A Pathway to Better Sleep?

What with our smart phones and high-speed internet and social media and overstuffed work and school schedules, our hectic 21st century civilization never slows down.  So it's not surprising that many of us don't get nearly enough sleep.  But lack of sleep isn't merely an annoyance.  Scientific evidence links sleep deprivation to a range of significant short-term cognitive impairments such as memory loss, slower psychomotor reflexes and diminished attention.  These affect us not only individually but on a societal level, leading to more accidents, workplace errors, and decreased efficiency.

But it might be possible to mitigate some of sleep deprivation's deleterious effects by achieving a better understanding of precisely what it does to the brain on a molecular level.  Emily Davis, a sophomore in Penn's Biological Basis of Behavior (BBB) program, spent ten weeks this summer studying how an important cellular signaling pathway in the brain is affected by sleep deprivation and its effects on memory.

Working under post-doctoral fellow Jennifer H.K. Choi in the lab of BBB program co-director and Brush Family Professor of Biology Ted Abel, Davis focused on the mTOR (mammalian Target of Rapamycin) pathway in the hippocampus, a brain structure vital in memory processing and consolidation.  Her work was an outgrowth and continuation of a paper published by Abel and Choi earlier this year in Physiological Genomics, a study spearheaded by a former graduate student in Abel’s lab, Christopher Vecsey. They examined the effects of sleep deprivation on the mTOR pathway in mice.

After we have a good idea of what proteins within that pathway are being changed and altered, we could see if we can artificially increase 4EBP or other protein levels within mice in the hippocampus. If that's possible, we might be able to reverse the effects of sleep deprivation on memory and synaptic processes. - Emily Davis

"Basically we wanted to further investigate the protein levels specific to the mTOR pathway and see what happens to them during sleep deprivation," Davis explains.  "So what I did for my project was conduct protein analyses by Western blotting and enzyme-linked immunosorbant assays, which allows us to look at the different protein concentration levels within the samples so we're able to compare the amount of protein in sleep-deprived and non-sleep-deprived mice."

Davis examined tissue samples from the hippocampi of both groups, measuring total and phosphorylated mTOR levels as well as some other proteins involved in the mTOR signaling pathway such as 4EBP.  She also looked at several proteins unrelated to mTOR "to show that those were not changing, so that we could really show that it's the mTOR signaling pathway and the proteins involved with that that are affected by the sleep deprivation."

Davis found that the sleep-deprived mice displayed decreased phosphorylated 4EBP levels, indicating a definite disruption in the mTOR signaling pathway.  She observed no significant change in the non-mTOR-related protein levels, indicating that mTOR is indeed the pathway affected by the sleep deprivation. 

It's an important piece of the puzzle, but Davis emphasizes that it's only a first step.  Many more proteins need to be investigated.  "The next step is to continue looking at these different proteins involved in the mTOR pathway," she says.  "After we have a good idea of what proteins within that pathway are being changed and altered, we could see if we can artificially increase 4EBP or other protein levels within mice in the hippocampus."  If that's possible, she explains, "We might be able to reverse the effects of sleep deprivation on memory and synaptic processes."

Davis became involved in the research through the Penn Undergraduate Research Mentoring Program (PURM), an initiative that gives undergraduate students the opportunity to spend a summer as a research assistant for a faculty member.  It's a chance for a first- or second-year undergraduate to participate in cutting-edge research that would normally be open only to graduate students, with a Penn professor as an active mentor. 

"When I came to Penn I knew I wanted to do some sort of brain research," says Davis.  "I happened to come across this project with PURM, and I took an interest in it because sleep deprivation is something that happens to a lot of people, especially in this modern era.  It can affect our overall condition from a cellular level all the way up to our own cognition.  It's an important area of study and, from a personal standpoint, it's a great opportunity to be able to do this.  It's exciting."