An electronic copy of the thesis may be ordered from the faculty up to 2 days prior to the public defence. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Trial Lecture – time and place
See Trial Lecture.
- First opponent: Professor Christian Henneberger, University of Bonn
- Second opponent: Professor Hjalmar Brismar, KTH Royal Institute of Technology Stockholm
- Third member and chair of the evaluation committee: Associate Professor Johanne Egge Rinholm, University of Oslo
Chair of the Defence
Professor Reidar Tyssen, Faculty of Medicine, University of Oslo
Associate Professor Rune Enger, Faculty of Medicine, University of Oslo
Research from the 15 years has also shown that astrocytes – a type of support cell in the brain – play important roles in sleep. One of those roles is helping cleanse the brain of waste products that could cause brain disorders such as Alzheimer’s disease and Parkinson’s disease. The aims of this thesis were to develop new tools to study astrocytes in sleep, employ these tools to study astrocytic calcium signaling across the sleep states, and to identify possible mechanisms by which astrocytes modulate brain waste clearance.
We studied astrocytic calcium signaling by two-photon microscopy in naturally sleeping head-fixed mice, and found reduced calcium signaling in sleep compared to wakefulness. Genetically modified mice with reduced calcium signaling had disrupted slow-wave sleep in the form of awakenings and perturbed brain rhythms. Moreover, astrocytic calcium signals typically increased before any other sign of awakening, indicating that the astrocytic calcium signals play a key role in the transition from the sleeping to the awake state. Mice with reduced calcium signals also displayed a significant increase in so-called sleep spindles. Such sleep spindles are associated with memory consolidation and intelligence, but an increasing amount of sleep spindles are associated with learning difficulties.
The perivascular spaces are fluid-filled compartments surrounding arteries and arterioles of the brain confined by specialized astrocytic processes called endfeet. Perivascular spaces are routes from which fluid may enter the brain tissue, and in the process wash out waste products. We demonstrated that the size of the perivascular spaces changed with sleep state-specific vascular dynamics, and hypothesize that the cycling of sleep states is important for proper brain waste clearance. These findings may have implications for our understanding of neurodegenerative disorders such as Alzheimer’s disease.
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