Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Juan P. Bolanõs, University of Salamanca, Spain
- Second opponent: Assistant professor Evita Wiegers, University Medical Center Utrecht, The Netherlands
- Third member and chair of the evaluation committee: Professor Rune Enger, University of Oslo
Chair of the Defence
Professor Stine Marie Ulven, University of Oslo
Principal Supervisor
Professor Johanne Egge Rinholm, University of Oslo
Summary
This doctoral thesis explores novel roles of lactate and the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1) in the brain, moving beyond the traditional view of lactate as a mere byproduct of anaerobic metabolism.
The thesis examines how lactate signaling through HCAR1 influences brain development, injury response, and plasticity. Emphasis is placed on neonatal cerebral conditions, including hypoxic–ischemic brain injury and hypoglycemia, as well as on adaptations induced by high-intensity physical exercise. The work addresses how lactate-dependent signaling affects neuronal and glial cell behavior, immune responses, axonal development, and vascular remodeling in the brain.
A combination of experimental models was used, primarily in mice, including in vivo models of neonatal brain injury and ex vivo organotypic brain slice cultures for neonatal hypoglycemia. Analyses of brain tissue, cell cultures, and gene expression were performed using established histological, imaging, and molecular techniques.
The findings suggest that HCAR1 is involved in long-term preservation of brain tissue following neonatal hypoxic–ischemic injury and is linked to widespread gene expression changes, particularly affecting pathways related to cell cycle regulation and innate immunity. Lactate was also observed to exert protective effects on axonal and myelin development under hypoglycemic conditions, where HCAR1 appeared to play a contributory role. Furthermore, repeated high-intensity exercise in mice led to an increase in cerebral capillary density, an effect that was dependent on intact HCAR1 signaling. Together, these results indicate that lactate signaling may play an important role in both normal brain physiology and neonatal cerebral pathology.
Additional information
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