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
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture - time and place
Adjudication committee
- First opponent: Dr. Peter Bedner, University of Bonn, Germany
- Second opponent: Professor Maja Jagodic, Karolinska Institutet, Stockholm, Sweden
- Third member and chair of the evaluation committee: Professor II Bjørnar Hassel, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor II Espen Dietrichs, Institute of Clinical Medicine, University of Oslo
Principal supervisor
Post doc Kjell Heuser, Oslo University Hospital
Summary
Epileptogenesis, the metamorphosis of a physiological into an epileptic brain, is characterized by gradual cellular alterations like neuronal death, reactive (astro-) gliosis and neuroinflammation.
Upstream mechanisms for these changes remain elusive and in lack of adequate targets, the last decades of epilepsy drug development have failed to improve treatment.
This thesis sheds light on potential upstream mechanisms by:
A) analyzing DNA methylation (RRBS) and gene expression (RNA sequencing) in neurons and glia cells separately.
B) assessing the seizure phenotype (EEG) and morphological changes (immunohistochemistry) in mice with dysfunctional astrocytes
Results from A) represent the first of their kind in epilepsy research. A cell specific analysis of DNA methylation and gene expression allows to determine the cellular origin of the observed alterations. The results revealed a crucial involvement of glia cells in an early phase of epileptogenesis; glia cells contributed to both neuronal death, neurogenesis, blood-brain barrier dysfunction and inflammatory pathways. Further, our results showed overlap in gene expression with other neurodegenerative conditions like Parkinsons disease, multiple sclerosis and Alzheimers. Seizures alone induce many epileptogenesis relevant genes but may not suffice to induce epileptogenesis. Our results further indicate that DNA methylation may not play the anticipated role in gene expression regulation at an early time point of epileptogenesis.
Data from B) indicates that dysfunctional astrocytes lead to aggravated epileptogenesis. Mice with astrocytes depleted of IP3R2 (with consecutive impairment of calcium signaling in astrocytes) died due to epileptic activity, experience more epileptic seizures and potentially also a higher ratio of neuronal death and reactive gliosis.
Taken together, this work has contributed to a better understanding of epileptogenesis by shedding light on molecular mechanisms in neurons / glia and investigating the role of (dys-)functional astrocytes in epileptogenesis.
The gained knowledge may serve the development of truly anti-epileptogenic drugs.
Additional information
contact the research support staff