AGLAEA PROJECT : USEAGE OF IN VIVO SHRNA AND TRANSGENIC APPROACHES

Glutamate is the most abundant excitatory transmitter in the brain. However, few animal models exist to explore the potential of drugs that modulate glutamate transmission.

Altered glutamate transmission is involved in numerous psychiatric diseases resulting in the need for models to characterise the effects of hypo- and hyper-glutamatergic states involved in the onset and development of psychiatric diseases.

AGLAEA will develop and characterise models of selective, partial knockdown of specific components of the brain glutamatergic system in mice. These models 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 improved testing of new drugs for treatment. In order to selectively turn off specific components of the glutamatergic pathways, both siRNA and shRNA approaches will be used. The effect of altered glutamate signalling will be characterised using functional MRI (fMRI) and microdialysis/microsensormethodology. Specific behavioural tests will be used to assess the functional effects of disordered glutamate transmission relevant to specific psychiatric diseases. Furthermore, the data collected from siRNA and shRNA experiments will be applied to the generation of transgenic mice, in which modulation of glutamate signaling will be induced at different stages of development.

SEE THE RESULTS : http://www.aglaea.com/fileadmin/user/pdf/Aglaea_brochure.pdf

Kraje

France