Skip to main content
SpringerLink
Log in

The Glutamatergic System as Potential Clinical Biomarkers for Blood and Cerebrospinal Fluid Monitoring

  • Protocol
  • First Online:
Book cover Biochemical Approaches for Glutamatergic Neurotransmission

Part of the book series: Neuromethods ((NM,volume 130))

  • 1056 Accesses

Abstract

Glutamate is the most abundant excitatory amino acid in the brain. In addition to the protein structure, it plays important roles in metabolism, nutrition, and signaling via glutamate receptors. Glutamate is synthesized from glutamine by glutaminase, while it is metabolized to the inhibitory amino acid γ-aminobutyric acid (GABA) by glutamic decarboxylase. Thus, the glutamine-glutamate-GABA cycle plays an important role in both excitatory and inhibitory neurotransmissions via glutamate and GABA receptors. Accumulating evidence suggests that abnormalities in glutamatergic neurotransmission via ionotropic and metabotropic glutamate receptors may play crucial roles in the pathophysiology of a variety of psychiatric, neurologic as well as other peripheral disorders. In this chapter, the author discusses the glutamatergic system as potential clinical biomarkers for human blood and cerebrospinal fluid monitoring.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kvamme E (1998) Synthesis of glutamate and its regulation. Prog Brain Res 116:73–85

    Article  CAS  PubMed  Google Scholar 

  2. Hashimoto K (2009) Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 61:105–123

    Article  CAS  PubMed  Google Scholar 

  3. Hashimoto K (2011) The role of glutamate on the action of antidepressants. Prog Neuro-Psychopharmacol Biol Psychiatry 35:1558–1568

    Article  CAS  Google Scholar 

  4. Tokita K, Yamaji T, Hashimoto K (2012) Roles of glutamate signaling in preclinical and/or mechanistic models of depression. Pharmacol Biochem Behav 100:688–704

    Article  CAS  PubMed  Google Scholar 

  5. Hashimoto K, Malchow B, Falkai P, Schmitt A (2013) Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Neurosci 263:367–377

    Article  PubMed  Google Scholar 

  6. Hertz L (2013) The glutamate-glutamine (GABA) cycle: importance of late postnatal development and potential reciprocal interactions between biosynthesis and degradation. Front Endocrinol (Lausanne) 4:59

    CAS  Google Scholar 

  7. Hashimoto K (2014) Targeting of NMDA receptors in new treatments for schizophrenia. Expert Opin Ther Targets 18:1049–1063

    Article  CAS  PubMed  Google Scholar 

  8. Hashimoto K (2014) Abnormalities of the glutamine-glutamate-GABA cycle in the schizophrenia brain. Schizophr Res 156:281–282

    Article  PubMed  Google Scholar 

  9. Ohgi Y, Futamura T, Hashimoto K (2015) Glutamate signaling in synaptogenesis and NMDA receptors as potential therapeutic targets for psychiatric disorders. Curr Mol Med 15:206–221

    Article  CAS  PubMed  Google Scholar 

  10. Machado-Vieira R, Henter ID, Zarate CA Jr (2015) New targets for rapid antidepressant action. Prog Neurobiol 2015 Dec 23. pii:S0301-0082(15)30038-1. doi:10.1016/j.pneurobio.2015.12.001

  11. Ribeiro FM, Vieira LB, Pires RG, Olmo RP, Ferguson SS (2016) Metabotropic glutamate receptors and neurodegenerative diseases. Pharmacol Res 115:179–191

    Article  PubMed  Google Scholar 

  12. Dore K, Aow J, Malinow R (2016) The emergence of NMDA receptor metabotropic function: insights from imaging. Front Synaptic Neurosci 8:20

    Article  PubMed  PubMed Central  Google Scholar 

  13. Alfredsson G, Wiesel FA, Tylec A (1988) Relationships between glutamate and monoamine metabolites in cerebrospinal fluid and serum in healthy volunteers. Biol Psychiatry 23:689–697

    Article  CAS  PubMed  Google Scholar 

  14. O'Kane RL, Viña JR, Simpson I, Hawkins RA (2004) Na+-dependent neutral amino acid transporters A, ASC, and N of the blood-brain barrier: mechanisms for neutral amino acid removal. Am J Physiol Endocrinol Metab 287:E622–E629

    Article  PubMed  Google Scholar 

  15. Hawkins RA, O'Kane RL, Simpson IA, Viña JR (2006) Structure of the blood-brain barrier and its role in the transport of amino acids. J Nutr 136(1 Suppl):218S–226S

    CAS  PubMed  Google Scholar 

  16. Hawkins RA, Viña JR (2016) How glutamate is managed by the blood-brain barrier. Biology (Basel) 5:E37

    Google Scholar 

  17. Fujita Y, Ishima T, Hashimoto K (2016) Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation. Sci Rep 6:37261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Macciardi F, Lucca A, Catalano M, Marino C, Zanardi R, Smeraldi E (1990) Amino acids patterns in schizophrenia: some new findings. Psychiatry Res 32:63–70

    Article  CAS  PubMed  Google Scholar 

  19. Palomino A, González-Pinto A, Aldama A, González-Gómez C, Mosquera F, González-García G, Matute C (2007) Decreased levels of plasma glutamate in patients with first-episode schizophrenia and bipolar disorder. Schizophr Res 95:174–178

