Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-23T21:46:49.717Z Has data issue: false hasContentIssue false
  • English
  • Français

D-Serine in Neurobiology: CNS Neurotransmission and Neuromodulation

Published online by Cambridge University Press:  23 September 2014

Sanaa K. Bardaweel ,
Muhammed Alzweiri  and
Aman A. Ishaqat
Sanaa K. Bardaweel*
Affiliation:
Department of Pharmaceutical Sciences, Faculty of Pharmacy, the University of Jordan, Amman, Jordan
Muhammed Alzweiri
Affiliation:
Department of Pharmaceutical Sciences, Faculty of Pharmacy, the University of Jordan, Amman, Jordan
Aman A. Ishaqat
Affiliation:
Department of Pharmaceutical Sciences, Faculty of Pharmacy, the University of Jordan, Amman, Jordan
*
Department of Pharmaceutical Sciences, Faculty of Pharmacy, the University of Jordan, Queen Rania Street, Amman 11942, Jordan. email: [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Homochirality is fundamental for life. L-Amino acids are exclusively used as substrates for the polymerization and formation of peptides and proteins in living systems. However, D- amino acids were recently detected in various living organisms, including mammals. Of these D-amino acids, D-serine has been most extensively studied. D-Serine was found to play an important role as a neurotransmitter in the human central nervous system (CNS) by binding to the N-methyl- D-aspartate receptor (NMDAr). D-Serine binds with high affinity to a co-agonist site at the NMDAr and, along with glutamate, mediates several vital physiological and pathological processes, including NMDAr transmission, synaptic plasticity and neurotoxicity. Therefore, a key role for D-serine as a determinant of NMDAr mediated neurotransmission in mammalian CNS has been suggested. In this context, we review the known functions of D-serine in human physiology, such as CNS development, and pathology, such as neuro-psychiatric and neurodegenerative diseases related to NMDAr dysfunction.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 41 , Issue 2 , March 2014 , pp. 164 - 176
Copyright
Copyright © The Canadian Journal of Neurological 2014

References

1.Lamzin, VS, Dauter, Z, Wilson, KS.How nature deals with stereoisomers. Curr Opin Struct Biol. 1995;5:830–6.CrossRefGoogle ScholarPubMed
2.Mason, SF.Origins of biomolecular handedness. Nature. 1984;311:19–23.CrossRefGoogle ScholarPubMed
3.Prelog, V.Chirality in chemistry. Science. 1976;193:17–24.Google Scholar
4.Auclair, JL, Patton, RL.On the occurrence of D-alanine in the haemolymph of the milkweed bug, oncopeltus fasciatus. Rev Can Biol. 1950;1:3–8.Google Scholar
5.Beatty, I, Magrath, D, Ennor, A.Occurrence of D-serine in lombricine. Nature. 1959;183:591.Google ScholarPubMed
6.Corrigan, JJ, Srinivasan, NG.The occurrence of certain D-amino acids in insects. Biochemistry. 1966;5:1185–90.Google Scholar
7.Kreil, G.Peptides containing a D-amino acid from frogs and molluscs. J Biol Chem. 1994;269:10967–70.CrossRefGoogle ScholarPubMed
8.Preston, RL.Occurrence of D-amino acids in higher organisms: a survey of the distribution of D-amino acids in marine vertebrates. Comp Biochem Physiol B. 1987;87:55–62.CrossRefGoogle Scholar
9.Dunlop, DS, Neidle, A, McHale, D, Dunlop, DM, Lajtha, A.The presence of free D-aspartic acid in rodents and man. Biochem Biophys Res Commun. 1986;141:27–32.CrossRefGoogle ScholarPubMed
10.Hashimoto, A, Nishikawa, T, Hayashi, T, et al. The presence of free D-serine in rat brain. FEBS Lett. 1992;269:33–6.Google Scholar
11.Hashimoto, A, Kumashiro, S, Nishikawa, T, et al. Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex. J Neurochem. 1993;61:348–51.Google Scholar
12.Gustafson, EC, Stevens, ER, Wolosker, H, Miller, RF.Endogenous D-serine contributes to NMDA receptor-mediated light-evoked responses in the vertebrate retina. J Neurophysiol. 2007;98:122–30.Google Scholar
13.Junjaud, G, Rouaud, E, Turpin, F, Mothet, JP, Billard, JM.Age-related effects of the neuromodulator D-serine on neurotransmission and synaptic potentiation in the CA1 hippocampal area of the rat. J Neurochem. 2006;98:1159–66.CrossRefGoogle ScholarPubMed
14.Mothet, JP, Parent, AT, Wolosker, H, et al. D-Serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA. 2000;97:4926–31.Google Scholar
15.Stevens, ER, Esguerra, M, Kim, PM, et al. D-Serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors. Proc Natl Acad Sci USA. 2003;100:6789–94.Google Scholar
16.Panatier, A, Theodosis, DT, Mothet, JP, et al. Glia derived D-serine controls NMDA receptor activity and synaptic memory. Cell. 2006;125:775–84.Google Scholar
17.Yang, Y, Ge, W, Chen, Y, et al. Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proc Natl Acad Sci USA. 2003;100:15194–9.Google Scholar
18.Yang, S, Qiao, H, Wen, L, Zhou, W, Zhang, Y.D-Serine enhances impaired long-term potentiation in CA1 subfield of hippocampal slices from aged senescence-accelerated mouse prone/8. Neurosci Lett. 2005;379:7–12.Google Scholar
