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Chronic opioid treatment may raise risk of post-traumatic stress disorder, study finds

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Senior author Michael Fanselow said the research suggests that chronic opioid use increases susceptibility to developing anxiety disorders. Photo credit: Reed Hutchinson/UCLA

While opioids are often prescribed to treat people with trauma-related pain, a new UCLA-led study suggests doctors should use caution before prescribing the drug to those they believe may experience severe stress in the future, in order to reduce the risk the patient will develop PTSD.

In the study, researchers administered doses of the opioid morphine to a group of 22 mice for one week, then gave the mice relatively strong foot shocks. After the morphine wore off, the mice were given mild electric foot shocks. These mice showed a substantially longer “freezing response” than a second, control group of 24 mice that had not been given morphine. When mice recall a frightening memory, they freeze. Their heart rates and blood pressure go up, and the more frightening the memory, the more they freeze.

“While we are generally aware that drug use, such as that in the current opioid crisis, has many deleterious effects, our results suggest yet another effect — increased susceptibility to developing anxiety disorders,” said senior author Michael Fanselow, UCLA distinguished Staglin family professor of psychology and director of UCLA’s Staglin Family Music Festival Center for Brain and Behavioral Health. “As opioids are often prescribed to treat symptoms such as pain that may accompany trauma, caution may be needed because this may lead to a greater risk of developing PTSD, if exposed to further traumatic events, such as an accident, later on.”

“The foot shocks produced lasting fear and anxiety-like behaviors, such as freezing,” Fanselow said.

“Our data are the first to show a possible effect of opioids on future fear learning, suggesting that a person with a history of opioid use may become more susceptible to the negative effects of stress,” Fanselow said. “The ability of opioids to increase PTSD-like symptoms far outlasted the direct effects of the drug or withdrawal from the drug, suggesting the effect may continue even after opioid treatment has stopped.”

Fanselow’s view is if there is reason to believe a patient is likely to experience severe emotional stress after opioid treatment, then doctors should use caution about prescribing an opioid. If opioid use is medically called for, then the patient should be kept away from potentially stressful situations. So, for example, a soldier treated with opioids for pain should not be sent back into combat for a period of time, he said. The development of post-traumatic stress disorder requires some stressful experience after opioid use, he said.

The researchers also gave some of the mice morphine after the initial trauma had occurred but before exposing them to the second, mild stressor. They found that mice treated with morphine after the initial trauma did not show enhanced fear learning following exposure to the mild stressor. This finding suggests that chronic use of opioids before — but not after — a traumatic event occurs affects fear learning during subsequent stressful events.

The researchers concluded the mice given morphine were more susceptible to post-traumatic stress disorder than the control group of mice not given any opioids, and inferred that people with a history of using opioids are more susceptible to PTSD than the general population.

The study is published in Neuropsychopharmacology, an international scientific journal focusing on clinical and basic science research that advances understanding of the brain and behavior.

The research was funded by the National Institute on Drug Abuse and National Institute of Mental Health.

An opiate is a drug naturally derived from the opium poppy plant, such as heroin, morphine and codeine. Opioid is a broader term that includes opiates and any substance, natural or synthetic, that binds to the brain’s opioid receptors — which play a key role in controlling pain, rewards and addictive behaviors. Synthetic opioids include the prescription painkillers Vicodin and OxyContin, as well as fentanyl and methadone.

Substance abuse and PTSD often go hand-in-hand, Fanselow said, and people with PTSD often take drugs to self-medicate. Nearly 40% of people with PTSD also have a drug disorder.

Fanselow and colleagues reported last month that a traumatic brain injury causes changes in a brain region called the amygdala; and the brain processes fear differently after such an injury.

This article originally appeared in the UCLA Newsroom.

Student Spotlight – Julia Nakamura

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Photo of student smiling.

Fourth-year UCLA student researcher Julia Nakamura

Meet fourth-year UCLA student researcher Julia Nakamura!

Julia majors in Psychobiology with a minor in Gerontology and is in our Undergraduate Research Scholars Program. The title of her research project is “The Role of Social Support in the Association between Early Life Stress, Depression, and Inflammation in Older Adults.”

 

How did you first get interested in your research project?

