Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Reichmann, F.
Impact of stress and colitis on neuronal plasticity in the amygdala-hippocampus network.
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medical University of Graz; 2014. pp. 144
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- Autor*innen der Med Uni Graz:
- Reichmann Florian
- Betreuer*innen:
- Holzer Peter
- Leitinger Gerd
- Altmetrics:
- Abstract:
- Background and Aim: Inflammatory bowel diseases (IBDs) are a major health concern, but the pathophysiology of these diseases is still incompletely understood. It was suggested that stress is a crucial factor in the development of IBDs, able to exacerbate disease course and to trigger flares. While a large body of evidence showed that stress negatively affects parameters of inflammation, the role of the gut-brain communication in this process remains largely elusive. Increasing evidence in animal experiments using environmental enrichment (EE), an alternative housing condition for mice, demonstrated that environmental factors may influence stress resilience, the ability to cope with stress. However, brain sites and molecular events producing this effect need further investigation. Whether EE influences the course of visceral inflammation is also unknown. In view of the complex interaction between stress and visceral inflammation, the current thesis project was designed to elucidate the role of psychological stress and particularly the brain response to stress in mouse models of chronic gastrointestinal inflammation. Methods: Gastrointestinal inflammation was modelled by dextran sulfate sodium-induced colitis and iodoacetamide-induced gastritis. Subgroups of animals were exposed to water avoidance stress (WAS), a psychological stress paradigm, and/or kept under EE. Readouts included neuronal activation in the brain, as measured by the quantification of the number of c-Fos- and FosB/¿FosB-expressing cells, brain neuropeptide Y (NPY) expression, structure and number of hippocampal synapses and various tests of emotional-affective behaviour. The efficacy of the treatments to induce visceral inflammation was assessed by colonic myeloperoxidase content and a disease activity score. Results: Several key findings arose from this project. 1) WAS produces strong neuronal activation in the brain. 2) WAS-induced neuronal activation is markedly blunted by gastrointestinal inflammation. 3) EE modifies WAS-induced neuronal activation of the hippocampus and the amygdala in an opposite manner. 4) EE-induced modifications of c-Fos levels are accompanied by an increase of hippocampal NPY expression and altered FosB/¿FosB levels, but not by a change of the hippocampal synaptic ultrastructure. 5) EE increases the susceptibility to colitis and alters stress-induced neuronal activation in the brain under inflammatory conditions. 6) WAS, but not colitis, influences emotional-affective behaviour. 7) WAS and colitis differentially modify NPY expression within the hippocampus, amygdala and hypothalamus. Conclusions: My data contribute to the growing literature that the brain is an important factor in the course of visceral inflammation. The molecular changes observed in the brain indicate that altered gut-brain signalling in response to gastrointestinal inflammation can impair brain function. In a translational view, these data add further information on how stress can negatively affect the course of IBD. Especially the alterations observed in the limbic system provide an additional explanation why emotional processing is impaired in IBD. Furthermore, these data expand the knowledge as to how EE reduces negative consequences of stress exposure. In line with the current literature, the hippocampus was identified as the structure showing the most pronounced EE effects. Particularly the finding of increased hippocampal NPY expression points to a signal pathway whereby EE confers stress resilience. Surprisingly, EE increased the susceptibility to colitis, which is in contrast to positive effects of EE in other disease models. This effect may be explained by the immunomodulatory properties of EE, but needs further investigation.