Wednesday, May 04, 2022

Abnormal activity of brain circuit causes anorexia in animal model

BAYLOR COLLEGE OF MEDICINE

A team of researchers at Baylor College of Medicine, Louisiana State University and collaborating institutions has discovered that abnormal activity in a particular brain circuit underlies anorexia in an animal model of the condition. Genetically and pharmacologically restoring the normal activity of the brain circuit improved the condition, opening the possibility of developing a treatment strategy for affected individuals in the future. The study appears in Nature Neuroscience.

“Anorexia is an eating disorder. People affected are highly concerned about gaining weight and usually severely restrict the amount of food they eat and exercise excessively, which leads to severe weight loss. Anorexia has the highest mortality rate among all psychiatric diseases,” said lead author Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor. “The condition has no approved treatment and the underlying cause is unclear. In this study we worked with an animal model of the condition that mimics many of the characteristics we observe in people to investigate brain circuit alterations that could be involved in the condition.”

Previous work in the Xu lab and by other groups has shown that dysfunction of dopamine and serotonin neurons, which regulate feeding, is associated with individuals with anorexia. However, how these two populations of neurons in the brain contribute to the condition was not clear.

“First, we found that under normal conditions dopamine neurons do communicate with serotonin neurons, and we studied this interaction to determine how it regulates feeding,” Xu said.

The researchers found that the strength of the signal transmitted along the dopamine-serotonin brain circuit determined how much the animals would eat.

“When dopamine neurons fired a lower-frequency signal, for example, between 2 and 10 Hertz, the result was inhibition of the serotonin neurons and overeating behavior,” Xu explained. “On the other hand, when dopamine neurons fired at a higher frequency between 10 and 30 Hertz, the serotonin neurons were activated and this led to lack of feeding.”

The researchers then investigated whether the dopamine-serotonin circuit would play a role in the development or persistence of anorexia in a mouse model. They discovered that this brain circuit is super activated in the animal model, when compared to controls, providing an explanation for the animals’ lack of appetite and excessive exercising.

In addition, the team identified the dopamine receptor DRD1 as a key mediator of the hyperactivity of this circuit. Knocking out the DRD1 gene partially restored normal eating and exercise behaviors in the animals.

“The findings suggested that pharmacologically inhibiting the DRD1 receptor could also help reduce the circuit’s hyperactivity, an approach that could have clinical applications,” Xu said. “Indeed, we found that a drug that interferes with DRD1 receptor activity can effectively prevent anorexia and weight loss in the animal model. These findings support further studies toward developing a similar therapeutic approach for individual with anorexia.”

Anorexia is more common in females than in males, but the reason for this difference is not clear. “In future work we plan to look into what mediates the differences between males and females and try to understand the mechanism,” Xu said.

Other contributors to this work include Xing Cai, Hailan Liu, Bing Feng, Meng Yu, Yang He, Hesong Liu, Chen Liang, Yongjie Yang, Longlong Tu, Nan Zhang, Lina Wang, Na Yin, Junying Han, Zili Yan, Chunmei Wang, Pingwen Xu, Qi Wu, Qingchun Tong and co-corresponding author Yanlin He. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Louisiana State University and the University of Texas Health Science Center at Houston.

The investigators of this study were supported by grants from the NIH (NIH R01DK114279, R01DK109934, R21NS108091, R00 DK107008, R01 DK123098, P30 DK020595, K01DK119471, R01DK109194, R56DK109194, P01DK113954, R01DK115761, R01DK117281, R01DK120858 and P20 GM135002). Further support was provided by DOD (Innovative Grant W81XWH-19-PRMRP-DA), the Pew Charitable Trust awards (0026188), Baylor Collaborative Faculty Research Investment Program grants, USDA/CRIS (51000-064-01S) and the American Diabetes Association (7-13-JF-61, 1-17-PDF-138 and 1-15-BS-184).