UCLA’s Cluster course “Frontiers in Human Aging” initially sparked my interest in aging populations. Through a service learning project at ONEgeneration Adult Day Care Center, I directly witnessed the burden of chronic disease in later-life adults and realized the pressing need to understand the mechanisms underlying these adverse health outcomes. Through my coursework in psychology, I became interested in the psychological factors that influence biological mechanisms and have the potential to positively impact the trajectory of chronic disease outcomes.

I began research in psychology in Dr. Julienne Bower’s Mind-Body Lab under the direction of Dr. Kate Kuhlman. We study the effects of childhood adversity on biological and behavioral responses to psychological stress. My experiences in this lab led me to wonder what factors could mitigate adverse physical and mental health outcomes from stressful experiences, specifically in older adults. My honors research projects examines if social support moderates the relationship between early-life stress, depressive symptoms, and inflammation in older adults using data from the Health and Retirement Study.

What has been the most exciting aspect of your research so far?

Getting to test my own research questions has been the best part of this project. Specifically, it has been really exciting for me to run my own data analyses for the first time with Dr. Kuhlman’s guidance. Experiencing the “behind-the-scenes” of research and systematically moving through the steps of conducting an independent project has been really informative. This project has helped me to feel that I am truly developing the skill set of an independent researcher, which is very exciting!

What has surprised you about your research or the research process?

The immensely collaborative nature of research in academia was quite surprising to me when I first started on this project. Through my research, I’ve had the privilege of working with several scientists and professors who are experts in their respective areas of study. They have all welcomed me and helped to make my project as scientifically sound and comprehensive as possible. Research really builds on itself. Learning from other people’s projects and ideas, even if they are outside of your immediate area of study, can result in high levels of collaboration and really interesting research!

What is one piece of advice you have for other UCLA students thinking about doing research?

I would advise students interested in research to actively pursue research opportunities. There are plenty of amazing opportunities to be involved in research at UCLA, but you have to seek them out. It can be intimidating to take the initial steps to reach out to professors and discuss their research interests, but it is so worthwhile to find a lab and professor that are a good fit! I would recommend that students find an area of study that they are really passionate about. I think that your passion for your area of study and your continued curiosity will drive your research questions and help you get the most out of each research experience.

What effect do you hope your research has in your field, at UCLA, in your community, or in the world?

I hope to spend my life contributing to our understanding of the biobehavioral processes that promote mental and physical health across the lifespan. As the number of older adults (a majority of whom have at least one chronic disease) increase in our society, it is now more important than ever to identify potential intervention targets that can improve the trajectory of chronic disease outcomes.

This article originally appeared on the Undergraduate Research Center website.

One of California’s iconic tree species offers lessons for conservation

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Picture of a valley oak tree.

The valley oak, the largest oak in California, grows to over 100 feet tall and provides habitat and food for a variety of animals. Photo credit: Victoria Sork/UCLA

 

With increasing regularity, Californians are witnessing firsthand the destructive power of wildfires. But not everyone sees what happens after the flames die down, when debris is cleared, homes and lives rebuilt — and trees replanted to help nature recover.

New research led by UCLA evolutionary biologist Victoria Sork examines whether the trees being replanted in the wake of California’s fires will be able to survive a climate that is continuing to warm.

The study, which is published in the Proceedings of the Natural Academy of Sciences, focuses on California’s iconic valley oak. The research is among the first to demonstrate the potential of using genomics to inform conservation strategies — essentially giving species an evolutionary boost. The study showed that planting trees that are genetically better suited to higher temperatures makes them more likely to survive and grow to maturity.

“When we think about managing ecosystems under rapidly changing climates, we have to realize trees need to be able to survive past 50 years,” Sork said.

The paper also discovered something surprising: The valley oak, an essential component of many ecosystems in California, is already poorly adapted to its environment — even considering climate conditions in 2019.

“They actually seem to grow better in cooler climates than they’re in right now,” said Luke Browne, a postdoctoral scholar at the UCLA La Kretz Center for California Conservation Science and the study’s lead author. “They might grow better if climates were more like they were 21,000 years ago, during the last ice age.”

During the peak of the last ice age, summer temperatures were about 4 to 5 degrees Celsius colder, and ice covered most of Canada and mountainous areas of the U.S.

In the fields of conservation and land management, it is a common assumption that plants and animals are adapted to their environments — that’s how evolution and natural selection are supposed to work. The new research casts doubt on that assumption.

The study is part of an ongoing project initiated by Sork and Jessica Wright, an expert in conservation genetics at the USDA Forest Service, more than 10 years ago.

