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New imaging technique allows researchers to see gene expression in brains of live mice in real time

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A University of Minnesota Twin Cities-led team has developed a new technique that allows scientists and engineers to, for the first time, visualize mRNA molecules in the brains of living mice. The research reveals new insights into how memories are formed and stored in the brain and could provide scientists with new information about diseases such as Alzheimer’s.

The paper is published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), a peer-reviewed, multidisciplinary, high-impact scientific journal.

There is still a lot of mystery surrounding the process of how memory is physically created and stored in the brain. It is well known that mRNA—a type of RNA involved in the creation of proteins—is produced during the process of forming and storing memories, but the technology for studying this process on the cellular level has been limited. Previous studies have often involved dissecting mice in order to examine their brains.

A team of researchers led by a University of Minnesota Twin Cities faculty member has developed a new technique that gives scientists a window into RNA synthesis in the brain of a mouse while it is still alive.

“We still know very little about memories in the brain,” explained Hye Yoon Park, an associate professor in the University of Minnesota Department of Electrical and Computer Engineering and the study’s lead author. “It’s well known that mRNA synthesis is important for memory, but it was never possible to image this in a live brain. Our work is an important contribution to this field. We now have this new technology that neurobiologists can use for various different experiments and memory tests in the future.”

The University of Minnesota-led team’s process involved genetic engineering, two-photon excitation microscopy, and optimized image processing software. By genetically modifying a mouse so that it produced mRNA labeled with green fluorescent proteins (proteins derived from a jellyfish), the researchers were able to see when and where the mouse’s brain generated Arc mRNA, the specific type of molecule they were looking for.

Because the mouse is alive, the researchers could study it for longer periods of time. Using this new process, the researchers performed two experiments on the mouse in which they were able to see in real time over a month what the neurons—or nerve cells—were doing as the mouse was forming and storing memories.

Historically, neuroscientists have theorized that certain groups of neurons in the brain fire when a memory is formed, and that those same cells fire again when that moment or event is remembered. However, in both experiments, the researchers found that different groups of neurons fired each day they triggered the memory in the mouse.

Over the course of several days after the mouse created this memory, they were able to locate a small group of cells that overlapped, or consistently generated the Arc mRNA each day, in the retrosplenial cortex (RSC) region of the brain, a group which they believe is responsible for the long-term storage of that memory.

“Our research is about memory generation and retrieval,” Park said. “If we can understand how this happens, it will be very helpful for us in understanding Alzheimer’s disease and other memory-related diseases. Maybe people with Alzheimer’s disease still store the memories somewhere—they just can’t retrieve them. So in the very long-term, perhaps this research can help us overcome these diseases.”

This research was funded by the Samsung Science and Technology Foundation and the Wellcome Trust.

In addition to Park, the team included Seoul National University researchers Byung Hun Lee, Jae Youn Shim, Hyungseok Moon, and Dong Wook Kim; and Korea Institute of Science and Technology researchers Jiwon Kim, Jang Soo Yook, and Jinhyun Kim.

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Mindfulness meditation reduces pain by separating it from the self

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For centuries, people have been using mindfulness meditation to try to relieve their pain, but neuroscientists have only recently been able to test if and how this actually works. In the latest of these efforts, researchers at University of California San Diego School of Medicine measured the effects of mindfulness on pain perception and brain activity.

The study, published July 7, 2022 in PAIN, showed that mindfulness meditation interrupted the communication between brain areas involved in pain sensation and those that produce the sense of self. In the proposed mechanism, pain signals still move from the body to the brain, but the individual does not feel as much ownership over those pain sensations, so their pain and suffering are reduced.

“One of the central tenets of mindfulness is the principle that you are not your experiences,” said senior author Fadel Zeidan, PhD, associate professor of anesthesiology at UC San Diego School of Medicine. “You train yourself to experience thoughts and sensations without attaching your ego or sense of self to them, and we’re now finally seeing how this plays out in the brain during the experience of acute pain.”

On the first day of the study, 40 participants had their brains scanned while painful heat was applied to their leg. After experiencing a series of these heat stimuli, participants had to rate their average pain levels during the experiment.

