resources from non-essential functions, affect the basic exchange of materials that underlies our everyday life? Weizmann Institute of Science researchers investigated this question by looking at a receptor in the brains of mice, and they came up with a surprising answer. The findings, which recently appeared in Cell Metabolism, may in the future aid in developing better drugs for stress-related problems and eating disorders.
Dr. Yael Kuperman began this study as part of her doctoral research in the lab of Prof. Alon Chen of the Neurobiology Department. Kuperman, presently a staff scientist in the Veterinary Resources Department, Chen and research student Meira Weiss focused on an area of the brain called the hypothalamus, which has a number of functions, among them helping the body adjust to stressful situations, controlling hunger and satiety, and regulating blood glucose and energy production.
When stress hits, cells in the hypothalamus step up production of a receptor called CRFR1. It was known that this receptor contributes to the rapid activation of a stress-response sympathetic nerve network – increasing heart rate, for example. But since this area of the brain also regulates the body’s exchange of materials, the team thought that the CRFR1 receptor might play a role in this, as well.
Chen and his group characterized the cells in a certain area of the hypothalamus, finding that the receptor is expressed in around half of those that arouse appetite and suppress energy consumption. These cells comprise one of two main populations in the hypothalamus – the second promotes satiety and burning energy. “This was a bit of a surprise,” says Kuperman, “as we would instinctively expect the receptor to be expressed on the cells that suppress hunger.”
To continue investigating, the researchers removed the CRFR1 receptor just from the cells that arouse appetite in the hypothalamus, in lab mice, and then observed how this affected their bodily functions. At first, they did not see any significant changes, confirming that this receptor is saved for stressful situations. When they exposed the mice to stress – cold or hunger – they got another surprise.
When exposed to cold, the sympathetic nervous system activates a unique type of fat called brown fat, which produces heat to maintain the body’s internal temperature. When the receptor was removed, the body temperature dropped dramatically – but only in the female mice. Even afterward their temperatures failed to stabilize, while male mice showed hardly any change.
Fasting produced a similarly drastic response in the female mice. Normally when food is scarce, the brain sends a message to the liver to produce glucose, conserving a minimum level in the blood. But when food was withheld from female mice missing the CRFR1 receptor, the amount of glucose their livers produced dropped significantly. In hungry male CRFR1-deficient mice, like those exposed to cold, the exchange of materials in their bodies was barely affected.
“We discovered that the receptor has an inhibitory effect on the cells, and this is what activates the sympathetic nervous system,” says Kuperman.
Among other things – revealing exactly how this receptor works and how it contributes to the stress response – the findings show that male and female bodies may exhibit significant differences in the ways that materials are exchanged under stress. Indeed, the fact that the receptor suppresses hunger in females may help explain why women are much more prone to eating disorders than men.
Because drugs can enter the hypothalamus with relative ease, the findings could be relevant to the development of treatments for regulating hunger or stress responses, including anxiety disorders or depression. Indeed, several pharmaceutical companies have already begun developing psychiatric drugs to block the CRFR1 receptor. The scientists caution, however, that because the cells are involved in the exchange of materials, blocking the receptor could turn out to have such side effects as weight gain.
Prof. Alon Chen’s research is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Perlman Family Foundation, Founded by Louis L. and Anita M. Perlman; the Adelis Foundation; the Irving I Moskowitz Foundation; European Research Council; the estate of Tony Bieber; and the Ruhman Family Laboratory for Research in the Neurobiology of Stress.
ÉCOLE POLYTECHNIQUE AND THE WEIZMANN INSTITUTE OF SCIENCE SIGN COOPERATION AGREEMENT
Jacques Biot, President of École Polytechnique (Palaiseau, France), and Prof. Daniel Zajfman, President of the Weizmann Institute of Science (Rehovot, Israel), signed a cooperation agreement to develop and promote collaboration in higher education and research between the two institutions.
With this agreement, École Polytechnique and the Weizmann Institute of Science, both renowned for their high standards of quality in academics and research, seek to promote the exchange of students and faculty members, as well as to foster scientific and academic cooperation in topics of common interest.
A laboratory-initiated collaboration
Prof. Victor Malka, Research Director at the Laboratory of Applied Optics, a joint laboratory of École Polytechnique, ENSTA ParisTech and CNRS, joined the Physics of Complex Systems Department of the Weizmann Institute of Science in October 2015. Malka is committed to bring École Polytechnique and WIS closer: “It felt natural to me to initiate this collaboration, to create scientific cooperation. Both presidents − of Polytechnique and the Weizmann Institute of Science − have fully endorsed this initiative, enabling its quick success.”
Malka’s research deals with laser-plasma accelerators. This accelerator concept, invented 30 years ago, has enabled researchers to obtain particle beams with unique properties. Very energetic, extremely bright and tunable in energy, these beams open new opportunities in such diverse fields such as medicine, chemistry, biology and materials science.
Recent improvements at the Laboratory of Applied Optics have opened the path to treating cancerous tumors. Research projects in this lab have yielded new perspectives, for example, on the detection of breast cancerous tumors at a very early stage. This new laser-plasma technology can also be used for industrial applications as it produces high-resolution, three-dimensional images of dense materials, for example those used in airplane parts.
Malka is currently working towards an association between the Laboratory of Applied Optics and the Weizmann Institute of Science Faculty of Physics to develop applications for laser-plasma accelerators. Under his initiative, two students from the Weizmann Institute of Science have already started PhD research at LOA.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 3,800 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
École Polytechnique is the leading French institute which combines top-level research, academics, and innovation at the cutting-edge of science and technology. Its various graduate-level programs – Ingénieur Polytechnicien, Master’s, Graduate Degree, PhD track and PhD – are highly selective and promote a culture of excellence with a strong emphasis on science, anchored in humanist traditions. As a widely internationalized university, École Polytechnique offers a variety of international programs and attracts a growing number of foreign students and researchers from around the globe (currently 30% of students and 39% of faculty members).
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The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. The Institute’s 3,800-strong scientific community engages in research addressing crucial problems in medicine and health, energy, technology, agriculture, and the environment. Outstanding young scientists from around the world pursue advanced degrees at the Weizmann Institute’s Feinberg Graduate School. The discoveries and theories of Weizmann Institute scientists have had a major impact on the wider scientific community, as well as on the quality of life of millions of people worldwide.
