All By Myself

THE COGNITIVE HEALTH IMPACT OF CHRONIC SOCIAL ISOLATION

Among the many hard lessons learned during the pandemic was the impact of social isolation. It showed up most
vividly in the heartbreaking stories of elderly people living
in long-term care facilities who were cut off from their famlies. But it is a phenomenon that hurts people of all
ages and in many ways.

Researchers have long believed that isolation early in life can have damaging long-term consequences, including an elevated risk of social anxiety disorder, which the U.S. National Institute of Mental Health defines as “an intense, persistent fear of being watched and judged by others. This fear can affect work, school, and other daily activities. It can even make it hard to make and keep friends.”

Finding new ways of treating social anxiety disorder is a focus of Dr. Derya Sargin’s work. The University of Calgary researcher is studying how social isolation among young people affects the brain at the cellular level.

“The brain is so central to our being and our functioning. My main goal is to understand how the brain functions so we can develop effective treatments. That’s the main thing that draws me to this research,” Dr. Sargin told Mind Over Matter®.

Supported by a 2020 Future Leaders in Canadian Brain Research grant from Brain Canada, the assistant professor in the Faculty of Arts’ Department of Psychology is conducting her research by undertaking detailed studies of the brain cells, or neurons, of mice.

Through this work, Dr. Sargin and her colleagues deprive rodents of regular social contact during adolescence and then observe them as they develop behaviours that roughly mimic social anxiety in humans. Already, her team has made an important and exciting discovery.

WE FOUND A GROUP OF CELLS THAT ARE CRITICAL FOR SOCIAL INTERACTION, AND WE ALSO FOUND THAT THE ACTIVITY OF THESE CELLS IS COMPROMISED WHEN ANIMALS ARE ISOLATED.

The next step for her and her team is to explore the possibilities of interventions. “We’re studying how can we specifically target those circuits and improve social behaviour.”

This project is one of three Brain Canada–funded studies exploring aspects of brain cell function in which Dr. Sargin leads or participates as a team member.

The second, co-funded by the Alzheimer’s Association International Research Grant Program, focuses on serotonin, Alzheimer’s disease (AD), and sex differences. Serotonin is a chemical released by neurons that is central to social, cognitive, and mood regulation. A severe loss of serotonin neurons has been seen in the early stages of AD, often before the disease is diagnosed.

THIS EARLY DISRUPTION IN THE BRAIN’S SEROTONIN SYSTEM HAS BEEN ASSOCIATED WITH SYMPTOMS LIKE MOOD CHANGES AND SOCIAL IMPAIRMENTS, WHICH CAN BE SEEN MUCH EARLIER THAN THE MEMORY DIFFICULTIES ASSOCIATED WITH AD.

While the contribution of the serotonin system seems to be critical in AD progression, scientists do not yet know why this disruption happens or how it may contribute to the progression of dementia.

She and her colleagues are using mouse models to study how serotonin neuron dysfunction affects the progression of the disease and whether stimulating serotonin circuits can improve behaviour. Exploring sex differences is a central part of the research.

“For example, we found that if you inhibit one neural pathway you can disrupt social behaviour with one sex but not the other. So that’s why we’re trying to delve into these specific circuits to characterize which is more relevant for which sex. Of course, it’s very important in terms of coming up with treatment approaches for all genders,” said Dr. Sargin.

Sex differences have historically been understudied, and she points out that studies that do consider them are more expensive because researchers need more lab animals.

“That’s why organizations like Brain Canada, especially with their grants for early career researchers, have been critical for establishing our labs, for getting published and for doing the kind of research I want to do. I’m very grateful,” she said.

Dr. Sargin is a team member of a third Brain Canada–funded study, which is also supported by Women’s Brain Health Initiative (WBHI). It is led by Dr. Jonathan Epp, an associate professor in the Department of Cell Biology and Anatomy at the University of Calgary (who also happens to be her life partner).

We know that females with AD tend to exhibit faster cognitive decline than males. To better understand this trend, the study by Drs. Epp and Sargin aims to pinpoint potential mechanisms that may be involved.

Using a specialized imaging technique, they can observe the activity of a specific group of neurons in the brains of female and male mice as the animals undergo a series of memory tests.

Through this testing, the researchers have observed that the activity of those neurons in females is impaired much earlier in the progression of AD than it is in males.

By stimulating or blocking this group of neurons with light, the researchers can increase or decrease their activity and observe its effect on the animal’s behaviour. The effect is telling.

“Using light to stimulate these neurons allows us to enhance learning and memory function in the females and, likewise, if we go into the males and inhibit those neurons, we can impair memory to the same sort of extent that we see in the female mice,” said Dr. Epp. “We think these neurons play an important role in the early cognitive impairments that are occurring in females.”

Dr. Sargin says the implications are important: “If we can understand the underlying mechanisms, we can develop therapeutic interventions.”

Dr. Epp echoed Dr. Sargin’s gratitude for the funding support. “Looking back on the first six years of my career, I’m not sure how I would have done it without these grants from Brain Canada. They had such a phenomenal impact on getting this research done. I don’t think we could have done it otherwise,” said Dr. Epp.

“We are proud to support groundbreaking research projects like this one, which sheds light on critical sex differences in brain function. This work has the potential to significantly impact our understanding of diseases like Alzheimer’s and pave the way for targeted therapeutic interventions,” said Dr. Viviane Poupon, President and CEO of Brain Canada.

WBHI Founder and President Lynn Posluns added, “Their research into sex differences in the brain is exactly the kind of project WBHI was founded to support. They ask essential questions that have been neglected for far too long.”

To learn more about Brain Canada and the research it funds, visit braincanada.ca.

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