Objective
Cognitive deficits are common in most brain disorders and are characteristic of schizophrenia, which is among the most debilitating and costly diseases. Genetic association studies have implicated several potential schizophrenia-susceptibility genes, but a direct genetic cause/mechanism remains elusive. Schizophrenia is dependent upon dysregulation of the dopaminergic system, particularly in the prefrontal cortex (PFC). Catechol-O-methyltransferase (COMT) and dysbindin (dys) are two potential schizophrenia susceptibility genes which regulate cortical dopamine signaling and impact cognitive function. Schizophrenia is likely related to the combined malfunction of multiple genes rather than a single gene mutation. Genetic modifications resulting in selective reduction of either COMT or dys increase dopamine signaling in the PFC. Thus, we predicted that combined COMT*dys reduction in the same individual would demonstrate epistatic interaction between these genes through excessive cortical dopamine signaling. We are accumulating evidence in humans indicating that combined COMT and dys hypomorphisms is strongly associated with schizophrenic phenotypes and cognitive deficits. Therefore, we generated a COMT*dys double null mutant mouse (COMT*dys) which we propose to study for schizophrenia-like phenotypes. Because deficits in executive functions are at the core of schizophrenia, we aim to identify the specific cognitive domains affected by COMT*dys genetic interaction. Additionally, we shall investigate the neurophysiological correlates of such dysregulated behaviors in COMT*dys mice. In a therapeutic prospective, based on the recognized COMT/cannabinoids/schizophrenia interplay, we shall focus on the cross-talk between dopamine- and cannabinoid-mediated signaling in brain regions related to executive functions. This approach will shed light on specific genetic and cellular mechanisms contributing to psychiatric and cognitive abnormalities.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences neurobiology cognitive neuroscience
- medical and health sciences medical biotechnology genetic engineering
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine psychiatry schizophrenia
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-RG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
16163 Genova
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.