PMID- 37833512 OWN - NLM STAT- MEDLINE DCOM- 20231204 LR - 20231221 IS - 1438-2199 (Electronic) IS - 0939-4451 (Print) IS - 0939-4451 (Linking) VI - 55 IP - 11 DP - 2023 Nov TI - Cross species review of the physiological role of D-serine in translationally relevant behaviors. PG - 1501-1517 LID - 10.1007/s00726-023-03338-6 [doi] AB - Bridging the gap between preclinical models of neurological and psychiatric disorders with their human manifestations is necessary to understand their underlying mechanisms, identify biomarkers, and develop novel therapeutics. Cognitive and social impairments underlie multiple neuropsychiatric and neurological disorders and are often comorbid with sleep disturbances, which can exacerbate poor outcomes. Importantly, many symptoms are conserved between vertebrates and invertebrates, although they may have subtle differences. Therefore, it is essential to determine the molecular mechanisms underlying these behaviors across different species and their translatability to humans. Genome-wide association studies have indicated an association between glutamatergic gene variants and both the risk and frequency of psychiatric disorders such as schizophrenia, bipolar disorder, and autism spectrum disorder. For example, changes in glutamatergic neurotransmission, such as glutamate receptor subtype N-methyl-D-aspartate receptor (NMDAR) hypofunction, have been shown to contribute to the pathophysiology of schizophrenia. Furthermore, in neurological disorders, such as traumatic brain injury and Alzheimer's disease, hyperactivation of NMDARs leads to synaptic damage. In addition to glutamate binding, NMDARs require the binding of a co-agonist D-serine or glycine to the GluN1 subunit to open. D-serine, which is racemized from L-serine by the neuronal enzyme serine racemase (SRR), and both SRR and D-serine are enriched in cortico-limbic brain regions. D-serine is critical for complex behaviors, such as cognition and social behavior, where dysregulation of its synthesis and release has been implicated in many pathological conditions. In this review, we explore the role of D-serine in behaviors that are translationally relevant to multiple psychiatric and neurological disorders in different models across species. CI - (c) 2023. The Author(s). FAU - Arizanovska, Dena AU - Arizanovska D AD - The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Emodogo, Jada A AU - Emodogo JA AD - Translational Psychiatry Laboratory, McLean Hospital, Belmont, MA, USA. FAU - Lally, Anna P AU - Lally AP AD - Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA, USA. FAU - Palavicino-Maggio, Caroline B AU - Palavicino-Maggio CB AD - Department of Psychiatry, Harvard Medical School, Boston, MA, USA. AD - Neurobiological Mechanisms of Aggression Laboratory, McLean Hospital, Belmont, MA, USA. FAU - Liebl, Daniel J AU - Liebl DJ AD - The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Folorunso, Oluwarotimi O AU - Folorunso OO AD - Department of Psychiatry, Harvard Medical School, Boston, MA, USA. ofolorunso@mclean.harvard.edu. AD - Translational Psychiatry Laboratory, McLean Hospital, Belmont, MA, USA. ofolorunso@mclean.harvard.edu. LA - eng GR - P50 MH115874/MH/NIMH NIH HHS/United States GR - R00 GM141449/GM/NIGMS NIH HHS/United States GR - T32 MH125786/MH/NIMH NIH HHS/United States GR - T32MH125786/MH/NIMH NIH HHS/United States PT - Journal Article PT - Review DEP - 20231013 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 452VLY9402 (Serine) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - EC 5.1.- (Racemases and Epimerases) SB - IM MH - Animals MH - Humans MH - Serine/metabolism MH - Genome-Wide Association Study MH - *Autism Spectrum Disorder MH - Neurons/metabolism MH - Receptors, N-Methyl-D-Aspartate/genetics/metabolism MH - *Nervous System Diseases MH - Racemases and Epimerases PMC - PMC10689556 OTO - NOTNLM OT - Cognition OT - D-Serine OT - Serine racemase OT - Sleep OT - Sociability COIS- All authors have nothing to disclose. EDAT- 2023/10/14 10:43 MHDA- 2023/12/04 12:43 PMCR- 2023/10/13 CRDT- 2023/10/13 23:46 PHST- 2023/06/01 00:00 [received] PHST- 2023/09/19 00:00 [accepted] PHST- 2023/12/04 12:43 [medline] PHST- 2023/10/14 10:43 [pubmed] PHST- 2023/10/13 23:46 [entrez] PHST- 2023/10/13 00:00 [pmc-release] AID - 10.1007/s00726-023-03338-6 [pii] AID - 3338 [pii] AID - 10.1007/s00726-023-03338-6 [doi] PST - ppublish SO - Amino Acids. 2023 Nov;55(11):1501-1517. doi: 10.1007/s00726-023-03338-6. Epub 2023 Oct 13.