The role of D-Serine in the cellular communication between neurons and astrocytes during neurodevelopment

Abstract

Schizophrenia is an incurable mental disorder that affects 1% of the world population and is among the most disabling human diseases. On average, 70% of patients abandon medication due to its low efficacy and the presence of severe side effects. To change these conditions, it is necessary to understand the pathophysiology of schizophrenia at the molecular level. Besides the long-established neurodevelopmental hypothesis, works based on neuroimaging, postmortem brain proteomics, and pharmacological, genetic, and animal model studies have shown dysfunction in glial cells and deficits in synaptic transmission. As all these factors may be connected in the development of this complex disorder, we intend to integrate neuroproteomics, pluripotent stem cells, and CRISPR-CAS9 to further investigate the biological mechanisms involved in synaptic dysfunction, since the early neurodevelopment. To achieve this, we propose to study the role of D-Serine formation in astrocyte-neuron communication in a neurodevelopmental model. We intend to unravel how deregulation of this communication may influence on the formation of neural connections and signaling pathways, which are defective in diseased brains.