Development of Novel Animal Models of Glutamatergic Central Nervous System Disorders Using in vivo siRNA and Transgenic Approaches
EU FP6 Specific Targeted Research Project-SME
Participant's number: 6
Role: Scientific partner

Objectives: 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 is working on the development and characterization of mouse-models with selective, partial knockdown of specific components in the brain glutamatergic system. This will provide better comprehension of the implication of glutamate signalling in diseases such as schizophrenia, anxiety and cognitive disorders. In order to selectively turn off specific components of the glutamatergic pathways, an siRNA approach is used. The effect of modulation of glutamate signalling can be characterised using functional MRI (fMRI) and microdialysis/microsensor analysis. Specific behavioural tests are carried out on live animals for the assessment of glutamate-related psychiatric disorders. The data collected from siRNA experiments are applied to the generation of transgenic mice, in which modulation of glutamate signaling will be induced at different stages of development. 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, representing all together 4 European countries (FR, HU, UK, NL).

Supervisor: Dr. Anita Fehér