Inhaltszusammenfassung

Biological homeostasis is a dynamic equilibrium in which internal physiological parameters, such as pH, osmotic pressure or temperature, are actively kept within a specific range in the organism. The homeostatic range is not fixed and may change throughout the lifespan of an individual. However, the homeostatic state can also be transiently modified in the presence of internal or external perturbations. The aim of this new homeostasis, or also called allostatic state, is to facilitate the ada...Biological homeostasis is a dynamic equilibrium in which internal physiological parameters, such as pH, osmotic pressure or temperature, are actively kept within a specific range in the organism. The homeostatic range is not fixed and may change throughout the lifespan of an individual. However, the homeostatic state can also be transiently modified in the presence of internal or external perturbations. The aim of this new homeostasis, or also called allostatic state, is to facilitate the adaptability of the organism. Brain homeostasis should ensure the optimal conditions for an efficient and correct flow of information within the nervous system and, as a consequence, the survival of the individual. However, neurons are very sensitive cells that require a tight control of their neuronal activity to avoid cellular damage and maladaptive responses. The endocannabinoid system (ECS) is a major neuromodulatory signaling system and has fundamental roles in restoring neuronal homeostasis once the neural signal has been transmitted. Furthermore, the high and widespread abundance of the ECS across different brain regions and cell populations suggests its relevance for the optimal functioning of the brain as a whole. One of the aims of this thesis was to characterize the hippocampal transcriptome of mice lacking the cannabinoid type 1 receptor (CB1), the main receptor of the ECS, in either glutamatergic or GABAergic neurons. The consequence of these genetic manipulations is an excess of excitatory and inhibitory neurotransmission at the synapses, respectively. Under basal, non-stressed conditions, these mutant mice are very similar in their behavioral phenotype as compared to their wild-type controls, yet their neuronal morphology is strongly altered. However, upon external challenges, the transcriptome was observed to react very differently in each conditional CB1 mutants and, partly, even in a dichotomic manner. These observations suggest that the brains of these two conditional CB1 mutants have adopted different allostatic states in response to an excess of excitation and inhibition, respectively, as compared to the wild-type control mice. Understanding how to reach and modulate these allostatic states could be relevant for specific pathologies, such as epilepsy or stress-related disorders. There is a plethora of factors that influences brain homeostasis, such as developmental stage, past experiences and genetics. As a consequence thereof, two individuals cannot have an identical brain homeostasis, which has important implications in psychiatric disorders, such as depression and stress-related pathologies. We hypothesize that the wide dispersion of behavioral responses observed in populations exposed to the same stressor or traumatic experience is a result of differences in the individual’s brain homeostasis. Thus, these differences would translate in different stress coping abilities, with individuals classified as either resilient, when they can successfully deal with the stressor, or susceptible, when they develop serious disorders. In this context, we developed a single-trauma stress model to induce posttraumatic stress disorder (PTSD)-like behaviors in mice. Our first aim was to study the behavior of trauma-exposed mice and determine which of them showed a resilient or susceptible phenotype, using for this purpose a set of pre-defined features based on the diagnostic criteria of human PTSD patients. Our final goal was to characterize different brain regions from the resulting phenotypes at different molecular levels and search for putative mechanisms that could explain the behavioral differences. This approach is proposed to improve the segregation of trauma-exposed mice into the resilient and susceptible phenotypes and, thus, should help to understand the underlying neurobiological mechanisms.» weiterlesen» einklappen

Autoren

Klassifikation

DDC Sachgruppe:
Biowissenschaften, Biologie