19.Kim, PM, Aizawa, H, Kim, PS, et al. Serine racemase: activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration. Proc Natl Acad Sci USA. 2005;102:2105–10.Google Scholar
20.Katsuki, H, Nonaka, M, Shirakawa, H, Kume, T, Akaike, A.Endogenous D-serine is involved in induction of neuronal death by N-methyl-D-aspartate and simulated ischemia in rat cerebrocortical slices. J Pharmacol Exp Ther. 2004;311:836–44.Google Scholar
21.Kartvelishvily, E, Shleper, M, Balan, L, Dumin, E, Wolosker, H.Neuron-derived D-serine release provides a novel means to activate N-methyl-D-aspartate receptors. J Biol Chem. 2006;281:14151–62.Google Scholar
22.Katsuki, H, Watanabe, Y, Fujimoto, S, Kume, T, Akaike, A.Contribution of endogenous glycine and D-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures. Life Sci. 2007;81:740–9.Google Scholar
23.Sasabe, J, Chiba, T, Yamada, M, et al. D-Serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J. 2007;26:4149–59.CrossRefGoogle ScholarPubMed
24.Shleper, M, Kartvelishvily, E, Wolosker, H.D-Serine is the dominant endogenous coagonist for NMDA receptor neurotoxicity in organotypic hippocampal slices. J Neurosci. 2005;25:9413–7.Google Scholar
25.Wu, SZ, Bodles, AM, Porter, MM, Griffin, WS, Basile, AS, Barger, SW.Induction of serine racemase expression and D-serine release from microglia by amyloid beta-peptide. J Neuroinflamm. 2004;1:2–13Google Scholar
26.Schell, MJ, Molliver, ME, Snyder, SH.D-Serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release. Proc Natl Acad Sci USA. 1995;92:3948–52.Google Scholar
27.Puyal, J, Martineau, M, Mothet, JP, Nicolas, MT, Raymond, J.Changes in D-serine levels and localization during postnatal development of the rat vestibular nuclei. J Comp Neurol. 2006; 497:610–21.Google Scholar
28.Van Horn, MR, Sild, M, Ruthazer, ES.D-Serine as a gliotransmitter and its roles in brain development and disease. Front Cell Neurosci. 2013;7:39–52.Google Scholar
29.De Miranda, J, Panizzutti, R, Foltyn, VN, Wolosker, H.Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine. Proc Natl Acad Sci USA. 2002;99:14542–7.Google Scholar
30.Wolosker, H, Blackshaw, S, Snyder, SH.Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission. Proc Natl Acad Sci USA. 1999;96:13409–14.Google Scholar
31.Wolosker, H, Sheth, KN, Takahashi, M, et al. Purification of serine racemase: biosynthesis of the neuromodulator D-serine. Proc Natl Acad Sci USA. 1999;96:721–5.Google Scholar
32.Cook, SP, Galve-Roperh, I, Martinez Del Pozo, A, Rodriguez-Crespo, I.Direct calcium binding results in activation of brain serine racemase. J Biol Chem. 2002;277:27782–92.Google Scholar
33.Neidle, A, Dunlop, DS.Allosteric regulation of mouse brain serine racemase. Neurochem Res. 2002;27:1719–24.CrossRefGoogle ScholarPubMed
34.Strisovsky, K, Jiraskova, J, Barinka, C, et al. Mouse brain serine racemase catalyzes specific elimination of L-serine to pyruvate. FEBS Lett. 2003;535:44–8.Google Scholar
35.Wang, LZ, Zhu, XZ.Spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase during mouse postnatal development. Acta Pharmacol Sin. 2003;24:965–74.Google Scholar
36.De Miranda, J, Santoro, A, Engelender, S, Wolosker, H.Human serine racemase: molecular cloning, genomic organization and functional analysis. Gene. 2000;256:183–8.CrossRefGoogle ScholarPubMed
37.Basu, AC, Tsai, GE, Hani, L, et al. Abnormal sensory gating, reversal of spatial memory, and anxiety-like behavior in serine racemase knockout mice. Soc Neurosci Abstr. 2007;275:3514–26.Google Scholar
38.Ma, CL, Tsai, GE, Coyle, JT, Basu, AC, Bergeron, R.Serine racemase null mutant mice show disrupted NMDA receptor function at the hippocampal schaffer collateral-CA1 pyramidal cell synapse. Soc Neurosci Abstr. 2007;576.Google Scholar
39.Mustafa, AK, Ehmsen, JT, Zeynalov, E, et al. D-Serine deficient mice display NMDA receptor dysfunction and reduced stroke damage. Soc Neurosci Abstr. 2007;576.Google Scholar
40.Zhao, YL, Takata, Y, Hashimoto, K, Sakimura, K, Mori, H.Study of D-serine function in vivo by establishing and analysis of serine racemase knockout mouse. Neurosci Res. 2007;58:346–52.Google Scholar
41.Benneyworth, MA, Li, Y, Basu, AC, Bolshakov, VY, Coyle, JT.Cell selective conditional null mutations of serine racemase demonstrate a predominate localization in cortical glutamatergic neurons. Cell Mol Neurobiol. 2012;32:613–24.Google Scholar
42.Foltyn, VN, Bendikov, I, De Miranda, J, et al. Serine racemase modulates intracellular D-serine levels through an alpha, beta-elimination activity. J Biol Chem. 2005;3:1754–63.Google Scholar
43.Furuya, S, Tabata, T, Mitoma, J, et al. L-Serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons. Proc Natl Acad Sci USA. 2000;97:11528–33.Google Scholar
44.Yamasaki, M, Yamada, K, Furuya, S, Mitoma, J, Hirabayashi, Y, Watanabe, M.3-Phosphoglycerate dehydrogenase, a key enzyme for L-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain. J Neurosci. 2001;21:7691–704.Google Scholar
