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AbstractAbstract
[en] Stress and its effect on the body remain an omnipresent topic in the field of health and social sciences. Despite the high interest a robust marker for the analysis of stress has yet not been identified. In this thesis a murine full-body analysis with 2-[18F]FDG µPET/µCT was used to establish suitable stress models for this method and evaluate whether it can be used as a robust marker for preclinical observation of the stress response in mice. Mice (C57BL/6) were stressed in three different ways: acute cooling, acute restrain and chronic cooling. Acute stress was conducted once for 1h in isolation (cooled or restraint) while chronic stress lasted over the course of 1 week. To observe the influence of obesity on stress response a high-fat diet obese mice model was also employed. Handling and imaging protocols were all optimized to improve the quality and reproducibility of results, since successful 2-[18F]FDG imaging is highly dependent on a multitude of factors such as consideration of circadian rhythm when monitoring stress (experiments from 8-12a.m.). Mice were anesthetized with Isoflurane for BGL and 2-[18F]FDG application as well as during the imaging procedure and scanned for 10min (static) or 70min (dynamic). Afterwards, serum samples were taken via cardiac puncture and animals sacrificed under anesthesia by cervical dislocation for subsequent dissection and harvesting of organs for ex-vivo biodistribution studies. Other methods were also used to gain further insight into the underlying mechanisms and additionally validate the newly established stress models. For this, corticosterone levels were quantified, as usually practiced, in serum samples via ELISA assay, but also in feces samples, representing a non-invasive less stress-inducing method. This work successfully showed the establishment of murine stress models including proper handling and imaging protocols, to be used for 2-[18F]FDG µPET/µCT analysis. Successful activation of stress response was identified by increased corticosterone levels via ELISA assay in serum and feces samples and activation of stress-related brain regions like hypothalamus, amygdala, and brain stem via 2-[18F]FDG µPET/µCT. Furthermore, we report for the first time that 2-[18F]FDG uptake in BAT is independent of the stress type or cold exposure and an increased uptake occurs in lean mice upon restrain. We were able to observe a number of trends in BAT uptake: a significantly reduced uptake in obese mice, no change in uptake upon stress in obese mice and a significantly higher BAT uptake in female mice. Obesity and sex also revealed to play a role in alteration of 2-[18F]FDG uptake in the heart. Lean mice do not show any significant changes in heart uptake after stress exposure whereas obese mice have a significantly increased uptake upon acute and chronic cooling. This trend is inverse to the changes in BAT uptake and suggests a difference in effects on target organs of the stress response, depending on the body type. All in all, 2-[18F]FDG-µPET/µCT imaging as conducted in this thesis proofed to be a suitable method for the evaluation of stress response activation and subsequent effects on the body. It was successfully used to observe changes depending on stress type, sex, and morphology. In the future it may be used to study stress and its outcome in multiple diseases and health conditions to gain further inside into this complex topic. (author)
Primary Subject
Source
2022; 95 p; Available from Vienna University, Library and archive services, Universitaetsring 1, 1010 Vienna (AT) and available from https://permalink.obvsg.at/AC16708658; Thesis (Ph.D.)
Record Type
Miscellaneous
Literature Type
Thesis/Dissertation
Country of publication
ADRENAL HORMONES, ANIMALS, BETA DECAY RADIOISOTOPES, BETA-PLUS DECAY RADIOISOTOPES, CORTICOSTEROIDS, DISEASES, FLUORINE ISOTOPES, GLUCOCORTICOIDS, HORMONES, HOURS LIVING RADIOISOTOPES, HYDROXY COMPOUNDS, ISOMERIC TRANSITION ISOTOPES, ISOTOPES, KETONES, LIGHT NUCLEI, MAMMALS, NANOSECONDS LIVING RADIOISOTOPES, NUCLEI, ODD-ODD NUCLEI, ORGANIC COMPOUNDS, PREGNANES, RADIOISOTOPES, RODENTS, STEROID HORMONES, STEROIDS, VERTEBRATES
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