Researchers gathered 11,000 seeds from 94 locations throughout the trees’ range, which stretches from the Santa Monica Mountains to the Cascade foothills in the northern part of the state. They grew them to saplings in a greenhouse and planted them in two large experimental gardens, in Chico and Placerville, California. They tracked how well trees from different locations grew, and sequenced the genomes of their mother trees to link genetic information and growth rates.

The researchers then identified which genetic variants would be more likely to thrive as climate change continues to warm California. They predicted that, under predicted future warmer temperatures, trees containing beneficial genetic variations would have 11% higher growth rates than the average for all of the trees in the experiment, and 25% higher growth rates than the trees without the beneficial variations.

Information like that could help the U.S. Forest Service, for example, in its efforts to restore forests with species that have the best chance for long-term survival.

“Studies like this one provide valuable insights that help land managers make informed decisions on reforestation projects,” Wright said. “When planting trees in a particular location, managers have to decide where to collect the acorns.”

By 2070, average temperatures in the state are projected to be up to 4.8 degrees warmer than they were during the mid- to late 20th century.

“That’s going to have consequences for how fast these trees grow,” Browne said. “We’re at a challenging time to figure out the best way to do conservation science. This paper shows one approach we could use that takes advantage of modern genomics.”

The study did not determine why valley oaks are not well adapted to their environment. It might be because the climate has already warmed up so much, the trees’ long lifespans — up to 500 years — or some other, unknown factor.

The valley oak is the largest oak in California; it grows to over 100 feet tall, and has dark green leaves and a deeply grooved trunk. It is considered a foundational species because it provides habitat and food for a variety of animals, including squirrels, birds, deer and insects. In parts of the state, it is one of the only species of tree that exists. Valley oaks provide benefits to humans, too: filtering water and providing shady places to escape the heat.

Although it focuses on the oak, the paper has broader implications for conservation science in a changing climate — especially for species that evolve and adapt slowly. That’s what Sork and Wright were thinking when they initiated the project.

At the time, they hoped to find conservation strategies that could eventually be implemented using genetic information alone — without extensive field experiments.

“Not everyone in the world is going to be able to collect 11,000 seeds and plant them in a common garden,” Sork said.

This article originally appeared in the UCLA Newsroom.

What wolves’ teeth reveal about their lives

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Biologist Blaire Van Valkenburgh has spent more than three decades studying the skulls of large carnivores. Here she displays a replica of a saber-toothed cat skull. At left are the skulls of a spotted hyena (in white) and a dire wolf (the black skull). Photo credit: Christelle Snow/UCLA.

UCLA evolutionary biologist Blaire Van Valkenburgh has spent more than three decades studying the skulls of many species of large carnivores — including wolves, lions and tigers —  that lived from 50,000 years ago to the present. She reports today in the journal eLife the answer to a puzzling question.

Essential to the survival of these carnivores is their teeth, which are used for securing their prey and chewing it, yet large numbers of these animals have broken teeth. Why is that, and what can we learn from it?

In the research, Van Valkenburgh reports a strong link between an increase in broken teeth and a decline in the amount of available food, as large carnivores work harder to catch dwindling numbers of prey, and eat more of it, down to the bones.

“Broken teeth cannot heal, so most of the time, carnivores are not going to chew on bones and risk breaking their teeth unless they have to,” said Van Valkenburgh, a UCLA distinguished professor of ecology and evolutionary biology, who holds the Donald R. Dickey Chair in Vertebrate Biology.

For the new research, Van Valkenburgh studied the skulls of gray wolves — 160 skulls of adult wolves housed in the Yellowstone Heritage and Research Center in Montana; 64 adult wolf skulls from Isle Royale National Park in Lake Superior that are housed at Michigan Technological University; and 94 skulls from Scandinavia, collected between 1998 and 2010, housed in the Swedish Royal Museum of Natural History in Stockholm. She compared these with the skulls of 223 wolves that died between 1874 and 1952, from Alaska, Texas, New Mexico, Idaho and Canada.

Yellowstone had no wolves, Van Valkenburgh said, between the 1920s and 1995, when 31 gray wolves were brought to the national park from British Columbia. About 100 wolves have lived in Yellowstone for more than a decade, she said.

In Yellowstone, more than 90% of the wolves’ prey are elk. The ratio of elk to wolves has declined sharply, from more than 600-to-1 when wolves were brought back to the national park to about 100-to-1 more recently.

