Tesis doctoral de Alejandro Amador Arjona
The overall goal of the neurobehavioural phenotyping of mouse models of disease group (genes and disease program, centre for genomic regulation) is to understand the role of candidate genes for human complex genetic diseases that could impair the structural elements with consequences on brain cognition systems. The aim of this thesis has been to elucidate the involvement of the neurotrophin-3 (nt-3) receptor, tropomyosin receptor kinase c (trkc), in human panic disorder (pd) pathophysiology. Previously, our laboratory demonstrated that transgenic mice overexpressing the ntrk3 gene encoding for trkc (tgntrk3) show phenotypic alterations similar to pd (dierssen et al, 2006). Briefly, validation of the model revealed that transgenic mice show anxiety/panic phenotypes, sensitivity to clinically effective pharmacological panicogenic and panicolitic agents, and mechanism homology with human pd. This has provided us with an excellent tool to investigate specific aspects of the pd pathophysiology. Concretely we have focused on the cognitive aspects underlying the panic attacks, namely emotional memories and sensory information processing, but also in stress susceptibility, as a triggering factor in the development of the altered fear memory in these patients. %&/Pd patients show an inability to correctly identify and possibly store fear-related information, which suggests alterations in brain regions that encode for the emotional properties of sensory stimuli and that interact with neural systems involved in attention, executive control and memory, key elements in the pathogenesis of pd. Moreover, pd patients experience anxiety and fear in response to an event/experience, which can be perceived as an external (real threat) or internal stressor that might be cause and/or consequence of a dysfunctional stress system. The main objective of this thesis has been the study of the potential involvement of trkc deregulation in fear memory, sensorimotor information processing and stress, using the pd model, tgntrk3. To this end, we have characterized behavioural, neuromorphological and neurohormonal aspects. Part of the work has been performed in the laboratory of professor martin keck (max planck institute, munich, germany) as a result of a short-stage fellowship.
Datos académicos de la tesis doctoral «Role of ntrk3 in the extinction of fear memories and in stress-coping: studies in a mouse model of panic disorder«
- Título de la tesis: Role of ntrk3 in the extinction of fear memories and in stress-coping: studies in a mouse model of panic disorder
- Autor: Alejandro Amador Arjona
- Universidad: Pompeu fabra
- Fecha de lectura de la tesis: 23/07/2008
Dirección y tribunal
- Director de la tesis
- Antonio Armario García
- Tribunal
- Presidente del tribunal: xavier Estivill pallej?
- monica Muñoz lópez (vocal)
- roser Nadal alemany (vocal)
- jordi Alberch i vie (vocal)