Analysis of free d-serine in mammals and its biological relevance

Nishikawa, Toru

doi:10.1016/j.jchromb.2011.08.030

Cited by 131 publications

(87 citation statements)

References 177 publications

(359 reference statements)

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“…In the mammalian central nervous system, the probable physiological substrate for DAO is DSer, which has been proposed to be a neuromodulator that binds to the NMDA receptor as a coagonist and potentiates glutamatergic neurotransmission (51,60,68). Among the NMDA receptor subunits identified in mammals, NR1 and NR2A are conserved in C. elegans (NMR-1 and NMR-2, respectively), and these C. elegans orthologues are expressed exclusively in the command interneurons (9,32).…”

Section: Discussionmentioning

confidence: 99%

“…It is also present in the mammalian forebrain, where it persists at high concentrations throughout the life of the animal. DSer is now considered a neuromodulator that binds to the glycinebinding site of the N-methyl-D-Asp (NMDA) receptor, a subtype of the L-glutamate (L-Glu) receptor, and potentiates glutamatergic neurotransmission in the central nervous system (51,60,68). In fact, astroglia-derived D-Ser has been shown to regulate NMDA receptor-dependent long-term potentiation and/or long-term depression, which are basic processes of learning and memory, in the hypothalamic and hippocampal excitatory synapses (25,54).…”

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confidence: 99%

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Spatiotemporal Localization of d-Amino Acid Oxidase and d-Aspartate Oxidases during Development in Caenorhabditis elegans

Saitoh

Katane

Kawata

et al. 2012

Molecular and Cellular Biology

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(58,61). Its concentration in the blood of silkworms was reported to increase during particular stages of metamorphosis, although the physiological role of D-Ser in metamorphosis remains unclear (11). It is also present in the mammalian forebrain, where it persists at high concentrations throughout the life of the animal. DSer is now considered a neuromodulator that binds to the glycinebinding site of the N-methyl-D-Asp (NMDA) receptor, a subtype of the L-glutamate (L-Glu) receptor, and potentiates glutamatergic neurotransmission in the central nervous system (51,60,68). In fact, astroglia-derived D-Ser has been shown to regulate NMDA receptor-dependent long-term potentiation and/or long-term depression, which are basic processes of learning and memory, in the hypothalamic and hippocampal excitatory synapses (25,54). In addition, D-Ser is also found in the cerebellum during the early postnatal period, and it was recently reported that D-Ser derived from the Bergmann glia serves as an endogenous ligand for the ␦2 L-Glu receptor to regulate long-term depression at synapses between parallel fibers and Purkinje cells in the immature cerebellum but not the mature one (31). These lines of evidence suggest the physiological significance of D-Ser in the regulation of higher brain functions through the L-Glu receptors, and indeed, perturbation of D-Ser levels in the central nervous system has now been implicated in the pathophysiology of various neuropsychiatric disorders, including schizophrenia (4, 23, 24, 71), Alzheimer's disease (28, 70), and amyotrophic lateral sclerosis (59).Unlike the tissue-specific expression of D-Ser, substantial amounts of free D-Asp are present in a wide variety of tissues and cells in invertebrates and vertebrates, particularly in the central nervous, neuroendocrine, and endocrine systems. D-Asp is proposed to play an important role in regulating developmental processes, hormone secretion, and steroidogenesis (12,26,35). For instance, it has been reported that in male lizards, intraperitoneally administered D-Asp is taken up rapidly by the testis, which induces a significant increase in testosterone levels and a significant decrease in 17␤-estradiol levels in the testis and plasma (57). Interestingly, a reverse relationship is found between males and females; specifically, in female lizards, exogenous D-Asp induces a significant decrease in testosterone levels in the ovary and plasma, while it enhances follicular production of 17␤-estradiol by upregulating the local aromatase activity (2). Similar findings have also been reported in studies of the green frog (16, 56). These observations suggest that D-Asp is an important regulatory molecule of gonads. In addition, it was recently shown that the amount of D-Asp in human seminal plasma and spermatozoa is significantly reduced in oligoasthenoteratospermic and/or azoospermic donors compared with normospermic donors (14). Moreover, in human female patients undergoing in vitro fertilization, the D-Asp content of the preovulatory follicular fluid ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Spatiotemporal Localization of d-Amino Acid Oxidase and d-Aspartate Oxidases during Development in Caenorhabditis elegans

Saitoh

Katane

Kawata

et al. 2012

Molecular and Cellular Biology

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“…Non-negligible amounts of free D-amino acids have been found in the tissues and physiological fluids of mammals, and some of them have clear physiological functions. For example, D-Ser is synthesized by serine racemase in the mammalian brain [7][8][9], and modulates neurotransmission [10][11][12]. High amounts of D-Asp are observed in the endocrine/neuro-endocrine tissues [13][14][15], and this D-amino acid regulates hormonal synthesis/secretion [16].…”

Section: Introductionmentioning

confidence: 99%

Sleep-Awake Profile Related Circadian D-Alanine Rhythm in Human Serum and Urine

et al. 2017

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The circadian profiles of D-alanine (Ala) amounts in human serum and urine have been clarified using a two-dimensional HPLC system combining a microbore reversed-phase C18 column and a Pirkle-type enantioselective column. The two-dimensional HPLC system enables the determination of trace amounts of D-Ala in the clinical samples without severe interference from intrinsic substances in the human physiological fluids. In the volunteers having normal sleep-awake patterns, the amounts of D-Ala in the serum were high in the late evening and low in the morning. On the other hand, in the volunteers having the reversed sleep-awake patterns, the amounts of D-Ala in the serum were high in the morning and low in the nighttime. The similar circadian changes of D-Ala amounts were observed in the urine. These 24-h profiles of D-Ala are almost the same as those observed in rats and mice, suggesting that D-Ala has fundamental physiological functions related to rest-active conditions in mammals, and could also be useful as the biomarker for sleep-awake profiles.

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“…In this study, we investigated the effects of D-serine and L-serine on polyI:C-induced impairment of sensorimotor gating, emotional and cognitive behaviors, in mice since D-serine has been shown to possess site-and stereo-selective actions on the NMDA-receptor glycine site to which it has a much higher affinity than the corresponding L-amino acid, L-serine (26,27). We also measured the D-serine content, SR and DAAO mRNA levels, and DAAO activity in the brain.…”

Section: Introductionmentioning

confidence: 99%

D-Serine Ameliorates Neonatal PolyI:C Treatment^|^ndash;Induced Emotional and Cognitive Impairments in Adult Mice

Nagai

Kitahara

et al. 2012

J Pharmacol Sci

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Abstract. Polyriboinosinic-polyribocytidilic acid (polyI:C) is a synthetic analog that elicits virallike immune responses in mammals. We have recently found that polyI:C treatment in neonatal mice induced abnormalities of emotional, cognitive, and sensorimotor gating and dysfunction of glutamatergic neurotransmission in adulthood. In this study, we investigated the effect of the NMDA-receptor co-agonist D-serine on polyI:C-induced behavioral abnormalities in mice. Neonatal ICR mice were repeatedly injected with polyI:C for 5 days from postnatal day 2 to 6. At 10 weeks, sensorimotor gating function was analyzed in the prepulse inhibition (PPI) test. Emotional function was analyzed in open field and social interaction tests. Cognitive function was analyzed by novel object recognition tests. D-Serine dose-dependently improved polyI:C-induced impairment of emotional and cognitive behaviors whereas it had no effect on PPI deficit in adults. The ameliorating effects of D-serine were antagonized by pretreatment with an NMDA-receptor antagonist, MK-801. Although the mRNA level of D-amino acid oxidase (DAAO) was increased in the prefrontal cortex and hippocampus of neonatal polyI:C-treated mice in adulthood, no changes were observed in D-serine content and DAAO enzymatic activity. These results suggest that Dserine ameliorates emotional and cognitive impairments of the polyI:C-treated mice through potentiating NMDA receptor activity.

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Analysis of free d-serine in mammals and its biological relevance

Cited by 131 publications

References 177 publications

Spatiotemporal Localization of d-Amino Acid Oxidase and d-Aspartate Oxidases during Development in Caenorhabditis elegans

Spatiotemporal Localization of d-Amino Acid Oxidase and d-Aspartate Oxidases during Development in Caenorhabditis elegans

Sleep-Awake Profile Related Circadian D-Alanine Rhythm in Human Serum and Urine

D-Serine Ameliorates Neonatal PolyI:C Treatment^|^ndash;Induced Emotional and Cognitive Impairments in Adult Mice

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