Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction: Schizophrenia is characterized by reduced hippocampal volume, decreased dendritic spine density, altered neuroplasticity signaling pathways, and cognitive deficits associated with impaired hippocampal function. We sought to determine whether this diverse pathology could be linked to NMDA receptor (NMDAR) hypofunction, and thus used the serine racemase-null mutant mouse (SR-/-), which has less than 10% of normal brain d-serine, an NMDAR coagonist. We found that d-serine was necessary for the maintenance of long-term potentiation in the adult hippocampal dentate gyrus and for full NMDAR activity on granule cells. SR-/- mice had reduced dendritic spines and hippocampal volume. These morphological changes were paralleled by diminished BDNF/Akt/mammalian target of rapamycin (mTOR) signaling and impaired performance on a trace-conditioning memory task. Chronic d-serine treatment normalized the electrophysiological, neurochemical, and cognitive deficits in SR-/- mice. These results demonstrate that NMDAR hypofunction can reproduce the numerous hippocampal deficits associated with schizophrenia, which can be reversed by chronic peripheral d-serine treatment.
In 2013 the initiative “International Working Group on Neurotransmitter Related Disorders (iNTD)” was founded. The major goal of Network I is to set-up a web-based patient registry for inherited defects of biogenic amines, pterin, folate, serine, glycine and GABA metabolism. It includes 42 scientific and clinical partners from 26 countries. This aims
D-Serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor: Functional activity of N-methyl-d-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although d-serine is a more potent agonist. Localizations of d-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine. We now show that selective degradation of d-serine with d-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux. The inhibitory effects of the enzyme are fully reversed by exogenously applied d-serine, which by itself did not potentiate NMDA receptor-mediated synaptic responses. Thus, d-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses.
My botty best at summarizing from Wikipedia: Serine (symbol Ser or S) is an -amino acid that is used in the biosynthesis of proteins . it can be synthesized in the human body under normal physiological circumstances . only the serine was first obtained from silk protein, a particularly rich source, in 1865 by Emil Cramer . it is synthesized in the body from other metabolites, including glycine . serine is catalyzes reversible conversions of L-serine to glycine (retro-aldol cleavage) SHMT is a pyridoxal phosphate ( nerve gases and substances used in insecticides inhibit enzyme completely . side chain can undergo O-linked glycosylation, which may be related to diabetes . one of three amino acid residues commonly phosphorylated by kin serine proteases are a common type of protease . D-serine is a potent agonist at the glycine site (NR1) of the NMDA-type glutamate pure D-serine is an off-white crystalline powder with a faint musty aroma . it plays a signaling role in peripheral tissues and organs such as cartilage, kidney and corpus cavernosum D-Serine is sweet with an additional minor sour taste at medium and high concentrations . at present three disorders have been reported: 3-phosphoglycerate dehydrogenase deficiency, 3- a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD) a 2011 meta-analysis found adjunctive sarcosine to have a medium effect size for
