AGLAEA - DEVELOPMENT OF NOVEL ANIMAL MODELS OF GLUTAMATERGIC CENTRAL NERVOUS SYSTEM DISORDERS USING IN VIVO SIRNA AND TRANSGENIC APPROACHES (FP6-LIFESCIHEALTH) (2007-01-01 - 2009-12-31) (»add to infobox)

Mark EPPING-JORDAN, Andras DINNYES, Raffaella CATENA, Thomas CREMERS, Bernard H. C. WESTERINK, Charles MARSDEN

ADDEX PHARMACEUTICALS FRANCE SAS (FR718 - Haute-Savoie) (France), MEZOGAZDASAGI BIOTECHNOLOGIAI KUTATOKOZPONT (HU102 - Pest) (Hungary), ALMA CONSULTING GROUP SAS (FR716 - Rhône) (France), BRAINS ONLINE BV (NL113 - Overig Groningen) (Netherlands), RIJKSUNIVERSITEIT GRONINGEN (NL113 - Overig Groningen) (Netherlands), THE UNIVERSITY OF NOTTINGHAM (UKF14 - Nottingham) (Great Britain)

Glutamate is the most abundant excitatory transmitter in the brain. However, very few models exist to explore the potential of drugs that modulate glutamate transmission. Because altered glutamate transmission is involved in numerous psychiatric diseases, there is a strong need for such models, to characterise the effects of hypo- and hyper-glutamatergic states on the onset and development of such diseases. AGLAEA will develop and characterise models of selective, partial knockdown of specific components of the brain glutamatergic system in mice. This will provide better comprehension of the implication of glutamate signalling in diseases such as schizophrenia, anxiety and cognitive disorders. AGLAEA will lead to breakthrough research on the neurobiological and neurochemical bases of psychiatric disorders and will enable the further testing of new drugs for treatment. In order to selectively turn off specific components of the glutamatergic pathways, an siRNA approach will be used. The effect of modulation of glutamate signalling will be characterised using functional MRI (fMRI) and microdialysis/microsensor analysis. Specific behavioural tests will be carried out on live animals for the assessment of glutamate-related psychiatric disorders. Furthermore, the data collected from siRNA experiments will be applied to the generation of transgenic mice, in which modulation of glutamate signaling will be induced at different stages of development. Therefore, AGLAEA will provide both the pharmaceutical and the academic world with potent models. These models will be used to test novel compounds and assess their therapeutic value and will benefit researchers investigating the neurobiological and neurochemical bases of those diseases. The consortium set up to reach the objectives of AGLAEA gathers 3 high tech SMEs, 2 academic groups and one large group for the management of the project (ALMA), representing all together 4 European countries (FR, HU, UK, NL).

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