Scientists know that social isolation can alter brain structure and lead to the breakdown of myelin, the fatty coating that insulates nerve fibers in the brain. But they don’t yet know exactly how or why it happens.
A new, five-year study, supported by the National Science Foundation, investigates the potential mechanisms that drive the process. “We’re looking at the role of dopamine in regulating changes in myelin caused by social isolation,” said study leader Leora Yetnikoff, a professor of Biology and a member of the CUNY Neuroscience Collaborative at the CUNY Graduate Center, and a professor of psychology at the College of Staten Island.
Yetnikoff was recently awarded a $1 million NSF CAREER award to examine how dopamine affects oligodendrocytes, the specialized cells in the brain and spinal cord that make myelin. Using advanced genetic and imaging tools, her team will observe how dopamine interacts with these cells and whether changing dopamine levels can reverse the effects of social isolation on myelin.
“Traditionally, myelin is believed to be an insulator of axons,” Yetnikoff said, referring to the long and slender nerve fibers that carry messages from neuron to neuron using electricity. The myelin coats axons much like insulation on a wire, paving the way for these electrical signals to travel faster for better communication.
However, newer research focuses on oligodendrocytes as metabolic supporters, supplying the molecules to help power electrical signals traveling through axons in the brain. And without this support, axons can weaken or degenerate, the professor said.
So, the question people are starting to ask is, ‘What other functions are these cells playing besides producing myelin?”
Leora Yetnikoff, study leader
The project will focus on three areas.
“One is a novel rule for dopamine, which is viewed as a key neurotransmitter involved in synaptic plasticity,” she said, referring to the brain’s ability to strengthen or weaken the connections between neurons and how the brain changes with experience – making learning, memory, and adaptation possible.
“The work that we’re doing suggests – and we haven’t proven it yet – that dopamine may be communicating with the oligodendrocytes to make myelin plastic, and that’s a novel form of plasticity in the brain.”
The second looks at the broader implications of dopamine’s effect on myelin in the brain. “Social isolation is only one phenomenon that causes changes in myelin plasticity,” said Yetnikoff, pointing to brain injury and neuropsychiatric conditions such as schizophrenia and addiction. “Dopamine is involved in all these conditions. Right now, we’re just looking at social isolation, but the implications are that it could potentially be involved in many other conditions.”
The third area relates to social isolation and the external factors that cause it.
“So, we’ve just come out of the COVID pandemic,” said the professor, “and there’s social isolation among the elderly. It can occur in youth, when they lock themselves up with video games and computers. So, how is that affecting the brain and what are the mechanisms involved?”
Since the 1960s, animal studies have shown that social isolation can result in altered levels of dopamine, the neurochemical most linked to motivation and pleasure. Yet, scientists are only beginning to piece together the connections between dopamine and myelin plasticity.
Yetnikoff points to a seminal study, which tracked more than 100 children in Romanian orphanages. The researchers found that neglect and psychosocial deprivation led to abnormal brain development in the orphans, especially in the prefrontal cortex, responsible for higher-level cognitive function and impulse control. “That work showed that myelination in their prefrontal cortex, as well as other myelinated tracts, was decreased compared to non-neglected orphans,” she said.
If her study can identify the mechanisms involved in demyelination that occurs with social isolation, she said, there’s potential to gain critical insights on other conditions seen with the deterioration of myelin – drug addiction, multiple sclerosis, Parkinson’s Disease, and other neuropsychiatric diseases among them.
Student researchers will train in the Yetnikoff Laboratory, using cutting-edge technology over the five-year-life of the project. Yetnikoff credits her students for doing much of the work that went into the proposal that won the NSF grant. “None of this would’ve happened without them,” she said.
Yetnikoff received a young investigator grant from the Brain and Behavior Research Foundation for her work on dopamine and adolescence in 2017, and a SCORE Award from the National Institutes of Health for her research on glial cells in 2021. She was granted the CUNY Feliks Gross award for outstanding research in 2022.
Source:
The Graduate Center, CUNY