La plasticité de la transmission glutamatergique : implications pour les troubles psychiatriques

 

Tak Pan Wong

Institut universitaire en santé mentale Douglas

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme chercheurs-boursiers - Senior

Concours 2015-2016

More than 12% of the world population currently suffers from psychiatric disorders (WHO), which comprise of a wide range of diseases (e.g. depression, schizophrenia, and dementia) that exhibit abnormality with thoughts, moods and behaviors. Recent findings suggest that many symptoms of psychiatric disorders are related to changes in glutamatergic transmission, a neurochemical system that mediates excitation of brain cells. Indeed, changes in the levels of glutamate or the density of glutamate receptors have been revealed in brain tissue from patients of psychiatric disorders. Drugs targeting the glutamatergic system have also been shown to have antidepressant and antipsychotic effects. Findings from these human studies are bases of emerging basic neuroscience research that using animal models to investigate molecular mechanisms underlying the contribution of glutamatergic transmission to psychiatric disorders.

We have developed a research program using multidisciplinary approaches to examine changes in the functional properties of glutamatergic transmission in animal models of psychiatric disorders. These models are mouse or rats expressing symptoms that are related to psychiatric disorders such as depression, schizophrenia or Alzheimer's disease. Our research program has three objectives. Firstly, we examine the role of a type of glutamate receptors namely NMDA receptors in depression-related behaviors. Secondly, we investigate whether changes in glutamate receptor function caused by infection during pregnancy increase the risk of schizophrenia. Thirdly, we determine whether rescuing changes in glutamatergic transmission prevents the development of neurodegeneration in an animal model of Alzheimer's disease.

Findings from these studies not only could reveal molecular mechanisms underlie changes in glutamatergic transmission in these animals, but also could be developed into novel therapeutic targets for treating related psychiatric disorders.