Glycine Metabolism and Glycine Synthase Activity during the Postnatal Development of Rat Brain

Lahoya, J.L.; Bénavidès, J.; Ugarte, Magdalena

doi:10.1159/000112379

Cited by 10 publications

(4 citation statements)

References 9 publications

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“…Autoradiographic studies of hippocampus slices have demonstrated that glycine is taken up into astrocytes (Fedele et al, 1993), where the degradation of two glycine molecules produces serine (Daly et al, 1976). This pathway may be relevant to D-serine synthesis, because D-serine is probably concentrated in many of the same protoplasmic astrocytes, and the ontogeny of glycine cleavage activity in cerebellum (Lahoya et al, 1980) closely follows that of D-serine (Fig. 6).…”

Section: Discussionmentioning

confidence: 97%

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Schell¹,

Brady²,

Molliver³

et al. 1997

J. Neurosci.

393

349

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D-Serine is localized in mammalian brain to a discrete population of glial cells near NMDA receptors, suggesting that D-serine is an endogenous agonist of the receptor-associated glycine site. To explore this possibility, we have compared the immunohistochemical localizations of D-serine, glycine, and NMDA receptors in rat brain. In the telencephalon, D-serine is concentrated in protoplasmic astrocytes, which are abundant in neuropil in close vicinity to NMDA receptor 2A/B subunits. Ultrastructural examination of the CA1 region of hippocampus reveals D-serine in the cytosolic matrix of astrocytes that ensheath neurons and blood vessels, whereas NR2A/B is concentrated in dendritic spines. By contrast, glycine immunoreactivity in telencephalon is the lowest in brain. During postnatal week 2, D-serine levels in cerebellum are comparable to those in adult cerebral cortex but fall to undetectable levels by day 26.During week 2, we observe parallel ontogeny of D-serine in Bergmann glia and NR2A/B in Purkinje cells, suggesting a role for astrocytic D-serine in NMDA receptor-mediated synaptogenesis. D-Serine in the radial processes of Bergmann glia is also well positioned to regulate NMDA receptor-dependent granule cell migration. In the inner granule layer, D-serine is found transiently in protoplasmic astrocytes surrounding glomeruli, where it could regulate development of the mossy fiber/granule cell synapse. D-Serine seems to be the endogenous ligand of glycine sites in the telencephalon and developing cerebellum, whereas glycine predominates in the adult cerebellum, olfactory bulb, and hindbrain. Key words: D-serine; glycine; NMDA receptor; glia; D-amino acid; cerebellumActivation of NMDA receptor channels requires both glutamate and stimulation of a "glycine site" (Johnson and Ascher, 1987;Reynolds et al., 1987;Kemp and Leeson, 1993). Neurophysiological studies of expressed NMDA receptors indicate that with certain combinations of NR1 and NR2 subunits, D-serine is up to three times more potent than glycine at the glycine site (Matsui et al., 1995;Priestley et al., 1995). Although D-amino acids have long been known to exist in bacteria, worms, and insects (Corrigan, 1969), only very recently have high levels of D-serine been demonstrated in mammalian tissues, especially in the brain (Hashimoto et al., 1992a(Hashimoto et al., , 1993aNagata, 1992;Chouinard et al., 1993;Nagata et al., 1994).We have mapped D-serine immunohistochemically in rat brain and observed a pattern that parallels the localization of D-serine binding sites associated with NMDA receptors in the forebrain (Schell et al., 1995). D-Serine is concentrated in gray matter regions enriched in NMDA receptors and is selectively localized to protoplasmic astrocytes. We have also demonstrated that agonists of non-NMDA receptors enhance the efflux of preloaded D-serine from cultures of cortical type 2 astrocytes. These data suggest that D-serine is an endogenous ligand at the glycine site of many NMDA receptors and that glutamate releases D-serine from glial ...

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Section: Discussionmentioning

confidence: 97%

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Schell¹,

Brady²,

Molliver³

et al. 1997

J. Neurosci.

393

349

View full text Add to dashboard Cite

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“…We observed highest glycine concentrations at P10. Others have reported that the rate of glycine synthesis peaks around 10–15 days after birth (Lahoya et al. 1980; Benítez‐Diaz et al.…”

Section: Discussionmentioning

confidence: 99%

Neurochemical profile of the developing mouse cortex determined by in vivo¹H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia

Kulak¹,

Duarte

Q.³

et al. 2010

Journal of Neurochemistry

102

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The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.

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“…Like for NAAG, the highest glycine concentrations in the brain are observed at P10 and decline until adulthood (Kulak et al, 2010). In fact, the rate of glycine synthesis peaks around 10-15 days after birth (Benítez-Diaz et al, 2003;Lahoya et al, 1980) and likewise, during this period, glycine receptors undergo a major switch of the relative expression of glycinergic subunits (Lynch, 2004). It is interesting to note that the increase in levels of excitatory neurotransmitters, glutamate and aspartate (NMDA receptor agonists), is paralleled by a reduction in the concentration of its modulator NAAG as well as its co-agonist glycine.…”

Section: Neurotransmitter Metabolismmentioning

confidence: 99%

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

et al. 2012

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Glycine Metabolism and Glycine Synthase Activity during the Postnatal Development of Rat Brain

Cited by 10 publications

References 9 publications

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Neurochemical profile of the developing mouse cortex determined by in vivo¹H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

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Glycine Metabolism and Glycine Synthase Activity during the Postnatal Development of Rat Brain

Cited by 10 publications

References 9 publications

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Neurochemical profile of the developing mouse cortex determined by in vivo1H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

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Product

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Neurochemical profile of the developing mouse cortex determined by in vivo¹H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia