D-Serine in Neuropsychiatric Disorders: New Advances

Abstract

D-Serine (DSR) is an endogenous amino acid involved in glia-synapse interactions that has unique neurotransmitter characteristics. DSR acts as obligatory coagonist at the glycine site associated with the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) and has a cardinal modulatory role in major NMDAR-dependent processes including NMDAR-mediated neurotransmission, neurotoxicity, synaptic plasticity, and cell migration. Since either over-or underfunction of NMDARs may be involved in the pathophysiology of neuropsychiatric disorders; the pharmacological manipulation of DSR signaling represents a major drug development target. A first generation of proof-of-concept animal and clinical studies suggest beneficial DSR effects in treatmentrefractory schizophrenia, movement, depression, and anxiety disorders and for the improvement of cognitive performance. A related developing pharmacological strategy is the indirect modification of DSR synaptic levels by use of compounds that alter the function of main enzymes responsible for DSR production and degradation. Accumulating data indicate that, during the next decade, we will witness important advances in the understanding of DSR role that will further contribute to elucidating the causes of neuropsychiatric disorders and will be instrumental in the development of innovative treatments.

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

“…Benzoic acid readily crosses the intestinal barrier and BBB to inhibit D-amino acid oxidase that catabolizes D-serine, a co-agonist of N-methyl-D-aspartate receptor (NMDAR, a type of Glu receptor) . Both D-serine and NMDARs are therapeutic targets in neuropsychiatric disorders, such as depression, schizophrenia and cognitive impairment (Durrant and Heresco-Levy, 2014). Indeed, a dysfunctional Glu system is linked to the pathophysiology of depression (Pytka et al, 2016).…”

An astroglial basis of major depressive disorder? An overview

“…d ‐serine controls neural development, synaptic transmission, plasticity and memory (Fossat et al, ; Sultan et al, ). Compared with the placebo, acute administration of d ‐serine to healthy subjects reduced the subjective feelings of depression and anxiety (Durrant and Heresco‐Levy, ). Moreover, the glycine‐transporter‐1 inhibitor sarcosine and the d ‐amino acid oxidase (the enzyme that degrades d ‐serine) inhibitor sodium benzoate are beneficial treatments for depressed patients who have been drug‐naive for at least 3 months and have no history of treatment resistance (Huang et al, ; Lai, Lane, & Tsai, ).…”

Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature

“…Several lines of evidence have shown that changes (e.g., availability, metabolism, and/or receptor activity) in neuroactive amino acids associated with central brain functions may play a role in the pathogenesis and/or pharmacotherapy of several psychiatric disorders (e.g., schizophrenia and mood disorders) that have symptoms, such as cognitive impairment and problems with social interactions, in common with ASD (Coyle 2006; Grant et al 2006; Lam et al 2006; Labrie et al 2008; Ongür et al 2008; Yüksel and Öngür 2010; Durrant and Heresco-Levy 2014). Several preclinical and clinical studies have implicated neuroactive amino acids in the etiology of ASD, fragile X syndrome, and tuberous sclerosis complex (TSC), but most of these studies have focused on glutamate, GABA, and/or glutamine (El-Ansary and Al-Ayadhi 2014; Rojas 2014; Santini et al 2014; Rozas et al 2015; Cochran et al 2015; Lozano et al 2015; Robertson et al 2016).…”