The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Click here to participate in the public defence
Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Denali Fellow & Adjunct Associate Professor Robert G. Thorne, Denali Therapeutics & The University of Minnesota
- Second opponent: Assistant Professor Jillian Stobart, University of Manitoba
- Third member and chair of the evaluation committee: Professor II Bjørnar Hassel, University of Oslo
Chair of the Defence
Professor Mathias Toft, University of Oslo
Principal Supervisor
Associate Professor Rune Enger, University of Oslo
Summary
We spend a third of our lives sleeping, yet the functions of sleep are still one of the biggest mysteries in biology.
Most of sleep research is focused on neurons, yet studies suggest that a non-neuronal cell type – the glial cells called astrocytes – are also important for proper sleep and sleep dependent processes, such as brain waste clearance. The mechanisms and the molecular underpinnings that astrocytes employ to mediate these sleep-dependent functions remain elusive.
The aims of the thesis to investigate whether astrocytic Ca2+ signals are involved in sleep regulation and to investigate whether sleep state specific vascular movement could provide a mechanism for brain waste removal enhancement upon sleep by two-photon microscopy of naturally sleeping mice; and to delineate molecular underpinnings of brain waste clearance by radioactive tracer assays.
Astrocytic Ca2+ signaling was reduced during sleep as compared to when the mice were awake. However, there was still remaining activity during sleep which displayed different features across the sleep states and was found to be important to assure proper slow wave sleep. Mice with perturbed astrocyte Ca2+ signaling had more short awakenings and shifted from one sleep state to another more often, which interrupted their slow wave sleep and reduced its quality.
Removal of waste from the brain is facilitated by cerebrospinal fluid fluxes in the perivascular space – an area between astrocytic endfeet and blood vessel wall. We found that different sleep states are associated with specific arteriolar vasomotion patterns coupled to inverse perivascular space changes, that likely affect cerebrospinal fluid fluxes and might underlie the enhancement of waste removal from the brain during sleep. The brain waste clearance was also found to be dependent on astrocytic water channels.
Overall, findings in this thesis paves the way for new studies that could potentially identify new treatment strategies for sleep disorders and neurodegenerative disorders.
Additional information
Contact the research support staff.