45.Wolosker, H.Serine racemase and the serine shuttle between neurons and astrocytes. Biochim Biophys Acta. 2011;1814:1558–66.CrossRefGoogle ScholarPubMed
46.Krebs, HA.Metabolism of amino acids. III. Determination of amino acids. Biochem J. 1935;29:1620–44.Google Scholar
47.Pollegioni, L, Harris, CM, Molla, G, Pilone, MS, Ghisla, S.Identification and role of ionizing functional groups at the active center of Rhodotorula gracilis D-amino acid oxidase. FEBS Lett. 2001;507:323–6.Google Scholar
48.Hashimoto, A, Nishikawa, T, Konno, R, et al. Free D-serine, D-aspartate and D-alanine in central nervous system and serum in mutant mice lacking D-amino acid oxidase. Neurosci Lett. 1993;152:33–6.Google Scholar
49.Morikawa, A, Hamase, K, Inoue, T, Konno, R, Niwa, A, Zaitsu, K.Determination of free D-aspartic acid, D-serine and D-alanine in the brain of mutant mice lacking D-amino acid oxidase activity. J Chromatogr B Biomed Sci Appl. 2001;757:119–25.Google Scholar
50.D’Aniello, A, Vetere, A, Petrucelli, L.Further study on the specificity of D-amino acid oxidase and D-aspartate oxidase and time course for complete oxidation of D-amino acids. Comp Biochem Physiol B. 1993;105:731–4.Google Scholar
51.Nagata, Y, Konno, R, Yasumura, Y, Akino, T.Involvement of D-amino acid oxidase in elimination of free D-amino acids in mice. Biochem J. 1989;257:291–2.Google Scholar
52.Urai, Y, Jinnouchi, O, Kwak, KT, Suzue, A, Nagahiro, S, Fukui, K.Gene expression of D-amino acid oxidase in cultured rat astrocytes: regional and cell type specific expression. Neurosci Lett. 2002;324:101–4.Google Scholar
53.Danysz, W, Parsons, CG.Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications. Pharmacol Rev. 1998;4:597–664.Google Scholar
54.Paoletti, P, Neyton, J.NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol. 2007;7:39–47.Google Scholar
55.McBain, CJ, Kleckner, NW, Wyrick, S, Dingledine, R.Structural requirements for activation of the glycine coagonist site of N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Mol Pharmacol. 1989;36:556–65.Google Scholar
56.Fadda, E, Danysz, W, Wroblewski, JT, Costa, E.Glycine and D-serine increase the affinity of N-methyl-D-aspartate sensitive glutamate binding sites in rat brain synaptic membranes. Neuropharmacology. 1988;27:1183–5.Google Scholar
57.Lerma, J, Zukin, RS, Bennett, MV.Glycine decreases desensitization of N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus oocytes and is required for NMDA responses. Proc Natl Acad Sci USA. 1990;87:2354–8.Google Scholar
58.Nong, Y, Huang, YQ, Ju, W, et al. Glycine binding primes NMDA receptor internalization. Nature. 2003;422:302–7.Google Scholar
59.Furukawa, H, Gouaux, E.Mechanisms of activation, inhibition and specificity: crystal structures of the NMDA receptor NR1 ligand-binding core. EMBO J. 2003;22:2873–85.Google Scholar
60.Constantine-Paton, M, Cline, HT, Debski, E.Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways. Annu Rev Neurosci. 1990;13:129–54.Google Scholar
61.Henneberger, C, Papouin, T, Oliet, SH, Rusakov, DA.Long-term potentiation depends on release of D-serine from astrocytes. Nature. 2010;463:232–6.Google Scholar
62.Stevens, ER, Gustafson, EC, Sullivan, SJ, Esguerra, M, Miller, RF.Light-evoked NMDA receptor-mediated currents are reduced by blocking D-serine synthesis in the salamander retina. Neuroreport. 2010;21:239–44.Google Scholar
63.Fossat, P, Turpin, FR, Sacchi, S, et al. Glial D-serine gates NMDA receptors at excitatory synapses in prefrontal cortex. Cereb Cortex. 2012;22:595–606.Google Scholar
64.Kaufman, AM, Milnerwood, AJ, Sepers, MD, et al. Opposing roles of synaptic and extrasynaptic NMDA receptor signaling in cocultured striatal and cortical neurons. J Neurosci. 2012;32:3992–4003.Google Scholar
65.Papouin, T, Ladépěche, L, Ruel, J, et al. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists. Cell. 2012;150:633–46.Google Scholar
66.Mothet, JP, Rouaud, E, Sinet, PM, et al. A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory. Aging Cell. 2006;5:267–74.Google Scholar
67.Berger, AJ, Dieudonne, S, Ascher, P.Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J Neurophysiol. 1998;80:3336–40.Google Scholar
68.Bergeron, R, Meyer, TM, Coyle, JT, Greene, RW.Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proc Natl Acad Sci USA. 1998;95:15730–4.Google Scholar
69.Sakata, Y, Owada, Y, Sato, K, et al. Structure and expression of the glycine cleavage system in rat central nervous system. Brain Res Mol Brain Res. 2001;94:119–30.Google Scholar
70.Sato, K, Yoshida, S, Fujiwara, K, Tada, K, Tohyama, M.Glycine cleavage system in astrocytes. Brain Res. 1991;567:64–70.Google Scholar
71.Zafra, F, Aragon, C, Gimenez, C.Molecular biology of glycinergic neurotransmission. Mol Neurobiol. 1997;14:117–42.Google Scholar
72.Ribeiro, CS, Reis, M, Panizzutti, R, de Miranda, J, Wolosker, H.Glial transport of the neuromodulator D-serine. Brain Res. 2002;929:202–9.Google Scholar