In the first 10 years after the reintroduction, the wolves did not break their teeth much and did not eat the elk completely, Van Valkenburgh reports. In the following 10 years, as the number of elk declined, the wolves ate more of the elk’s body, and the number of broken teeth doubled, including the larger teeth wolves use when hunting and chewing.

The pattern was similar in the island park of Isle Royale. There, the wolves’ prey are primarily adult moose, but moose numbers are low and their large size makes them difficult to capture and kill. Isle Royale wolves had high frequencies of broken and heavily worn teeth, reflecting the fact that they consumed about 90% of the bodies of the moose they killed.

Scandinavian wolves presented a different story. The ratio of moose to wolves is nearly 500-to-1 in Scandinavia and only 55-to-1 in Isle Royale, and, consistent with Van Valkenburgh’s hypothesis, Scandinavian wolves consumed less of the moose they killed (about 70%) than Isle Royale wolves. Van Valkenburgh did not find many broken teeth among the Scandinavian wolves. “The wolves could find moose easily, not eat the bones, and move on,” she said.

Van Valkenburgh believes her findings apply beyond gray wolves, which are well-studied, to other large carnivores, such as lions, tigers and bears.

Extremely high rates of broken teeth have been recorded for large carnivores — such as lions, dire wolves and saber-toothed cats — from the Pleistocene epoch, dating back tens of thousands of years, compared with their modern counterparts, Van Valkenburgh said. Rates of broken teeth from animals at the La Brea Tar Pits were two to four times higher than in modern animals, she and colleagues reported in the journal Science in the 1990s.

“Our new study suggests that the cause of this tooth fracture may have been more intense competition for food in the past than in present large carnivore communities,” Van Valkenburgh said.

She and colleagues reported in 2015 that violent attacks by packs of some of the world’s largest carnivores — including lions much larger than those of today and saber-toothed cats — went a long way toward shaping ecosystems during the Pleistocene.

In a 2016 article in the journal BioScience, Van Valkenburgh and more than 40 other wildlife experts wrote that preventing the extinction of lions, tigers, wolves, bears, elephants and the world’s other largest mammals will require bold political action and financial commitments from nations worldwide.

Discussing the new study, she said, “We want to understand the factors that increase mortality in large carnivores that, in many cases, are near extinction. Getting good information on that is difficult. Studying tooth fracture is one way to do so, and can reveal changing levels of food stress in big carnivores.”

Co-authors are Rolf Peterson and John Vucetich, professors of forest resources and environmental science at Michigan Technological University; and Douglas Smith and Daniel Stahler, wildlife biologists with the National Park Service.

The research was funded by the National Science Foundation and National Park Service.

This article originally appeared in the UCLA Newsroom.

Study shows how serotonin and a popular anti-depressant affect the gut’s microbiota

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Senior author Elaine Hsiao says researchers hope to build on their current study to learn whether microbial interactions with antidepressants have consequences for health and disease. Photo: Reed Hutchinson/UCLA

A new study in mice led by UCLA biologists strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota — the 100 trillion or so bacteria and other microbes that live in the human body’s intestines.

Serotonin — a neurotransmitter, or chemical messenger that sends messages among cells — serves many functions in the human body, including playing a role in emotions and happiness. An estimated 90% of the body’s serotonin is produced in the gut, where it influences gut immunity.

The team — led by senior author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow — identified a specific gut bacterium that can detect and transport serotonin into bacterial cells. When mice were given the antidepressant fluoxetine, or Prozac, the biologists found this reduced the transport of serotonin into their cells. This bacterium, about which little is known, is called Turicibacter sanguinis. The study is published this week in the journal Nature Microbiology.

“Our previous work showed that particular gut bacteria help the gut produce serotonin. In this study, we were interested in finding out why they might do so,” said Hsiao, UCLA assistant professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College; and of digestive diseases in the David Geffen School of Medicine at UCLA.

Hsiao and her research group reported in the journal Cell in 2015 that in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao’s team raised mice without the bacteria, more than 50% of their gut serotonin was missing. The researchers then added the bacteria mixture of mainly Turicibacter and Clostridia, and their serotonin increased to a normal level.

That study got the team wondering why bacteria signal to our gut cells to make serotonin. Do microbes use serotonin, and if so, for what?

