Friday 3 November 2017, at 13:00, The Technical University of Denmark, Anker Engelunds Vej, Building 101A, Room S09.
Summary:
Over the last three decades, mean body-mass index (BMI) has increased steadily worldwide, and in the US the prevalence of obesity was 35.5% among adult men and 35.8% among adult women in 2009-2010. The high prevalence of obesity has intensified interest in obesity as a major health problem due to associated comorbidities.
The brain is heavily involved in appetite regulation and body weight control and is thus an important organ to study in order to develop improved treatment options for obesity. As brain access of pharmaceutical compounds is restricted by the blood brain barrier a better understanding on how and where pharmaceutical compounds enter the brain is needed.
The aim of the PhD project was to develop algorithms to enable automated quantification of preclinical Light Sheet Fluorescence Microscopy images. This was accomplished by utilization of image registration to integrate the microscopy data with a digital brain atlas from the Allen Institute of Brain Science. The developed methodology enabled high throughput analysis of acquired microscopy data regarding brain access, brain receptor mapping, and brain activity.
The developed analysis tools were used to study glucagon-like peptide 1 receptor agonists (GLP-1RAs) which are a class of peptide hormones previously shown to affect appetite regulation. During the PhD work it was showed that subcutaneously administrated GLP-1RAs were able to access the brain and lead to activation in brain regions related to decreased food intake.
Integration and analysis of data acquired during the PhD project together with data from future experiments will potentially help to discover new knowledge otherwise hidden in the large complexity of the brain and thereby possibly aid in development of improved treatment options for people with obesity.
Read more about this thesis in DTU Orbit.
Principal Supervisor: Associate Professor Anders Bjorholm Dahl, DTU Compute
Co-supervisor: Professor emeritus Knut Conradsen, DTU Compute
Co-supervisor: Anna Secher, Novo Nordisk
Co-supervisor: Jacob Hecksher-Sørensen, Novo Nordisk
Examiners:
Associate Professor Tim Bjørn Dyrby, DTU Compute
Professor Mads Nielsen, University of Copenhagen.
Professor Deniz Kirik, Lund University, Sweden
Chairman at defence:
Associate Professor Allan Aasbjerg Nielsen.