73.Fukasawa, Y, Segawa, H, Kim, JY, et al. Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids. J Biol Chem. 2000;275:9690–8.Google Scholar
74.Helboe, L, Egebjerg, J, Moller, M, Thomsen, C.Distribution and pharmacology of alanine-serine-cysteine transporter 1 (asc-1) in rodent brain. Eur J Neurosci. 2003;18:2227–38.Google Scholar
75.Matsuo, H, Kanai, Y, Tokunaga, M, et al. High affinity D- and L-serine transporter Asc-1: cloning and dendritic localization in the rat cerebral and cerebellar cortices. Neurosci Lett. 2004;358:123–6.Google Scholar
76.Nakauchi, J, Matsuo, H, Kim, DK, et al. Cloning and characterization of a human brain Na(+)-independent transporter for small neutral amino acids that transports D-serine with high affinity. Neurosci Lett. 2000;287:231–5.Google Scholar
77.Hayashi, F, Takahashi, K, Nishikawa, T.Uptake of D- and L-serine in C6 glioma cells. Neurosci Lett. 1997;239:85–8.Google Scholar
78.Rutter, AR, Fradley, RL, Garrett, EM, et al. Evidence from gene knockout studies implicates Asc-1 as the primary transporter mediating D-serine reuptake in the mouse CNS. Eur J Neurosci. 2007;25:1757–66.Google Scholar
79.Shao, Z, Kamboj, A, Anderson, CM.Functional and immunocytochemical characterization of D-serine transporters in cortical neuron and astrocyte cultures. J Neurosci Res. 2009;87:2520–30.Google Scholar
80.Horiike, K, Tojo, H, Arai, R, Nozaki, M, Maeda, T.D-Amino-acid oxidase is confined to the lower brain stem and cerebellum in rat brain: regional differentiation of astrocytes. Brain Res. 1994;652:297–303.Google Scholar
81.Hashimoto, A.Effect of the intracerebroventricular and systemic administration of L-serine on the concentrations of D- and L-serine in several brain areas and periphery of rat. Brain Res. 2002;955:214–20.Google Scholar
82.Boehning, D, Snyder, SH.Novel neural modulators. Annu Rev Neurosci. 2003;26:105–31.Google Scholar
83.Hashimoto, A, Oka, T, Nishikawa, T.Anatomical distribution and postnatal changes in endogenous free D-aspartate and D-serine in rat brain and periphery. Eur J Neurosci. 1995;7:1657–63.Google Scholar
84.Chahal, H, D’Souza, SW, Barson, AJ, Slater, P.Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain. Arch Dis Child Fetal Neonatal Ed. 1998;78:F116–20.Google Scholar
85.Panigrahy, A, Rosenberg, PA, Assmann, S, Foley, EC, Kinney, HC.Differential expression of glutamate receptor subtypes in human brainstem sites involved in perinatal hypoxia-ischemia. J Comp Neurol. 2000;427:196–208.Google Scholar
86.Piggott, MA, Perry, EK, Perry, RH, Court, JA.[3H]MK-801 binding to the NMDA receptor complex, and its modulation in human frontal cortex during development and aging. Brain Res. 1992;588:277–86.Google Scholar
87.Slater, P, McConnell, SE, D’Souza, SW, Barson, AJ.Postnatal changes in N-methyl-D-aspartate receptor binding and stimulation by glutamate and glycine of [3H]-MK-801 binding in human temporal cortex. Br J Pharmacol. 1993;108:1143–9.Google Scholar
88.Crair, MC, Malenka, RC.A critical period for long-term potentiation at thalamocortical synapses. Nature. 1995;375:325–8.Google Scholar
89.Feldman, DE, Nicoll, RA, Malenka, RC, Isaac, JT.Long-term depression at thalamocortical synapses in developing rat somatosensory cortex. Neuron. 1998;21:347–57.Google Scholar
90.Ramoa, AS, McCormick, DA.Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse. J Neurosci. 1994;14:2098–105.Google Scholar
91.Fuchs, SA, Dorland, L, de Sain-van der Velden, MG, et al. D-Serine in the developing human central nervous system. Ann Neurol. 2006;60:476–80.Google Scholar
92.Komuro, H, Rakic, P.Modulation of neuronal migration by NMDA receptors. Science. 1993;260:95–7.Google Scholar
93.Hepner, F, Pollak, A, Ulfig, N, Yae-Kyung, M, Lubec, G.Mass spectrometrical analysis of human serine racemase in foetal brain. J Neural Transm. 2005;112:805–11.Google Scholar
94.Adesnik, H, Li, G, During, MJ, Pleasure, SJ, Nicoll, RA.NMDA receptors inhibit synapse unsilencing during brain development. Proc Natl Acad Sci USA. 2008;105:5597–602.Google Scholar
95.Rabacchi, S, Bailly, Y, Delhaye-Bouchaud, N, Mariani, J.Involvement of the N-methyl-D-aspartate (NMDA) receptor in synapse elimination during cerebellar development. Science. 1992;256:1823–5.Google Scholar
96.Bliss, TV, Collingridge, GL.A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361:31–9.CrossRefGoogle ScholarPubMed
97.Basu, AC, Tsai, GE, Ma, CL, et al. Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior. Mol Psychiatry. 2009;14:719–27.CrossRefGoogle ScholarPubMed
98.Almond, SL, Fradley, RL, Armstrong, EJ, et al. Behavioral and biochemical characterization of a mutant mouse strain lacking D-amino acid oxidase activity and its implications for schizophreni. Mol Cell Neurosci. 2006;32:324–34.Google Scholar
99.Maekawa, M, Watanabe, M, Yamaguchi, S, Konno, R, Hori, Y.Spatial learning and long-term potentiation of mutant mice lacking D-amino-acid oxidase. Neurosci Res. 2005;53:34–8.Google Scholar
