Branco Weiss Fellow Since
2023
Research Category
Biology, Neuroscience
Research Location
VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, Belgium
GIGA-CRC in Vivo Imaging, University of Liège, Belgium
Background
When we are about to fall asleep, our body starts offloading heat through vasodilation in hands and feet. These sleep-associated changes in temperature regulation suggest that our body and brain are actively set to cool down at sleep initiation. Brain temperature does indeed decrease during sleep, as shown in many different mammalian species to date, and likewise, a lack of sleep keeps brain temperature elevated.
Acute sleep disruption impairs memory formation, and chronic sleep disruption has even more detrimental effects: it is associated with an increased risk of developing neurodegenerative diseases. Interestingly, a reduction in brain temperature is used in the clinic as a neuro-protectant. Could the daily decrease in brain temperature we experience at night serve a neuro-protecting function? And when brain temperature does not decrease at night such as during sleep loss, are we at increased risk of developing neurodegenerative diseases?
Details of Research
Dr. Marieke Hoekstra will use three different models to investigate the function of sleep-dependent changes in brain temperature. First, she will focus on temperature-sensitive proteins that change their levels with sleep-wake state. In genetically manipulated mice, she will induce expression of these proteins during sleep loss, and then test to what extend sleep-loss induced memory impairment can be rescued by overexpression of these temperature-sensitive proteins. Second, Dr. Hoekstra will manipulate the temperature of human induced neurons to mimic sleep-wake cycles. To understand the impact of these sleep-dependent temperature cycles on the function of human neurons, she will then assess how well the neurons are connected, what their activity profile looks like, and if there are changes in the build-up of toxic proteins such as tau. Last, it is not known whether the nightly decrease of the temperature of the human brain is driven by sleep, like it is in other mammals. To close this knowledge gap, Dr. Hoekstra will use a combination of brain imaging and EEG-based techniques to, for the first time in humans, determine both brain temperature and sleep-wake state simultaneously.
This research has the potential to fundamentally alter the way we understand sleep – not only as a profound change in neuronal activity, but as a state in which brain temperature is actively downregulated, thereby contributing to the function of sleep. Moreover, the results of these experiments could contribute to the development of tools to counteract the negative consequences of sleep loss, e.g. by manipulating brain temperature or temperature-sensitive molecular pathways.
