Human Glymphatics · Effects of sleep deprivation and adrenergic inhibition on glymphatic flow in humans

Effects of sleep deprivation and adrenergic inhibition on glymphatic flow in humans

Sleep problems and disordered sleep is highly prevalent in modern society and may lead to a range of diseases including obesity, cardiovascular problems and Alzheimer’s Disease. Nevertheless, the molecular and biological underpinnings of why we sleep remain poorly understood. Recent preclinical evidence show that while rodents are asleep, cardiovascular pulsations driven an influx of cerebrospinal fluid into the brain parenchyma that generates a connective fluid flow that effectively promotes the removal of metabolic by-products that has accumulated during the day. This sleep dependent macroscopic pathway may be one of the reasons why we need to sleep and why insufficient sleep is detrimental to the organisms. The aim of this project is to investigate whether such macroscopic clearance exists in the human brain during sleep and whether it has relevant biological consequences for performance and cognition. To investigate these questions, we set up a human sleep study using novel, state of the art ultra-fast magnetic resonance imaging (MRI) protocols, including multiband and magnetic resonance encephalography (MREG). These MR sequences enabled us to acquire images of the entire human brain at 5-10 times each second. By applying these novel imaging methods I aimed at: 1. addressing how cardiac driven brain pulsations in the brain change between sleep and wakefulness; 2. whether levels of brain pulsations are associated with sleep intensity; and 3. Whether the brain pulsations and clearance can be enhanced by adrenergic antagonists similar to what has been shown in rodents. Secondly, while data collection for the primary study was ongoing, we investigated data related to brain clearance in an already collected cohort of healthy controls who underwent a controlled sleep deprivation protocol. The protein transporter aquaporin-4 has been shown to play a critical role in facilitating the influx of CSF from perivascular spaces during sleep. We therefore set out to investigate whether common genetic variants of the aquaporin-4 gene modulate sleep and sleep-wake behavior in this cohort, which would provide further evidence of a sleep driven and aquaporin-4 dependent pathway in humans.

Data: CORDIS, © European Union