In this new study, the researchers added serotonin to the drinking water of some mice and raised others with a mutation (created by altering a specific serotonin transporter gene) that increased the levels of serotonin in their guts. After studying the microbiota of the mice, the researchers discovered that the bacteria Turicibacter and Clostridia increased significantly when there was more serotonin in the gut.

If these bacteria increase in the presence of serotonin, perhaps they have some cellular machinery to detect serotonin, the researchers speculated. Together with study co-author Lucy Forrest and her team at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, the researchers found a protein in multiple species of Turicibacter that has some structural similarity to a protein that transports serotonin in mammals. When they grew Turicibacter sanguinis in the lab, they found that the bacterium imports serotonin into the cell.

In another experiment, the researchers added the antidepressant fluoxetine, which normally blocks the mammalian serotonin transporter, to a tube containing Turicibacter sanguinis. They found the bacterium transported significantly less serotonin.

The team found that exposing Turicibacter sanguinis to serotonin or fluoxetine influenced how well the bacterium could thrive in the gastrointestinal tract. In the presence of serotonin, the bacterium grew to high levels in mice, but when exposed to fluoxetine, the bacterium grew to only low levels in mice.

“Previous studies from our lab and others showed that specific bacteria promote serotonin levels in the gut,” Fung said. “Our new study tells us that certain gut bacteria can respond to serotonin and drugs that influence serotonin, like anti-depressants. This is a unique form of communication between bacteria and our own cells through molecules traditionally recognized as neurotransmitters.”

The team’s research on Turicibacter aligns with a growing number of studies reporting that anti-depressants can alter the gut microbiota. “For the future,” Hsiao said, “we want to learn whether microbial interactions with antidepressants have consequences for health and disease.” Hsiao wrote a blog post for the journal about the new research.

Other study co-authors are Helen Vuong, Geoffrey Pronovost, Cristopher Luna, Anastasia Vavilina, Julianne McGinn and Tomiko Rendon, all of UCLA; and Antoniya Aleksandrova and Noah Riley, members of Forrest’s team.

The research was supported by funding from the National Institutes of Health’s Director’s Early Independence Award, Klingenstein-Simons Fellowship Award, and David & Lucile Packard Foundation’s Packard Fellowship for Science and Engineering.

This article originally appeared in the UCLA Newsroom.

Minds Matter: Raising the Curtain on Depression and Anxiety

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Photo of Cleveland Cavaliers basketball player Kevin Love and UCLA College’s Clinical Psychology expert Michelle Craske.

Cleveland Cavaliers basketball player Kevin Love and UCLA College’s Clinical Psychology expert Michelle Craske.

UCLA students, community members and supporters joined Cleveland Cavaliers basketball player Kevin Love and UCLA College’s Clinical Psychology expert Michelle Craske for a standing-room only hybrid class and public lecture on Monday, August 19, for “Minds Matter: Raising the Curtain on Depression and Anxiety,” a free hour-long discussion on the causes of depression and anxiety, public stigma, and potential advances for the future. The series was the first in an ongoing exploration of brain health that will continue with additional events focusing on bullying, aging well, and other topics.

Love, an NBA Champion and five-time NBA All-Star for the Cleveland Cavaliers, has publicly discussed his struggle with panic attacks and anxiety and his decision to seek therapy, and has become a leading voice in mental health advocacy and founded the Kevin Love Fund in 2018 with the mission of inspiring people to live their healthiest lives while providing the tools to achieve physical and emotional well-being.

“Mental health isn’t just an athlete thing, it’s an issue that affects everyone in some way. The more we can normalize the conversation around mental health, the more we can do to help those that are struggling,” said Love. “My goal in sharing my personal experience is to connect with others who are going through something and keep this dialogue top of mind.”

Michelle G. Craske is a UCLA Professor of Psychology, Psychiatry and Biobehavioral Sciences, Director of the Anxiety and Depression Research Center, and Associate Director of the Staglin Family Music Center for Behavioral and Brain Health. Craske has published extensively in the area of fear, anxiety and depression.

“We need to work together to bring anxiety and depression out of the dark. People who suffer will only seek help when they can do so without fear of shame. Event series such as ‘Minds Matter’ aim to shed a light on these critical issues, and to help make a positive breakthrough,” said Craske.

Craske also is Director of the Innovative Treatment Network within the UCLA Depression Grand Challenge, a campus-wide effort to cut the global burden of depression in half. The innovative treatment component, which Craske leads, seeks to develop novel and more effective treatments for depression and anxiety and increase the scalability and accessibility of existing evidence-based treatments.

