My name is Savannah (Sav) Turton, and I am a member of Dr. Paul Murphy’s lab. When I first joined Dr. Murphy’s lab about a year and a half ago, I was an undergraduate student studying biology with a focus in genetics, genomics, and bioinformatics, but I have since graduated with my degree. Despite focusing on genetics in my undergraduate years, my goal is to soon apply to the Integrated Biomedical Sciences program here at UK to pursue a PhD in either neuroscience or biochemistry. For now, I am taking a few non-degree courses in order to further my understanding of what we work on in the lab.

My name is Sam Padgett, and I also started working in Dr. Paul Murphy’s lab around a year and a half ago. I am from Berea, Ky., and am currently a junior here at UK, majoring in human health sciences with a minor in neuroscience. After graduation, I hope to gain some additional research and health care experience and apply to MD/PhD programs following a gap year or two. A few years ago, I never would have expected to get into research, but it has turned into something important to me that I truly enjoy devoting my time to. The process of discovering things previously unknown to the world is so exciting to me, and the research I’ve done while here in Dr. Murphy’s lab has inspired me to continue pursuing research.

We both entered Dr. Murphy’s lab together because we were fascinated by the brain and interested in learning more about the interactions between sleep patterns and Alzheimer’s disease (AD). Throughout our time here, though, we also began to understand the full extent to which women have been excluded from research studies across all fields. Unfortunately, this includes research like ours involving AD, despite the fact that two-thirds of AD patients are biologically female. However, our lab, among many others, is beginning to focus on studying how sex interacts with sleep and AD. As women, we are driven to investigate sex differences in our research to help eliminate this inequity for future generations and to better understand why AD affects women so much differently and more frequently than men.

Recent studies in our lab have shown that chronic sleep disruptions in mice affect the development of AD pathology, and there is a significant sex difference in both the amount of AD-related pathology and in the response to the sleep disruption (also called sleep fragmentation, or SF) itself. Typically, the female mice have more amyloid-beta (Aβ) pathology than the males, and they show a large increase in dark phase ‘rebound’ sleep after undergoing SF treatment — despite also displaying a significant decrease in overall sleep. Our research has focused on whether the activity of the enzyme γ-secretase has an influence on both the sex differences we observed in AD pathology and the differences observed regarding response to sleep fragmentation.

In order to inhibit γ-secretase in the mice, we administered a drug called Semagacestat every evening for four weeks. Two weeks into the study, we started recording the baseline sleep patterns of the mice. SF was conducted for five days and consisted of 4 daily sleep disruptions of 1-hour intervals, during which our mice were kept awake with novel objects (Legos) and gentle stimulation using a paintbrush. Our studies show that SF significantly increased overall sleep regardless of sex, but this effect was primarily driven by an increase in dark-phase sleep in the males treated with Semagacestat. We also noted a significant reduction in Aβ in the male mice, which could be due to increased sleep resulting in more efficient Aβ clearance.

Our results were unexpected because they were quite different from what we had seen in our other studies – normally, we see that the females drive the increase in dark phase sleep and Aβ pathology. It is possible that the timing of the drug treatment could have affected the outcome, as the drug was administered in the evening before the dark phase. Also, the SF protocol was much shorter than the one our lab has used in previous studies. We are very curious as to why this sex difference seemed to flip in our experiment as compared to the others performed in our lab. In the future, we hope to alter the time at which we administer the drug and change the length of the SF period. Overall, the female mice appeared somewhat resistant to the Aβ-lowering effect of the drug. We believe this observation may be related to females usually having more Aβ pathology overall, which aligns with human cases where women tend to have worse or more aggressive AD neuropathology.

In March, we were given the opportunity to present our research at the AD/PD conference in Gothenburg, Sweden. It was truly one of the best experiences, and we are really looking forward to learning more with Dr. Murphy, the department of molecular and cellular biochemistry, and the Sanders-Brown Center on Aging.