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AGLAEA — Result In Brief

Project ID: 37554
Country: France

Models for glutamate-related disorders

Studying the molecular basis of any disease requires the appropriate in vitro and in vivo models. To investigate the role of the neurotransmitter glutamate in various central nervous system (CNS) disorders, European scientists developed novel animal models.
Models for glutamate-related disorders
Altered glutamate transmission is involved in numerous psychiatric diseases including schizophrenia, anxiety and cognitive disorders. However, very few pre-clinical models are available in order to study the effects of glutamate on the onset and development of such diseases, and to test new therapeutic drugs.

Seeking to address this issue, the EU project Aglaea focused on developing in vivo models of selective, partial knockdown of specific components of the brain glutamatergic system. More specifically, project partners chose to silence the expression of the glutamate membrane transporter (EAAT2 / GLT-1) and the vesicular membrane transporter (VGLUT1), two proteins that are involved in maintenance and release of glutamate, respectively.

Selective protein knockdown was achieved through administration of small interfering RNAs (siRNA) directly into the brain ventricles of the animal. Behavioural analysis indicated that disruption of GLT1 transporter induced an anxiogenic behaviour, while knockdown of VGLUT1 impaired specific aspects of cognition.

Scientists also used these models to test various drugs and antagonistic compounds that could reverse the observed phenotypes. Results demonstrated the potential of these pre-clinical models for assessing the therapeutic value of novel compounds.

The Aglaea project findings provided invaluable insight into the role of glutamate in cognitive behaviour. Furthermore, the pre-clinical models will pave the way for the generation of transgenic animals to study the neurobiological and neurochemical bases of various psychiatric disorders.

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