Participants were then split into two groups. Members of the mindfulness group completed four separate 20-minute mindfulness training sessions. During these visits, they were instructed to focus on their breath and reduce self-referential processing by first acknowledging their thoughts, sensations and emotions but then letting them go without judging or reacting to them. Members of the control group spent their four sessions listening to an audio book.

On the final day of the study, both groups had their brain activity measured again, but participants in the mindfulness group were now instructed to meditate during the painful heat, while the control group rested with their eyes closed.

Researchers found that participants who were actively meditating reported a 32 percent reduction in pain intensity and a 33 percent reduction in pain unpleasantness.

“We were really excited to confirm that you don’t have to be an expert meditator to experience these analgesic effects,” said Zeidan. “This is a really important finding for the millions of people looking for a fast-acting and non-pharmacological treatment for pain.”

When the team analyzed participants’ brain activity during the task, they found that mindfulness-induced pain relief was associated with reduced synchronization between the thalamus (a brain area that relays incoming sensory information to the rest of the brain) and parts of the default mode network (a collection of brain areas most active while a person is mind-wandering or processing their own thoughts and feelings as opposed to the outside world).

One of these default mode regions is the precuneus, a brain area involved in fundamental features of self-awareness, and one of the first regions to go offline when a person loses consciousness. Another is the ventromedial prefrontal cortex, which includes several sub regions that work together to process how you relate to or place value on your experiences. The more these areas were decoupled or deactivated, the more pain relief the participant reported.

“For many people struggling with chronic pain, what often affects their quality of life most is not the pain itself, but the mental suffering and frustration that comes along with it,” said Zeidan. “Their pain becomes a part of who they are as individuals — something they can’t escape — and this exacerbates their suffering.”

By relinquishing the self-referential appraisal of pain, mindfulness meditation may provide a new method for pain treatment. Mindfulness meditation is also free and can be practiced anywhere. Still, Zeidan said he hopes trainings can be made even more accessible and integrated into standard outpatient procedures.

“We feel like we are on the verge of discovering a novel non-opioid-based pain mechanism in which the default mode network plays a critical role in producing analgesia. We are excited to continue exploring the neurobiology of mindfulness and its clinical potential across various disorders.”

Co-authors include: Gabriel Riegner, Valeria Oliva and William Mobley at UC San Diego, as well as Grace Posey at Tulane University and Youngkyoo Jung at University of California Davis.

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Only seven percent of adults have good cardiometabolic health

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Less than 7 percent of the U.S. adult population has good cardiometabolic health, a devastating health crisis requiring urgent action, according to research led by a team from the Friedman School of Nutrition Science and Policy at Tufts University in a pioneering perspective on cardiometabolic health trends and disparities published in the July 12 issue of the Journal of the American College of Cardiology. Their team also included researchers from Tufts Medical Center.

Researchers evaluated Americans across five components of health: levels of blood pressure, blood sugar, blood cholesterol, adiposity (overweight and obesity), and presence or absence of cardiovascular disease (heart attack, stroke, etc.). They found that only 6.8 percent of U.S. adults had optimal levels of all five components as of 2017-2018. Among these five components, trends between 1999 and 2018 also worsened significantly for adiposity and blood glucose. In 1999, 1 out of 3 adults had optimal levels for adiposity (no overweight or obesity); that number decreased to 1 out of 4 by 2018. Likewise, while 3 out of 5 adults didn’t have diabetes or prediabetes in 1999, fewer than 4 out of 10 adults were free of these conditions in 2018.

“These numbers are striking. It’s deeply problematic that in the United States, one of the wealthiest nations in the world, fewer than 1 in 15 adults have optimal cardiometabolic health,” said Meghan O’Hearn, a doctoral candidate at the Friedman School and the study’s lead author. “We need a complete overhaul of our healthcare system, food system, and built environment, because this is a crisis for everyone, not just one segment of the population.”