100.Turpin, FR, Potier, B, Dulong, JR, et al. Reduced serine racemase expression contributes to age-related deficits in hippocampal cognitive function. Neurobiol Aging. 2009;8:1495–504.Google Scholar
101.Choi, DW, Rothman, SM.The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci. 1990;13:171–82.Google Scholar
102.Inoue, R, Hashimoto, K, Harai, T, Mori, H.NMDA- and beta-amyloid1-42-induced neurotoxicity is attenuated in serine racemase knock-out mice. J Neurosci. 2008;28:14486–91.Google Scholar
103.Paul, P, de Belleroche, J.The role of D-amino acids in amyotrophic lateral sclerosis pathogenesis: a review. Amino Acids. 2012;43:1823–31.Google Scholar
104.Bruijn, LI, Miller, TM, Cleveland, DW.Unraveling the mechanisms involved in motor neurondegeneration in ALS. Annu Rev Neurosci. 2004;27:723–49.Google Scholar
105.Rothstein, JD, Tsai, G, Kuncl, RW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol. 1990;28:18–25.Google Scholar
106.Mitchell, JPaul, P, Chen, HJ, et al. Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase. Proc Natl Acad Sci USA. 2010;107:7556–61.Google Scholar
107.Olney, JW, Wozniak, DF, Farber, NB.Excitotoxic neurodegeneration in Alzheimer disease. New hypothesis and new therapeutic strategies. Arch Neurol. 1997;54:1234– 40.Google Scholar
108.Kornhuber, J, Weller, M.Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for neurodegenerative pharmacotherapy. Biol Psychiatry. 1997;41:135–44.Google Scholar
109.Newcomer, JW, Krystal, JH.NMDA receptor regulation of memory and behavior in humans. Hippocampus. 2001;11:529–42.CrossRefGoogle ScholarPubMed
110.Loftis, JM, Janowsky, A.The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther. 2003;97:55–85.Google Scholar
111.Maragos, WF, Chu, DC, Young, AB, D’Amato, CJ, Penney, JB. JrLoss of hippocampal [3H]TCP binding in Alzheimer’s disease. Neurosci Lett. 1987;74:371–6.Google Scholar
112.Procter, AW, Wong, EH, Stratmann, GC, Lowe, SL, Bowen, DM.Reduced glycine stimulation of [3H]MK-801 binding in Alzheimer’s disease. J Neurochem. 1989;53:698–704.Google Scholar
113.Sze, C, Bi, H, Kleinschmidt-DeMasters, BK, Filley, CM, Martin, LJ.N-Methyl-D-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer’s disease. J Neurol Sci. 2001;182:151–9.Google Scholar
114.Reisberg, B, Doody, R, Stoffler, A, Schmitt, F, Ferris, S, Mobius, HJ.Memantine Study Group. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003;348:1333–41.Google Scholar
115.Suh, YH, Checler, F.Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer’s disease. Pharmacol Rev. 2002;54:469–525.Google Scholar
116.Brito-Moreira, J, Paula-Lima, AC, Bomfim, TR, et al. Abeta oligomers induce glutamate release from hippocampal neurons. Curr Alzheimer Res. 2011;5:552–62.Google Scholar
117.Wu, S, Basile, AS, Barger, SW.Induction of serine racemase expression and D-serine release from microglia by secreted amyloid precursor protein (sAPP). Curr Alzheimer Res. 2007;4:243–51.Google Scholar
118.Peterson, SL.Anticonvulsant drug potentiation by glycine in maximal electroshock seizures is mimicked by D-serine and antagonized by 7-chlorokynurenic acid. Eur J Pharmacol. 1991;199:341–8.Google Scholar
119.Loscher, W, Wlaz, P, Rundfeldt, C, Baran, H, Honack, D.Anticonvulsant effects of the glycine/NMDA receptor ligands D-cycloserine and D-serine but not R-(+)-HA-966 in amygdalakindled rats. Br J Pharmacol. 1994;112:97–106.Google Scholar
120.Schwartz, BL, Hashtroudi, S, Herting, RL, Schwartz, P, Deutsch, SI.D-Cycloserine enhances implicit memory in Alzheimer patients. Neurology. 1996;46:420–4.Google Scholar
121.Tsai, G, Falk, WE, Gunther, J, Coyle, JT.Improved cognition in Alzheimer’s disease with short-term D-cycloserine treatment. Am J Psychiatr. 1999;156:467–9.Google Scholar
122.Andersen, JM, Fonnum, F, Myhrer, T.D-Serine alleviates retrograde amnesia of a visual discrimination task in rats with a lesion of the perirhinal cortex. Brain Res. 2003;979:240–4.Google Scholar
123.Singh, L, Oles, RJ, Tricklebank, MD.Modulation of seizure susceptibility in the mouse by the strychnine-insensitive glycine recognition site of the NMDA receptor/ion channel complex. Br J Pharmacol. 1990;99:285–8.Google Scholar
124.De, SG, Trimarchi, GR, Sinopoli, S, Masuda, Y, De, SA.Anticonvulsant effects of U-54494A and U-50488 H in genetically epilepsy-prone rats and DBA/2 mice: a possible involvement of glycine/NMDA receptor complex. Gen Pharmacol. 1993;24:439–47.Google Scholar
125.Peterson, SL.Infusion of NMDA antagonists into the nucleus reticularis pontis oralis inhibits the maximal electroshock seizure response. Brain Res. 1995;702:101–10.Google Scholar
126.Liu, YH, Wang, L, Wei, LC, Huang, YG, Chen, LW.Up-regulation of D-serine might induce GABAergic neuronal degeneration in the cerebral cortex and hippocampus in the mouse pilocarpine model of epilepsy. Neurochem Res. 2009;34:1209–18.Google Scholar
127.Rossetti, AO, Logroscino, G, Liaudet, L, et al. Status epilepticus: an independent outcome predictor after cerebral anoxia. Neurology. 2007;69:255–60.Google Scholar