JOURNAL

Nature Neuroscience

DOI

10.1038/s41593-022-01062-0

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

A D2 to D1 shift in dopaminergic inputs to midbrain 5-HT neurons causes anorexia in mice

ARTICLE PUBLICATION DATE

2-May-2022

UTA biologist: Do chunky monkeys woo more mates?

Biologist investigates causes of seasonal weight gain in male squirrel monkeys

Grant and Award Announcement

UNIVERSITY OF TEXAS AT ARLINGTON

An evolutionary biologist at The University of Texas at Arlington is studying seasonal weight gain in male squirrel monkeys to determine its relationship to the species’ potential to sire offspring.

The National Science Foundation has awarded JC Buckner, assistant professor of biology, a four-year grant to study the Brazilian primates’ genetic traits and how they impact sexual selection.

During their brief mating season, male squirrel monkeys gain weight. Researchers think it is likely that the individuals who add the most pounds have the most reproductive success. That may occur because female squirrel monkeys find them more attractive than their thinner competitors.

Through DNA analysis, Buckner will investigate if weight gain is a sign of genetic quality to females who may be seeking a healthy mate. If packing on the pounds correlates with reproductive success and healthy genes, Buckner said it is likely that females are actively selecting the best parent for their offspring.

Simultaneously, her lab will look for alternate causes of weight gain. She hypothesizes that additional mass may help hopeful fathers challenge competing males and gain access to females. If this is true, then females would be viewed as playing a more passive role in mate selection.

At a time when biodiversity is in decline worldwide, basic biological research is necessary to further scientists’ understanding of species adaptability and survival, Buckner said.

“Humans and wildlife are increasingly affected by climate change and habitat degradation, which contribute to disease, novel stressors and population decline,” Buckner said. “Basic research like this is important to our understanding of the evolution of sexual signals and how they are used by species to adapt, reproduce and survive.”

Buckner’s investigation is funded by a collaborative grant awarded to UTA, California Lutheran University (CLU) and the University of California, Los Angeles (UCLA). Anita Stone, CLU assistant professor of biology, will spend four summers conducting field research in the eastern Amazonian forest. At UCLA, biological anthropologist Jessica Lynch will conduct paternity tests on biological samples from the baby monkeys that are born.

CAPTION

A Brazilian squirrel monkey rests on a tree branch.

CREDIT

Photo courtesy of Claire Meuter of Cal Lutheran

New report assesses global anti-deforestation measures

Comprehensive scientific report shows REDD+ progress and effects on climate, nature and people

Peer-Reviewed Publication

INTERNATIONAL UNION OF FOREST RESEARCH ORGANIZATIONS (IUFRO)

Reducing deforestation and forest degradation and their associated carbon emissions (REDD+) is part of the solution to climate change.
However, the role that REDD+ plays in reducing these emissions, while important, is limited given the magnitude of the problem and actions required in other greenhouse gas emitting sectors.
REDD+ implementation has the potential to deliver a range of benefits beyond reducing carbon if environmental and social aspects receive adequate attention.
The performance of REDD+ could be improved considerably by reducing the complexity of its governance and leveraging synergies with similar global initiatives.

(Vienna, 4 May 2022) A major scientific assessment on REDD+ is published today, evaluating the world’s progress towards goals to reduce emissions from deforestation and forest degradation. The report and policy brief, prepared by the Global Forest Expert Panels (GFEP) Programme led by the International Union of Forest Research Organizations (IUFRO), analyses the past 10 years of REDD+ implementation with respect to forest governance, carbon measurements and effects on biodiversity and livelihoods. The findings are presented in a webinar during the World Forestry Congress week.

One major conclusion is that while REDD+ has provided a convenient umbrella for many forest and land use related activities aimed at reducing deforestation and forest degradation – and associated greenhouse gas emissions – the interlinkages and complexities of relationships between forests, land use and climate are profound.

The report, which aims to inform ongoing policy discussions on the 2030 Agenda for Sustainable Development, comes at a pivotal time: Human-induced climate change and increases in extreme weather events are impacting nature and people faster and more severely than had been expected 20 years ago. However, there is still a chance to reverse this trend and avoid further global warming, according to the Intergovernmental Panel on Climate Change. This requires drastic reductions in greenhouse gas emissions, particularly CO2, most of which stem from burning fossil fuels. Forests also play an important role in the global carbon cycle: they absorb carbon as they grow and emit carbon when they are destroyed. Every year nearly one-third of the global carbon emissions produced by humans can be absorbed by forests, yet deforestation and forest degradation are responsible for up to 10% of the annual man-made CO2 emissions.

In addition, interest in forests as a ‘nature-based solution’ has probably never been higher and the number of initiatives aimed at conserving, sustainably managing and restoring forests has increased considerably.

“For example, there has been growing interest in forest landscape restoration (FLR) since the launch of the Bonn Challenge in 2011. This and other initiatives contribute to REDD+ but also overlap with it and often create confusion among stakeholders. Optimizing synergies with them and with other sectors is both a challenge and an opportunity,” says IUFRO Task Force Deputy Coordinator and environmental consultant Stephanie Mansourian, one of the lead authors.

In addition to promoting forest protection and carbon sink enhancement, a key focus of REDD+ is to move the scope of interventions beyond climate impacts towards an integrated view of climate, biodiversity and livelihoods. REDD+ can deliver numerous environmental benefits, including reduced soil erosion, enhanced water quality and quantity, and increased resilience to drought and floods. It can potentially deliver important biodiversity benefits, although the availability of up-to-date biodiversity data remains a major challenge. “Such benefits have significant economic importance and may increase both the value of REDD+ programs and people’s willingness to engage with them. However, in the implementation of REDD+, greater attention to biodiversity and livelihood outcomes is needed,” says lead author and IUFRO President John Parrotta of the USDA Forest Service.

Evidence from social evaluations of REDD+ interventions indicates that, where direct and indirect benefits are clearly visible to local stakeholders, and have been delivered, community engagement is strong and projects have achieved positive carbon and social outcomes, at least in the short term. Furthermore, explicit attention to rights and tenure issues provides more transparent mechanisms for the reporting and monitoring of environmental and social co-benefits, as well as better, more equitable outcomes, particularly for more vulnerable communities. Case studies from Indonesia show that insecure tenure can exacerbate distrust between resource users and the government, and can keep local people from further participating in REDD+ activities. Evidence from Latin America and the Caribbean suggests that deforestation is lower in areas where Indigenous and Tribal Peoples’ collective land rights are recognized.

“Since 2012, implementation of REDD+ has advanced considerably in many countries but ultimately it is REDD+ governance that determines its performance. Yet, governance is distributed across a complex landscape of institutions with different sources of authority and power dynamics that influence its outcomes,” says GFEP Programme Coordinator Christoph Wildburger.

REDD+ is being applied in a wide diversity of contexts with an equally wide diversity of governance strategies, which are changing over time. Brazil, for example, was initially a leading global source of deforestation, then a world leader in reducing deforestation, and is now experiencing rising deforestation once again. While Brazil’s federal government has played a key role in these swings in deforestation rates, a number of Brazilian states are pursuing their own REDD+ initiatives with positive outcomes. Ghana, a relatively small country where deforestation has been strongly linked to the production of cocoa for export, is pursuing the ‘world’s first commodity-driven’ REDD+ strategy with private sector investments in ‘climate smart cocoa’. Both Brazil and Ghana illustrate the important role that actors other than national governments may play in shaping REDD+, such as sub-national state actors or private companies trading in forest risk commodities like cocoa.

Report and policy brief: Download link

Fact sheet: Download link

Online study launch: Webinar

The International Union of Forest Research Organizations IUFRO is a world-wide organization devoted to forest research and related sciences. Its members are research institutions, universities, and individual scientists as well as decision-making authorities and other stakeholders with a focus on forests and trees.

The IUFRO-led Global Forest Expert Panels GFEP Programme provides policymakers with a stronger scientific basis for their decisions and policies related to the contributions of forests to mitigate and adapt to climate change.