The study looked at a nationally representative sample of about 55,000 people aged 20 years or older from 1999 to 2018 from the 10 most recent cycles of the National Health and Nutrition Examination Survey. The research team focused on optimal, intermediate, and poor levels of cardiometabolic health and its components, rather than just presence or absence of disease. “We need to shift the conversation, because disease is not the only problem,” O’Hearn said. “We don’t just want to be free of disease. We want to achieve optimal health and well-being.”

The researchers also identified large health disparities between people of different sexes, ages, races and ethnicities, and education levels. For example, adults with less education were half as likely to have optimal cardiometabolic health compared with adults with more education, and Mexican Americans had one-third the optimal levels versus non-Hispanic White adults. Additionally, between 1999 and 2018, while the percentage of adults with good cardiometabolic health modestly increased among non-Hispanic White Americans, it went down for Mexican American, other Hispanic, non-Hispanic Black, and adults of other races.

“This is really problematic. Social determinants of health such as food and nutrition security, social and community context, economic stability, and structural racism put individuals of different education levels, races, and ethnicities at an increased risk of health issues,” said Dariush Mozaffarian, dean of the Friedman School and senior author. “This highlights the other important work going on across the Friedman School and Tufts University to better understand and address the underlying causes of poor nutrition and health disparities in the U.S. and around the world.”

The study also assessed “intermediate” levels of health—not optimal but not yet poor—including conditions like pre-diabetes, pre-hypertension, and overweight. “A large portion of the population is at a critical inflection point,” O’Hearn said. “Identifying these individuals and addressing their health conditions and lifestyle early is critical to reducing growing healthcare burdens and health inequities.”

The consequences of the dire state of health among U.S. adults reach beyond personal health. “Its impacts on national healthcare spending and the financial health of the entire economy are enormous,” O’Hearn said. “And these conditions are largely preventable. We have the public health and clinical interventions and policies to be able to address these problems.”

Researchers at the Friedman School work actively on many such solutions, O’Hearn said, including Food is Medicine interventions (using good nutrition to help prevent and treat illness); incentives and subsidies to make healthy food more affordable; consumer education on a healthy diet; and private sector engagement to drive a healthier and more equitable food system. “There are a lot of different avenues through which this can be done,” O’Hearn said. “We need a multi-sectoral approach, and we need the political will and desire to do it.”

“This is a health crisis we’ve been facing for a while,” O’Hearn said. “Now there’s a growing economic, social and ethical imperative to give this problem significantly more attention than it has been getting.”

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Máxima talks to students about mental health

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Queen Máxima studied the mental health of students in higher and scientific education at Leiden University of Applied Sciences on Wednesday. She paid a working visit to the institution, where she spoke with students, among others, who have developed initiatives to improve their well-being.

The Queen is honorary president of MIND Us, a foundation that strives to help young people get a grip on their mental health, develop resiliently and find help when needed.

Students from Fresh Thoughts, for example, told her on Wednesday in Leiden about their Walk and Talks in which young people discuss mental challenges they experience.

Many students deal with stress, loneliness and pressure to perform. That is why five Leiden parties have recently signed the Student Welfare Declaration “after alarming reports”: the Municipality of Leiden, Leiden University, Leiden University of Applied Sciences, the Local Chamber of Associations and the Study Association Consultation Platform. Máxima also spoke with the initiators of the statement, which should also lead to an action plan.

According to one of the students, depression, increasing drug use and being really unhappy are noticeable in groups of friends, especially in times of corona. While, according to him, it seemed in the media during the corona crisis that students were not behaving responsibly. Students in their student city often do not have a GP either, which means that it takes a long time before they are treated and the problems become even worse.

Although it is not always self-evident to pay attention to these problems, a lot is already being given to guidance, by coaches and psychologists, who, according to one of the students, make it clear that it is not so bad to experience a study delay once in a while. Daniël Wigboldus, rector of Radboud University, talked about a project called “messwork”. People shared their own failures, including teachers. When he once did that in the lecture hall, he saw “a sigh of relief pass through the hall”.

But failure is difficult, the pressure to perform and social pressure are very high. “I think it’s best for a stressed generation,” said a representative of InHolland. A major problem is that the people who most need the many initiatives are the most difficult to reach, it was said. The Queen thinks it is necessary to do more research into performance pressure.

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