The “Minds Matter” series leverages the strengths of UCLA College’s Psychology faculty as well as high-profile guests who provide specialized insight about the discussion topic. Upcoming sessions will include discussions on addiction, adolescent brain development and behavior, bullying, healthy aging, and thriving under stress. The “Minds Matter” series is made possible through the longstanding UCLA College and Geffen Playhouse partnership and the generous support of donors.

Check back for information on future “Minds Matter” events at  https://www.college.ucla.edu/seniorsurvey/minds-matter/.

Biochemists discover new insights into what may go awry in brains of people with Alzheimer’s

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Photo of two researchers in lab.

Research by UCLA professor Steven Clarke and former graduate student Rebeccah Warmack, as well as UCLA colleagues, reveals new information about the brain’s biochemistry.

More than three decades of research on Alzheimer’s disease have not produced any major treatment advances for those with the disorder, according to a UCLA expert who has studied the biochemistry of the brain and Alzheimer’s for nearly 30 years. “Nothing has worked,” said Steven Clarke, a distinguished professor of chemistry and biochemistry. “We’re ready for new ideas.” Now, Clarke and UCLA colleagues have reported new insights that may lead to progress in fighting the devastating disease.

Scientists have known for years that amyloid fibrils — harmful, elongated, water-tight rope-like structures — form in the brains of people with Alzheimer’s, and likely hold important clues to the disease. UCLA Professor David Eisenberg and an international team of chemists and molecular biologists reported in the journal Nature in 2005 that amyloid fibrils contain proteins that interlock like the teeth of a zipper. The researchers also reported their hypothesis that this dry molecular zipper is in the fibrils that form in Alzheimer’s disease, as well as in Parkinson’s disease and two dozen other degenerative diseases. Their hypothesis has been supported by recent studies.

Alzheimer’s disease, the most common cause of dementia among older adults, is an irreversible, progressive brain disorder that kills brain cells, gradually destroys memory and eventually affects thinking, behavior and the ability to carry out the daily tasks of life. More than 5.5 million Americans, most of whom are over 65, are thought to have dementia caused by Alzheimer’s.

The UCLA team reports in the journal Nature Communications that the small protein beta amyloid, also known as a peptide, that plays an important role in Alzheimer’s has a normal version that may be less harmful than previously thought and an age-damaged version that is more harmful.

Rebeccah Warmack, who was a UCLA graduate student at the time of the study and is its lead author, discovered that a specific version of age-modified beta amyloid contains a second molecular zipper not previously known to exist. Proteins live in water, but all the water gets pushed out as the fibril is sealed and zipped up. Warmack worked closely with UCLA graduate students David Boyer, Chih-Te Zee and Logan Richards; as well as senior research scientists Michael Sawaya and Duilio Cascio.

What goes wrong with beta amyloid, whose most common forms have 40 or 42 amino acids that are connected like a string of beads on a necklace?

The researchers report that with age, the 23rd amino acid can spontaneously form a kink, similar to one in a garden hose. This kinked form is known as isoAsp23. The normal version does not create the stronger second molecular zipper, but the kinked form does.

“Now we know a second water-free zipper can form, and is extremely difficult to pry apart,” Warmack said. “We don’t know how to break the zipper.”

The normal form of beta amyloid has six water molecules that prevent the formation of a tight zipper, but the kink ejects these water molecules, allowing the zipper to form.

When one of its amino acids forms a kink, beta amyloid creates a harmful molecular zipper, shown here in green. Photo credit: Rebeccah Warmack/UCLA

When one of its amino acids forms a kink, beta amyloid creates a harmful molecular zipper, shown here in green.
“Rebeccah has shown this kink leads to faster growth of the fibrils that have been linked to Alzheimer’s disease,” said Clarke, who has conducted research on biochemistry of the brain and Alzheimer’s disease since 1990. “This second molecular zipper is double trouble. Once it’s zipped, it’s zipped, and once the formation of fibrils starts, it looks like you can’t stop it. The kinked form initiates a dangerous cascade of events that we believe can result in Alzheimer’s disease.”

Why does beta amyloid’s 23rd amino acid sometimes form this dangerous kink?

Clarke thinks the kinks in this amino acid form throughout our lives, but we have a protein repair enzyme that fixes them.