128.Ryu, HJ, Kim, JE, Yeo, SI, et al. Potential roles of D-serine and serine racemase in experimental temporal lobe epilepsy. J Neurosci Res. 2010;88:2469–82.Google Scholar
129.Robinson, JL, Monkul, ES, Tordesillas-Gutiérrez, D, et al. Frontolimbic circuitry in euthymic bipolar disorder: evidence for prefrontal hyperactivation. Psychiatry Res. 2008;164:106–13.Google Scholar
130.American Psychatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th ed.Washington, DC. American Psychiatric Association 1994:866 p.Google Scholar
131.Chen, YS, Akula, N, Detera-Wadleigh, SD, et al. Findings in an independent sample support an association between bipolar affective disorder and the G72/G30 locus on chromosome 13q33. Mol Psychiatry. 2004;9:87–92.Google Scholar
132.Hattori, E, Liu, C, Badner, JA, et al. Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series. Am J Hum Genet. 2003;72:1131–40.Google Scholar
133.Muller, DJ, Zai, CC, Shinkai, T, Strauss, J, Kennedy, JL.Association between the DAOA/G72 gene and bipolar disorder and meta-analyses in bipolar disorder and schizophrenia. Bipolar Disord. 2011;13:198–207.Google Scholar
134.Prata, D, Breen, G, Osborne, S, Munro, J, Clair, D St, Collier, D.Association of DAO and G72(DAOA)/G30 genes with bipolar affective disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:914–7.Google Scholar
135.Schumacher, J, Jamra, RA, Freudenberg, J, et al. Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder. Mol Psychiatry. 2004;9:203–7.Google Scholar
136.Williams, NM, Green, EK, Macgregor, S, et al. Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder. Arch Gen Psychiatry. 2006;63:366–73.Google Scholar
137.Zhang, Z, Li, Y, Zhao, Q, et al. First evidence of association between G72 and bipolar disorder in the Chinese Han population. Psychiatr Genet. 2009;19:151–3.Google Scholar
138.Abou, JR, Gobina, CM, Becker, T, et al. Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder. Psychiatr Genet. 2008;18:199–203.Google Scholar
139.Hashimoto, K, Sawa, A, Iyo, M.Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007;62:1310–6.Google Scholar
140.Robertson, CM, Finer, NN, Grace, MG.School performance of survivors of neonatal encephalopathy associated with birth asphyxia at term. J Pediatr. 1989;114:753–60.Google Scholar
141.Shankaran, S, Woldt, E, Koepke, T, Bedard, MP, Nandyal, R.Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev. 1991;25:135–48.Google Scholar
142.Sattler, R, Tymianski, M.Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol. 2001;24:107–29.Google Scholar
143.Mustafa, AK, Ahmad, AS, Zeynalov, E, et al. Serine racemase deletion protects against cerebral ischemia and excitotoxicity. J Neurosci. 2010;30:1413–6.Google Scholar
144.Goff, DC, Coyle, JT.The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatr. 2001;158:1367–77.Google Scholar
145.Murray, CJL, Lopez, AD, Harvard School of Public Health; World Health Organization, World Bank. The Global Burden of Disease: a Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Published by the Harvard School of Public Health on behalf of the World Health Organization and the World Bank; Distributed by Harvard University Press, Cambridge, MA 1996;vol xxxii.Google Scholar
146.Lisman, JE, Coyle, JT, Green, RW, et al. Circuit-based framework for understanding neurotransmitter and riskgene interactions in schizophrenia. Trends Neurosci. 2008;31:234–42.Google Scholar
147.Janowsky, DS, Risch, C.Amphetamine psychosis and psychotic symptoms. Psychopharmacology. 1979;65:73–7.Google Scholar
148.Seeman, P, Chau-Wong, M, Tedesco, J, Wong, K.Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc Natl Acad Sci U S A. 1975;72:4376–80.Google Scholar
149.Creese, I, Burt, DR, Snyder, SH.Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science. 1976;192:481–3.Google Scholar
150.Tsai, G, Yang, P, Chung, LC, Lange, N, Coyle, JT.D-Serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998;44:1081–9.Google Scholar
151.Lewis, DA, Moghaddam, B.Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations. Arch Neurol. 2006;63:1372–6.Google Scholar
152.Javitt, DC, Zukin, SR.Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991;148:1301–8.Google Scholar
153.Krystal, JH, Karper, LP, Seibyl, JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994;51:199–214.Google Scholar
154.Yee, BK, Chang, DT, Feldon, J.The effects of dizocilpine and phencyclidine on prepulse inhibition of the acoustic startle reflex and on prepulse-elicited reactivity in C57BL6 mice. Neuropsychopharmacology. 2004;29:1865–77.Google Scholar
155.Lipina, T, Labrie, V, Weiner, I, Roder, J.Modulators of the glycine site onNMDA receptors, D-serine and ALX 5407, display similar beneficial effects to clozapine in mouse models of schizophrenia. psychopharmacology (Berl). 2005;179:54–67.Google Scholar
156.Mandillo, S, Rinaldi, A, Oliverio, A, Mele, A.Repeated administration of phencyclidine, amphetamine and MK-801 selectively impairs spatial learning in mice: a possible model of psychotomimetic drug-induced cognitive deficits. Behav Pharmacol. 2003;14:533–44.Google Scholar
