2024-03-29T09:44:13Zhttps://www.tdx.cat/oai/requestoai:www.tdx.cat:10803/71262024-03-15T10:57:35Zcom_10803_236col_10803_690278
00925njm 22002777a 4500
dc
Amador Arjona, Alejandro
author
2008-07-23
The correct development and function of CNS is critical for brain health of the organism. Early or chronic stress causes prominent alterations in brain function, and affects the expression of neurotrophic factors in limbic brain regions involved in the regulation of mood and cognition. Recent evidences have opened the idea that in complex organisms, an altered expression of certain neurotrophins by stress could be involved in the onset and pathophysiology of most psychiatric disorders, such as depression, squizophrenia or anxiety disorders. It is hypothesized that altered levels of neurotrophic factors could contribute to the atrophy and cell death of these regions, including the hippocampus and prefrontal cortex, which would produce a malfunction in limbic-related areas, and as a consequence, a precipitation or worsening of psychiatric illnesses. We were interested in panic disorder pathophysiology, which is a stress-related disorder and is characterized by an altered cognitive processing of emotional information. Although little evidence has been found supporting a neurotrophic role in PD, recent data has revealed that NT-3/TrkC signaling might play a key role in limbic system morphology and function. Therefore, we suggest that NT-3/TrkC system is involved in PD pathogenesis. <br/><br/>The main objective in the work of this doctoral thesis lie to determine the role of NTRK3 gene, that codifies for TrKC, in emotional cognition and stress response processes that underlies PD. To this end, we used a genetically modified mouse model of NTRK3 overexpression, which was validated as a model of PD. Here, it is characterized the effects produced by the increase of NTRK3 expression in the CNS, focusing in neural alterations that might influence changes in cognitive processes involved in coping strategies. Moreover, it is studied the mechanisms that underlie in these processes by different approaches, 1/physiologically, measuring the HPA axis response, 2/brain activation, analyzing the activation pattern to a stress stimulus, 3/cellular and gene expression profiling, characterizing key brain regions in cognitive processes, and 4/pharmacologically, studying neurotransmitters function.
9788469234594
http://www.tdx.cat/TDX-0519109-103054
http://hdl.handle.net/10803/7126
B.25460-2009
amygdala
stress sensitization
hippocampus
prepulse inhibition
fear memory
stress
locus coeruleus
anxiety-like behaviour
TrkC
NT-3
Panic disorder
Role of NTRK3 in the extinction of fear memories and streess-coping: studies in a mouse model of panic disorder