“As we get older, maybe the repair enzyme misses the repair once or twice,” he said. “The repair enzyme might be 99.9% effective, but over 60 years or more, the kinks eventually build up. If not repaired or if degraded in time, the kink can spread to virtually every neuron and can do tremendous damage.”

“The good news is that knowing what the problem is, we can think about ways to solve it,” he added. “This kinked amino acid is where we want to look.”

The research offers clues to pharmaceutical companies, which could develop ways to prevent formation of the kink or get the repair enzyme to work better; or by designing a cap that would prevent fibrils from growing.

Clarke said beta amyloid and a much larger protein tau — with more than 750 amino acids — make a devastating one-two punch that forms fibrils and spreads them to many neurons throughout the brain. All humans have both beta amyloid and tau. Researchers say it appears that beta amyloid produces fibrils that can lead to tau aggregates, which can spread the toxicity to other brain cells. However, exactly how beta amyloid and tau work together to kill neurons is not yet known.

In this study, Warmack produced crystals, both the normal and kinked types, in 15 of beta amyloid’s amino acids. She used a modified type of cryo-electron microscopy to analyze the crystals. Cryo-electron microscopy, whose development won its creators the 2017 Nobel Prize in chemistry, enables scientists to see large biomolecules in extraordinary detail. Professor Tamir Gonen pioneered the modified microscopy, called microcrystal electron diffraction, which enables scientists to study biomolecules of any size.

Eisenberg is UCLA’s Paul D. Boyer Professor of Molecular Biology and a Howard Hughes Medical Institute investigator. Other researchers are co-author Gonen, a professor of biological chemistry and physiology at the UCLA David Geffen School of Medicine and a Howard Hughes Medical Institute investigator; and Jose Rodriguez, assistant professor of chemistry and biochemistry who holds the Howard Reiss Career Development Chair.

The research was funded by the National Science Foundation, National Institutes of Health, Howard Hughes Medical Institute, and the UCLA Longevity Center’s Elizabeth and Thomas Plott Chair in Gerontology, which Clarke held for five years.

This article originally appeared in the UCLA Newsroom.

Photo of baby laughing

Babies Know the Difference between the Laughter of Friends and Strangers

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Five-month-olds may use chuckles to identify information about social interactions

Photograph of baby laughing

Credit: Aarti Kalyani Getty Images

Most people can share a laugh with a total stranger. But there are subtle—and detectable—differences in our guffaws with friends.

Greg Bryant, a cognitive scientist at the University of California, Los Angeles, and his colleagues previously found that adults from 24 societies around the world can distinguish simultaneous “co-laughter” between friends from that between strangers. The findings suggested that this ability may be universally used to help read social interactions. So the researchers wondered: Can babies distinguish such laughter, too?

Bryant and his fellow researcher Athena Vouloumanos, a developmental psychologist at New York University, played recordings of co-laughter between pairs of either friends or strangers to 24 five-month-old infants in New York City. The babies listened longer to the laughs shared between buddies—suggesting they could tell the two types apart, according to a study published in March in Scientific Reports.

The researchers then showed the babies short videos of two people acting either like friends or strangers and paired those with the audio recordings. The babies stared for longer at clips paired with a mismatched recording—for example, if they saw friends interacting but heard strangers laughing.

“There’s something about co-laughter that is giving information to even a five-month-old about the social relationship between the individuals,” Bryant says. Exactly what components of laughter the infants are detecting remains to be seen, but prior work by Bryant’s team provides hints. Laughs between friends tend to include greater fluctuations in pitch and intensity, for example.

Such characteristics also distinguish spontaneous laughs from fake ones. Many scientists think unprompted laughter most likely evolved from play vocalizations, which are also produced by nonhuman primates, rodents and other mammals. Fake laughter probably emerged later in humans, along with the ability to produce a wide range of speech sounds. The researchers suggest that we may be sensitive to spontaneous laughter during development because of its long evolutionary history.

“It’s really cool to see how early infants are distinguishing between different forms of laughter,” says Adrienne Wood, a psychologist at the University of Virginia, who was not involved in the study. “Almost every waking moment is a social interaction for [babies], so it makes sense that they are becoming very attuned to their social worlds.”

This story originally appeared in the Scientific American.

Coretta Harris, left, chair of the 2019 Gold Shield Faculty Prize Committee; Paul Barber; and Karen Sears, ecology and evolutionary biology department chair, who nominated Barber for the award.

Marine scientist Paul Barber named 2019 Gold Shield Faculty Prize winner

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Coretta Harris, left, chair of the 2019 Gold Shield Faculty Prize Committee; Paul Barber; and Karen Sears, ecology and evolutionary biology department chair, who nominated Barber for the award.

Coretta Harris, left, chair of the 2019 Gold Shield Faculty Prize Committee; Paul Barber; and Karen Sears, ecology and evolutionary biology department chair, who nominated Barber for the award.

 

In the very first day of his “Introduction to Marine Science” class, Paul Barber tells his students an amusing story about himself. It has to do with how a guy from Tucson, Arizona — in the middle of the Sonoran Desert — became a marine scientist.

Full of twists and turns, the story is also an inspiring one. It tells how Barber, a professor of ecology and evolutionary biology, grew up in a low-income family and attended an inner-city middle school where he once had a .45 caliber handgun pointed at his head.

“It was in the middle of class, and my teacher never even noticed,” Barber said.

Military recruiters, not college recruiters, came to Barber’s high school. But he studied hard and won a full-ride Flinn Foundation scholarship, which enabled him to attend the University of Arizona. His interest in terrestrial evolutionary genetics was sparked by classes in animal behavior and herpetology, which is the study of amphibians and reptiles. Yet it took a roundabout series of adventures while he was a graduate student at UC Berkeley — involving frogs, mongooses, hyenas, clownfish and mantis shrimp — to bring him to his current position at UCLA.

“The punchline I tell the students is that, here I am, teaching a marine science course, and I’ve never taken a marine science course in my entire life,” Barber said. “And the fact that they are in that class means that they are so much further ahead of where I was at this point in their studies. If I can do this, never having done a marine science course in my life, then they are well-positioned to succeed.”

It’s this humility that endears Barber to both his students and his peers, several of whom endorsed him for the 2019 Gold Shield Faculty Prize — a $30,000 award presented annually by Gold Shield, Alumnae of UCLA, to an exceptional mid-career full professor with a distinguished record of undergraduate teaching, research and university service.

Almost since his arrival at UCLA in 2008, Barber has served as the director of the Program for Excellence in Education and Research in the Sciences, known as PEERS, a two-year program for outstanding students who wish to pursue careers in the life or physical sciences. In particular, PEERS emphasizes the recruitment and retention of students from groups traditionally underrepresented in science. Studies of the program show that its students are nearly twice as likely to complete a science degree and earn better grades than similar students not in PEERS.

Equally impressive is a summer program Barber founded 16 years ago, The Diversity Project, that he now runs with UCLA colleague Peggy Fong, also a professor of ecology and evolutionary biology. The Diversity Project is designed to increase diversity in marine science — a field with a very low percentage of traditionally underrepresented minorities — and provides undergraduate students with opportunities to conduct research outside the United States, ultimately inspiring them to continue in marine science.

“We go to amazing places, like Indonesia, that have the most diverse and spectacular coral reefs on the planet,” Barber said. Nearly 70% of program alumni go on to graduate school. Among the schools from which they have earned degrees: Harvard, Stanford, UC Santa Cruz, the Scripps Institution of Oceanography and UCLA.

“Dr. Barber is a strong mentor, and I know for a fact that I am a stronger scientist because of his support,” said Camille Gaynus, an alumna of The Diversity Project. “His mentorship is embedded in me, and I strive to pass on the same sentiments to the undergrads and high school students I currently mentor. Because of Dr. Barber, I know I will become a professor and continue to provide opportunities to young scientists, particularly Black females like myself.”

Photo of Alan Casatel

UCLA psychologist on why we should embrace aging

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UCLA Broadcast Studio

Alan Castel notes that wisdom and creativity tend to flourish with age.

Who says that growing old must be paired with mental decline? Not Alan Castel, professor of psychology in the UCLA College. Our brain’s ability to adapt as we age, can actually lead to the improvement of some types of memory.

“Getting older doesn’t have to be about aches and pains and memory loss,” says Castel, who recently wrote a book about the psychology of successful aging. “If we take care of ourselves physically and choose to focus on remembering the good things, we lay the groundwork for a long and happy life.”

People coming to UCLA Alumni Day on May 18 can attend a conversation with Castel at 2:30 p.m., during which he’ll share some of what goes into successful aging.