157.Linn, GS, Negi, SS, Gerum, SV, Javitt, DC.Reversal of phencyclidineinduced prepulse inhibition deficits by clozapine in monkeys. Psychopharmacology. 2003;169:243–9.Google Scholar
158.Mao, CV, Hori, E, Maior, RS, Ono, T, Nishijo, H.A primate model of schizophrenia using chronic PCP treatment. Rev Neurosci. 2008;19:83–9.Google Scholar
159.Thompson, DM, Winsauer, PJ, Mastropaolo, J.Effects of phencyclidine, ketamine and MDMA on complex operant behavior in monkeys. Pharmacol Biochem Behav. 1987;26:401–5.Google Scholar
160.Bubeníková-Valesová, V, Horácek, J, Vrajová, M, Höschl, C.Models of schizophrenia in humans and animals based on inhibition of NMDA receptors. Neurosci Biobehav Rev. 2008;32:1014–23.Google Scholar
161.Bendikov, I, Nadri, C, Amar, S, et al. A CSF and postmortem brain study of D-serine metabolic parameters in schizophrenia. Schizophr Res. 2007;90:41–51.Google Scholar
162.Hashimoto, K, Engberg, G, Shimizu, E, Nordin, C, Lindstrom, LH, Iyo, M.Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:767–9.Google Scholar
163.Hashimoto, K, Fukushima, T, Shimizu, E, et al. Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia. Arch Gen Psychiatry. 2003;60:572–6.Google Scholar
164.Calcia, MA, Madeira, C, Alheira, FV, et al. Plasma levels of D-serine in Brazilian individuals with schizophrenia. Schizophr Res. 2012;142:83–7.Google Scholar
165.Kumashiro, S, Hashimoto, A, Nishikawa, T.Free D-serine in postmortem brains and spinal cords of individuals with and without neuropsychiatric diseases. Brain Res. 1995;681:117–25.Google Scholar
166.Madeira, C, Freitas, ME, Vargas-Lopes, C, Wolosker, H, Panizzutti, R.Increased brain D-amino acid oxidase (DAAO) activity in schizophrenia. Schizophr Res. 2008;101:76–83.Google Scholar
167.Habl, G, Zink, M, Petroianu, G, et al. Increased D-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study. J Neural Transm. 2009;116:1657–65.Google Scholar
168.Allen, NC, Bagade, S, McQueen, MB, et al. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet. 2008;40:827–34.Google Scholar
169.Shi, J, Gershon, ES, Liu, C.Genetic associations with schizophrenia: meta-analyses of 12 candidate genes. Schizophr Res. 2008;10:96–107.Google Scholar
170.Sun, J, Kuo, PH, Riley, BP, Kendler, KS, Zhao, Z.Candidate genes for schizophrenia: a survey of association studies and gene ranking. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1173–81.Google Scholar
171.Burnet, PW, Eastwood, SL, Bristow, GC, et al. D-Amino acid oxidase activity and expression are increased in schizophrenia. Mol Psychiatry. 2008;13:658–60.Google Scholar
172.Kapoor, R, Lim, KS, Cheng, A, Garrick, T, Kapoor, V.Preliminary evidence for a link between schizophrenia and NMDA-glycine site receptor ligand metabolic enzymes, D-amino acid oxidase (DAAO) and kynurenine amino transferase-1 (KAT-1). Brain Res. 2006;1106:205–10.Google Scholar
173.Verrall, L, Walker, M, Rawlings, N, et al. D-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia. Eur J Neurosci. 2007;26:1657–69.Google Scholar
174.Morita, Y, Ujike, H, Tanaka, Y, et al. A genetic variant of the serine racemase gene is associated with schizophrenia. Biol Psychiatry. 2007;61:1200–3.Google Scholar
175.Labrie, V, Fukumura, R, Rastogi, A, et al. Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model. Hum Mol Genet. 2009;18:3227–43.Google Scholar
176.Boks, MP, Rietkerk, T, van de Beek, MH, Sommer, IE, de Koning, TJ, Kahn, RS.Reviewing the role of the genes G72 and DAAO in glutamate neurotransmission in schizophrenia. Eur Neuropsychopharmacol. 2007;17:567–72.Google Scholar
177.Caldinelli, L, Sacchi, S, Molla, G, Nardini, M, Pollegioni, L.Characterization of human DAAO variants potentially related to an increased risk of schizophrenia. Biochim Biophys Acta. 2013;1832:400–10.Google Scholar
178.Chumakov, I, Blumenfeld, M, Guerassimenko, O, et al. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc Natl Acad Sci U S A. 2002;99:13675–80.Google Scholar
179.Detera-Wadleigh, SD, McMahon, FJ.G72/G30 in schizophrenia and bipolar disorder: review and meta-analysis. Biol Psychiatry. 2006;60:106–14.Google Scholar
180.Goldberg, TE, Straub, RE, Callicott, JH, et al. The G72/G30 gene complex and cognitive abnormalities in schizophrenia. Neuropsychopharmacol. 2006;31:2022–32.Google Scholar
181.Korostishevsky, M, Kaganovich, M, Cholostoy, A, et al. Is the G72/G30 locus associated with schizophrenia? Single nucleotide polymorphisms, haplotypes, and gene expression analysis. Biol Psychiatry. 2004;56:169–76.Google Scholar
182.Korostishevsky, M, Kremer, I, Kaganovich, M, et al. Transmission disequilibrium and haplotype analyses of the G72/G30 locus: suggestive linkage to schizophrenia in Palestinian Arabs living in the North of Israel. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:91–5.Google Scholar
