Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Tim Emmerzaal (Donders series 552)

22 March 2022

Promotor: prof. dr. L.T. Kozicz
Co-promotor: dr. R.J.T. Rodenburg

Mitochondria, stress, and the brain; Their interactions in mouse models for stress-related psychopathologies

Mitochondria are mainly known for their energy production capacity and are present in almost all cells of the body. Besides this essential function, it is also increasingly acknowledged that mitochondria play essential roles in other processes such as reactive oxygen species production, apoptosis, calcium signalling and homeostasis, steroid synthesis, and heat generation. More recently, mitochondrial bioenergetics is also increasingly associated with several stress-related neuropsychiatric disorders, including major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and anxiety disorders. Although a relatively large body of literature has been generated on the involvement of mitochondria in several psychopathologies, the exact mechanisms explaining the aetiology of psychopathologies is still largely elusive. The various studies described in this thesis aimed to examine several aspects of mitochondrial function and stress-associated mental disorders such as PTSD and MDD in several animal models. We did so by employing several different preclinical animal models for MDD and PTSD and different measurement techniques in various tissues and samples. In general, the results of this thesis confirm and elaborate on the findings that severe and chronic stress can influence mitochondrial functioning and its downstream effects both in the periphery as well as the brain. In addition to this, by using a novel mouse model with suboptimal mitochondrial function we showed that mitochondria influence the stress response in these mice. It also became clear that there are brain-region specific effects regarding mitochondrial functioning, which will be important in future studies as antidepressants can differentially affect mitochondrial function in these different brain regions. Therefore, considering the unique bioenergetic characteristics of an individual with a psychological disease could lead to personalized antidepressant treatment suited to their underlying mitochondrial bioenergetic capacity, in a more personalized medicine approach.