For more information, please contact: Gerda Wolfrum at +43-1-8770151-17 or wolfrum(at)iufro.org

Background: REDD+ is a global action plan to reduce emissions from deforestation and forest degradation primarily in tropical and sub-tropical regions, where the largest forest losses take place.

Initially created as “REDD” by the United Nations Framework Convention on Climate Change in 2007, the “+” was added in 2010 to include conservation and enhancement of forest carbon stocks, and sustainable management of forests.

REDD+ was conceived as a framework for high-income countries to pay low- and middle-income countries for the conservation, sustainable management, and restoration of their forests. This happens, for example, through bilateral commitments such as those between Norway or Germany (currently the largest contributors), and Brazil or Indonesia as major recipients.

Although experience to date from over 65 countries provides useful insights into both challenges and lessons for the future of REDD+, determining the actual effects of REDD+ on forests, biodiversity and people is hampered by insufficient or inadequate measurement and reporting.

METHOD OF RESEARCH

Meta-analysis

ELECTROCHEMISTRY

A better way to create compounds for pharmaceuticals, other chemicals

Study uses new process to make complex molecules

Peer-Reviewed Publication

OHIO STATE UNIVERSITY

COLUMBUS, Ohio – What do gunpowder, penicillin and Teflon all have in common? They were inventions that took the world by storm, but they were all created by complete accident.

In a new study published in the journal Science, researchers used electricity to develop a tool that may make it easier and cheaper to fabricate the compounds used in pharmaceuticals and other natural products. Yet this invention, too, joins the ranks of the many unanticipated innovations that came before it.

Christo Sevov, co-author of the study and an assistant professor of chemistry and biochemistry at The Ohio State University, was part of a team that initially sought to prepare a catalyst that could be activated by electricity to make the bonds of the targeted drug compounds.

Their study’s findings suggest a general guideline for taking inexpensive and widely abundant materials, and using them to create complex compounds that wouldn’t normally work together. Streamlining this chemical process could allow researchers to safely create more valuable products with fewer steps and less waste.

But to actually facilitate their chemical reactions in the lab, instead of using high-energy reagents, or added substances, as is customary when synthesizing materials, Sevov’s team utilized the power of electricity.

Because electricity is ecologically sustainable, there’s recently been a push in the industrial sector to move toward the use of electrochemistry to foster chemical change.

“It's a very attractive way to do chemistry these days, because we have total control over how we run these reactions,” Sevov said.

The research has broad applications in medicine, and in the creation of products like agrichemicals (like pesticides or herbicides) and certain plastics. But Sevov’s discovery, while seemingly serendipitous, took lots of hard work and patience to get right.

“It took maybe three months of testing different combinations of additives, until all of a sudden something worked and it worked phenomenally well,” Sevov said. “Getting to that complex allowed us to stitch together materials that are very difficult to stitch together under normal circumstances.”

Because the precious metals many chemists use as catalysts can cost a pretty penny, Sevov’s team chose a nickel atom as the catalyst for their tool. In chemistry, catalysts are responsible for increasing or decreasing the rate of the chemical reaction as they make and create bonds.

“Being able to use catalysts that are very inexpensive, like nickel, is very beneficial to everyone in the entire community in general,” he said. Besides being a cheap alternative for businesses that produce pharmaceuticals, plastics and polymers, using nickel also keeps the cost of food products down. For example, if farmers had to pay more for the agrichemicals these chemical reactions help create, the price of their crop would rise proportionally, Sevov said.

To build on their research further, the team will go on to collaborate with Merck, a multinational pharmaceutical company, to try creating other products using more difficult reactions and more complex molecules. But with their latest discovery, Sevov said that he’s optimistic that their work will start to create brand new avenues in the field of chemistry.

“We’re going to take advantage of this really reactive intermediate and see how far we can run with it,” Sevov said.

Co-authors include Taylor Hamby and Matthew Lalama of Ohio State. This research was supported by the National Institutes of Health.

Written By Tatyana Woodall, Woodall.52@osu.edu