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Cannabinoid receptors CB1 in schizophrenia: role of brain mitochondrial activity and astroglial signalling (SCHIZO-mtCB1)
Start date: Feb 1, 2015, End date: Jan 31, 2017 PROJECT  FINISHED 

"Schizophrenia is a severe psychiatric disorder characterized by a series of ""positive"" and ""negative"" symptoms, which eventually lead to strong sufferance, social isolation and occupational impairment. Via activation of type-1 cannabinoid receptors (CB1), cannabinoids are known to induce schizophrenic-like symptoms, which are major caveats in the possible therapeutic use of these compounds. On the other hand, mitochondria-dependent regulation of brain bioenergetics is emerging as a promising novel research path in the field of psychopathology of schizophrenia. Previous results suggest the implication of mitochondrial (mtCB1) and astrocytic-CB1 receptors in psychotic-like conditions. However the precise molecular and cellular links between ECS activity and schizophrenia are not known. The aim of this study is to test whether mithocondrial and/or astrocytic CB1 receptors represent a functional link between endocannabinoid signalling in the brain and psychotic-like behaviours. (1) Firstly, the project will be dedicated to the generation of specific genetic tools to clearly discriminate mtCB1 from other CB1 receptor locations in the cell. (2) Then, these specific tools and specific transgenic mice will be used to investigate the role of mtCB1 and astrocytic-CB1 receptor in ""psychosis-like"" effects of cannabinoid drugs, and (3) to study the role of these receptors in a schizophrenia-like mouse model. This project will improve our understanding of the pathophysiology of psychotic-like disorders and might pave the way to novel therapeutic opportunities to improve the life of patients."
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