Translating Sleep and Memory
Understanding the neuroscience of sleep deprivation and memory formation
By Molly Grab ’17
It’s an everyday phenomenon that takes many forms: all-night study sessions, late nights at the office or midnight wake-up calls from young children. While sleep deprivation may seem commonplace, the CDC reports that it is a true public health crisis affecting more than a third of all Americans.
It’s also what intrigues neuroscientist Jennifer Choi Tudor, Ph.D., assistant professor of biology, who was honored recently by the Sleep Research Society as an Outstanding Early Investigator (honorable mention) for her 2016 Science Signaling paper on the connection between sleep deprivation, memory and a little-known protein called 4E binding protein 2 (4EBP2). Tudor is the lead author of the paper.
“Sleep deprivation can lead to a whole host of issues,” Tudor explains. “It can affect metabolism, the processing of waste and gene expression. But we showed that, of particular importance, sleep deprivation impairs the critical process to make the necessary proteins to form memories, also known as translation.”
"... sleep deprivation impairs the critical process to make the necessary proteins to form memories ..."
Jennifer Choi Tudor, Ph.D.
While it’s widely accepted that protein synthesis in the brain fuels memory function, the mechanical relationship between protein synthesis and sleep is much less clear. Prior to joining Saint Joseph’s faculty in 2016, Tudor shed light on this subject as a postdoctoral research fellow at the University of Pennsylvania.
By comparing the brain function of both sleep-deprived and well-rested lab mice, Tudor found that just five hours of extended wakefulness resulted in significant memory deficits.
“That’s the equivalent of someone who usually goes to bed around 11 p.m. staying up until 3 a.m.,” Tudor says.
Following sleep deprivation, memory deficits occur because the process to make proteins is impaired in a region of the brain called the hippocampus, which is associated with memory. The molecular machinery for protein synthesis is governed by an insulin-signaling pathway, and sleep deprivation causes changes in a specific subset of that pathway. Tudor found that by manipulating this pathway, the molecular setup for protein synthesis remained intact, reducing sleep deprivation’s adverse effects on memory formation.
To accomplish this, Tudor injected a virus that increased the abundance of the 4EBP2 protein into the hippocampus of mice, which fully restored protein synthesis — even when they were sleep deprived — as well as memory function.
“What we found is that even though the mouse is sleep deprived, because plenty of the protein synthesis was there and the machinery was available, we were able to prevent memory deficits,” Tudor explains.
In her lab at Saint Joseph’s, comprised of a team of graduate and undergraduate assistants, Tudor is building on this finding by asking new questions about how sleep affects memory. Her work focuses on gaining a better understanding of the 4EBP2 protein and its role in the insulin-signaling pathway.
One of the questions she is now considering involves memory and enhanced sleep: Can it alter the insulin- signaling pathway, boost the protein synthesis machinery, and potentially improve memory function?
“If we work with an Alzheimer’s disease mouse model that already has memory impairment, and we make their sleep ‘better’ or give them more sleep, can we then increase protein synthesis enough so that they’ll have improved memory function?” Tudor asks.
While her research considers the possibility of enhancing sleep — and ultimately, memory — by performing protein-level analyses, Tudor is conversely exploring whether or not modified 4EBP2 proteins can produce memory deficits if injected into well-rested organisms. Answering this question could lead to a better understanding of 4EBP2’s role in memory formation.
In addition to her work with memory, Tudor and her students are currently preparing a manuscript describing a neurodevelopmental disorder linked to faulty insulin signaling known as Fragile X Syndrome, a single-gene disorder that causes autism. According to Tudor, the study yielded a surprising finding about the mouse model used by many Fragile X researchers.
“Our data reveal that the mice do not have many of the autism-related behaviors evident in prior studies, like problems with social interaction and repetitive behaviors,” says Tudor. “Researchers need to be aware that it’s a difficult model with which to work.”
As her research on the intersection of memory, sleep and disease continues, Tudor is hopeful that she and her students can make a difference in the lives of those with neurodegenerative diseases or careers that cause insufficient sleep, such as military and health care professions.
“The silver bullet would be if we could come up with some sort of drug or pharmaceutical agent that could keep the memory there, or help create the memory, even though one is sleep deprived,” Tudor says.
She knows that, even if this idea is relegated to the future, in the meantime, her lab serves an important role.
“The goal is that we do good science, learn something new in the process, and then share that with my students, now and in the future,” Tudor says.