Objective
Understanding neural bases of stress, fear and anxiety is of an immense importance to modern society. Anxiety disorders affect about 25% of adults at least once in their lives, and make a huge social, family and welfare impact. The most dramatic form, post- traumatic stress disorder (PTSD) is characterized by cognitive impairment, depression, fear, anxiety and may eventually lead to suicide. Understanding of the neural mechanisms of PTSD and other anxiety disorders could reduce the personal and societal impact through development of more efficient therapies.
Fear memories are encoded as changes in strength of synaptic connections, a process called plasticity. Extra-cellular proteolysis provides an attractive mechanism underlying neuronal plasticity. Precisely orchestrated exocytosis of a protease could help remodel synaptic connections by degrading extra-cellular matrix proteins, interacting with membrane receptors or activating latent growth factors. Consistent with this idea we have recently shown that the tissue plasminogen activator (tPA)/plasmin system is regulated by restraint stress in the hippocampus and amygdala, and it promotes stress-related neuronal remodelling.
Moreover, our data indicate that other serine proteases are also key players in stress-induced plasticity and anxiety. The molecular mechanisms by which proteases facilitate stress-induced anxiety remain unclear. We propose to identify protease-regulated genes in the amygdala, and examine their roles during psychological stress using a combination of genetic, cell biological, pharmacological, electrophysiological and behavioural approaches.
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Call for proposal
FP6-2005-MOBILITY-8
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