The brain is often colloquially divided into white and grey matter. White matter is so named because the neurons in white matter are ensheathed in a fatty, white substance called myelin. Myelin is crucial for proper neuronal signaling, and its dysregulation and loss are associated with several neurological conditions, including Alzheimer’s disease (AD). In the brain, the cells responsible for producing and maintaining myelin are called oligodendrocytes. Dr. Gibson is a renowned expert in oligodendroglia and investigates the role of sleep and circadian rhythms in their development and function. She also studies how sleep and circadian disruptions affect oligodendroglia in the context of AD, and whether these changes contribute to disease progression. Here, she hypothesizes that the disruption of circadian rhythms in oligodendroglia leads to disrupted myelin, fractured sleep patterns, and cognitive deficits, and that these deficits are specifically mediated by changes in calcium signaling in neurons.
This project has two experimental aims. In the first, Dr. Gibson’s team will build on prior findings from mouse models, showing that the loss of circadian rhythms in oligodendroglia from amyloid mice accelerates changes associated with disrupted sleep. Her team will now study amyloid mice to define exactly how the loss of circadian rhythms alters sleep patterns over an extended timeframe and how they may feed into one another. The second aim will focus on the role of calcium signaling in this interaction. Calcium signaling is a major marker of activity and overall cellular health, making it a valuable experimental endpoint. Dr. Gibson’s previous studies led her to hypothesize that the negative impacts of circadian disruptions in oligodendroglia are mediated by disruptions in their calcium signaling. She has identified altered oligodendroglial calcium signaling in human AD OPCs, precursors to fully matured oligodendrocytes, and will now test how amyloid pathology in mice affects this calcium signaling and sleep. This aim will help define a specific pathway that could be therapeutically targeted to correct sleep disruptions associated with AD.
Overall, this project will examine the role of circadian disruptions in oligodendroglia in the progression of AD and amyloid pathology and establish oligodendroglial calcium signaling as a potential therapeutic target.
