Neuropharmacology

Biography

Biography: Gerson Duarte Guercio

Abstract

D-serine is an endogenous co-agonist of NMDA receptor, which plays a crucial role in many aspects of cognition. Animal research suggested that the co-agonist site was not saturated, and subsequent studies demonstrated that d-serine administration improved rodent’s performance in many memory tasks. Recently, D-serine pro-cognitive effects were observed even in healthy adults and in the elderly. In addition, given the important role of D-serine in cognition, there was growing interest to find out whether its pathway was affected in psychiatric disorders. So far, D-serine has mostly been implicated in the etiology of schizophrenia. For instance, animal models with decreased D-serine levels recapitulated many endophenotypes of the disorder. Lower D-serine levels have been found in cerebrospinal fluid and in the blood of patients with schizophrenia, and evidence indicates a higher activity of the enzyme responsible for metabolizing D-serine, D-amino acid oxidase, in post-mortem brains of the patients. In intervention studies, D-serine added to antipsychotics had a moderate effect in treating the cognitive deficits and negative symptoms. In sum, D-serine has a great potential as a cognitive enhancer in healthy adults and in patients with schizophrenia. However, I’ll address many questions that need to be solved, regarding D-serine pharmacokinetics, possible side-effects, other strategies to increase its levels and combination with other therapies to increase efficacy.