183.Wang, X, He, G, Gu, N, et al. Association of G72/G30 with schizophrenia in the Chinese population. Biochem Biophys Res Commun. 2004;319:1281–6.Google Scholar
184.Zou, F, Li, C, Duan, S, et al. A family-based study of the association between the G72/G30 genes and schizophrenia in the Chinese population. Schizophr Res. 2005;73:257–61.Google Scholar
185.Otte, DM, Bilkei-Gorzó, A, Filiou, MD, et al. Behavioral changes in G72/G30 transgenic mice. Eur Neuropsychopharmacol. 2009;5:339–48.Google Scholar
186.Heresco-Levy, U, Javitt, DC, Ebstein, R, et al. D-Serine efficacy as add-on pharmacotherapy to risperi-done and olanzapine for treatment- refractory schizophrenia. Biol Psychiatry. 2005;57:577–85.Google Scholar
187.Kantrowitz, JT, Malhotra, AK, Cornblatt, B, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res. 2010;121:125–30.Google Scholar
188.D’Souza, DC, Radhakrishnan, R, Perry, E, et al. Feasibility, safety, and efficacy of the combination of D-serine and computerized cognitive retraining in schizophrenia: an international collaborative pilot study. Neuropsychopharmacol. 2013;38:492–503.Google Scholar
189.Belmaker, RH, Agam, G.Major depressive disorder. New Engl J Med. 2008;358:55–68.Google Scholar
190.Van Praag, H.Monoamine precursors in depression: present state and prospects. In: Zohar, J, Belmaker, RH, editors. Treating resistant depression. New York: PMA Publishing 1987:279–306Google Scholar
191.Choudary, PV, Molnar, M, Evans, SJ, et al. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci USA. 2005;102:15653–8.Google Scholar
192.Lewy, AJ, Lefler, BJ, Emens, JS, Bauer, VK.The circadian basis of winter depression. Proc Natl Acad Sci USA. 2006;103:7414–9.Google Scholar
193.Duman, RS.Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci. 2009;11:239–55.Google Scholar
194.Malkesman, O, Austin, DR, Tragon, T, et al. Acute D-serine treatment produces antidepressant-like effects in rodents. Int J Neuropsychopharmacol. 2012;8:1135–48.Google Scholar
195.McCullumsmith, RE, Kristiansen, LV, Beneyto, M, Scarr, E, Dean, B, Meador-Woodruff, JH.Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain Res. 2007;1127:108–18.Google Scholar
196.Nudmamud-Thanoi, S, Reynolds, GP.The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neurosci Lett. 2004;372:173–7.Google Scholar
197.Banasr, M, Chowdhury, GM, Terwilliger, R, et al. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry. 2010;15:501–11.Google Scholar
198.Cotter, D, Mackay, D, Landau, S, Kerwin, R, Everall, I.Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry. 2001;58:545–53.Google Scholar
199.Eby, GA, Eby, KL.Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67:362–70.Google Scholar
200.Kroczka, B, Brañski, P, Palucha, A, Pilc, A, Nowak, G.Antidepressant-like properties of zinc in rodent forced swim test. Brain Res Bull. 2001;55:297–300.Google Scholar
201.Kroczka, B, Ziěba, A, Dudek, D, Pilc, A, Nowak, G.Zinc exhibits an antidepressant-like effect in the forced swimming test in mice. Pol J Pharmacol. 2000;52:403–6.Google Scholar
202.Poleszak, E, Szewczyk, B, Wlaź, A, et al. D-Serine, a selective glycine/N-methyl-D-aspartate receptor agonist, antagonizes the antidepressant-like effects of magnesium and zinc in mice. Pharmacol Rep. 2008;60:996–1000.Google Scholar
203.Gelfin, E, Kaufman, Y, Korn-Lubetzki, I, et al. D-Serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson’s disease. Int J Neuropsychopharmacol. 2012;4:543–9.Google Scholar
204.Braak, H, Braak, E.Pathoanatomy of Parkinson’s disease. J Neurol Sci. 2000;247:3–10.Google Scholar
205.Hoehn, MM, Yahr, MD.Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427–42.Google Scholar
206.Starr, MS.Antagonists of glutamate in the treatment of Parkinson’s disease: from laboratory to the clinic. Amino Acids. 1998;14:41–2.Google Scholar
207.Hallett, PJ, Standaert, DG.Rationale for and use of NMDA antagonists in Parkinson’s disease. Pharmacolo Ther. 2004;10:155–74.Google Scholar
208.Johnson, KA, Conn, PJ, Niswender, CM.Glutamate receptors as therapeutic targets for Parkinson’s disease. CNS Neurol Disord Drug Targets. 2009 Dec;8(6):475–91.Google Scholar
209.Crosby, NJ, Deane, KH, Clarke, CE.Amantadine for dyskinesia in Parkinson’s disease. Cochrane Database Syst Rev. 2003;2:3467–81.Google Scholar
210.Del Dotto, P, Pavese, N, Gambaccini, G, et al. Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study. Mov Disord. 2001;3:515–20.Google Scholar
211.Verhagen Metman, L, Blanchet, PJ, van den Munckhof, P, Del Dotto, P, Natté, R, Chase, TN.A trial of dextromethorphan in parkinsonian patients with motor response complications. Mov Disord. 1998;3:414–7.Google Scholar
212.Verhagen Metman, L, Del Dotto, P, van den Munckhof, P, Fang, J, Mouradian, MM, Chase, TN.Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology. 1998;5:1323–6.Google Scholar
213.Blanchet, PJ, Metman, LV, Mouradian, MM, Chase, TN.Acute pharmacologic blockade of dyskinesias in Parkinson’s disease. Mov Disord. 1996;5:580–1.Google Scholar