Preclinical molecular imaging to elucidate the role of the glutamatergic system in mood disorders

Abstract

Abnormal glutamate (Glu) neurotransmission has been implicated in the pathophysiology of multiple neuropsychiatric disorders. Modeling Glu disturbances allows for research to focus on the underlying molecular mechanisms, as well as to identify pharmacological targets. In obsessive-compulsive disorder (OCD), Glu modulation has come in the spotlight through studies suggesting that modulation of the N-methyl-D-aspartate (NMDA) receptor significantly reduces compulsive behavior. In schizophrenia, the Glu hypothesis suggests that NMDA receptor hypofunction disinhibits GABA-ergic inhibitory neurons that regulate glutamatergic neurons. Since NMDAR activity is largely refined by metabotropic glutamate receptors (mGluRs), research has shown that there is a role for mGluR5 dysregulation in schizophrenia. Huntington disease (HD) is characterized by progressive neuronal cell loss and studies have already suggested that positive allosteric modulators (PAMs) of mGluR5 affect memory and cognition positively. Based on this knowledge, there is a lot of incentive to be able to modulate Glu release, reuptake or binding. Either as a strategy to image target engagement or pathological consequences, or as a potential therapeutic strategy in itself.

Date of Award	2019
Original language	English
Awarding Institution	University of Antwerp
Supervisor	Ann Massie (Jury)