    Article  PubMed  Google Scholar 

  20. Tomiya M, Fukushima T, Watanabe H, Fukami G, Fujisaki M, Iyo M, Hashimoto K, Mitsuhashi S, Toyo'oka T (2007) Alterations in serum amino acid concentrations in male and female schizophrenic patients. Clin Chim Acta 380:186–190

    Article  CAS  PubMed  Google Scholar 

  21. Maeshima H, Ohnuma T, Sakai Y, Shibata N, Baba H, Ihara H, Higashi M, Ohkubo T, Nozawa E, Abe S, Ichikawa A, Nakano Y, Utsumi Y, Suzuki T, Arai H (2007) Increased plasma glutamate by antipsychotic medication and its relationship to glutaminase 1 and 2 genotypes in schizophrenia – Juntendo University Schizophrenia Projects (JUSP). Prog Neuro-Psychopharmacol Biol Psychiatry 231:1410–1418

    Article  Google Scholar 

  22. Fukushima T, Iizuka H, Yokota A, Suzuki T, Ohno C, Kono Y, Nishikiori M, Seki A, Ichiba H, Watanabe Y, Hongo S, Utsunomiya M, Nakatani M, Sadamoto K, Yoshio T (2014) Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients. PLoS One 9:e101652

    Article  PubMed  PubMed Central  Google Scholar 

  23. Nishimura Y, Kawakubo Y, Suga M, Hashimoto K, Takei Y, Takei K, Inoue H, Yumoto M, Takizawa R, Kasai K (2016) Familial influences on mismatch negativity and its association with plasma glutamate level: a magnetoencephalographic study in twins. Mol Neuropsychiatry 2:161–172

    Article  CAS  PubMed  Google Scholar 

  24. Hashimoto K, Fukushima T, Shimizu E, Komatsu N, Watanabe H, Shinoda N, Nakazato M, Kumakiri C, Okada S, Hasegawa H, Imai K, Iyo M (2003) 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 60:572–576

    Article  CAS  PubMed  Google Scholar 

  25. Yamada K, Ohnishi T, Hashimoto K, Ohba H, Iwayama-Shigeno Y, Toyoshima M, Okuno A, Takao H, Toyota T, Minabe Y, Nakamura K, Shimizu E, Itokawa M, Mori N, Iyo M, Yoshikawa T (2005) Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels. Biol Psychiatry 57:1493–1503

    Article  CAS  PubMed  Google Scholar 

  26. Calcia MA, Madeira C, Alheira FV, Silva TC, Tannos FM, Vargas-Lopes C, Goldenstein N, Brasil MA, Ferreira ST, Panizzutti R (2012) Plasma levels of D-serine in Brazilian individuals with schizophrenia. Schizophr Res 142:83–87

    Article  PubMed  Google Scholar 

  27. Cho SE, Na KS, Cho SJ, Kang SG (2016) Low D-serine levels in schizophrenia: a systemic review and meta-analysis. Neurosci Lett 634:42–51

    Article  CAS  PubMed  Google Scholar 

  28. Yamamori H, Hashimoto R, Fujita Y, Numata S, Yasuda Y, Fujimoto M, Ohi K, Umeda-Yano S, Ito A, Ohmori T, Hashimoto KM (2014) Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment. Neurosci Lett 582:93–98

    Article  CAS  PubMed  Google Scholar 

  29. Sumiyoshi T, Anil AE, Jin D, Jayathilake K, Lee M, Meltzer HY (2004) Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Int J Neuropsychopharmacol 7:1–8

    Article  CAS  PubMed  Google Scholar 

  30. Kim JS, Kornhuber HH, Holzmüller B, Schmid-Burgk W, Mergner T, Krzepinski G (1980) Reduction of cerebrospinal fluid glutamic acid in Huntigton’s chorea and in schizophrenic patients. Arch Psychiatry Nervenkr 228:7–10

    Article  CAS  Google Scholar 

  31. Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmuller B (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 20:379–382

    Article  CAS  PubMed  Google Scholar 

  32. Perry TL (1982) Normal cerebrospinal fluid and brain glutamate levels in schizophrenia do not support the hypothesis of glutamatergic neuronal dysfunction. Neurosci Lett 28:81–85

    Article  CAS  PubMed  Google Scholar 

  33. Do KQ, Lauer CJ, Schreiber W, Zollinger M, Gutteck-Amsler U, Cuenod M, Holsboer F (1995) γ-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders. J Neurochem 65:2652–2662

    Article  CAS  PubMed  Google Scholar 

  34. Tsai G, van Kammen DP, Chen S, Kelley ME, Grier A, Coyle JT (1998) Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia. Biol Psychiatry 44:667–674

    Article  CAS  PubMed  Google Scholar 

  35. Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindström LH, Iyo M (2005) Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients. BMC Psychiatry 5:6

    Article  PubMed  PubMed Central  Google Scholar 

  36. Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindström LH, Iyo M (2005) Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuro-Psychopharmacol Biol Psychiatry 29:767–769

    Article  CAS  Google Scholar 

  37. Bendikov I, Nadri C, Amar S, Panizzutti R, De Miranda J, Wolosker H, Agam G (2007) A CSF and postmortem brain study of D-serine metabolic parameters in schizophrenia. Schizophr Res 90:41–51

    Article  PubMed  Google Scholar 

  38. Fuchs SA, De Barse MM, Scheepers FE, Cahn W, Dorland L, de Sain-van d, Velden MG, Klomp LW, Berger R, Kahn RS, de Koning TJ (2008) Cerebrospinal fluid D-serine and glycine concentrations are unaltered and unaffected by olanzapine therapy in male schizophrenic patients. Eur Neuropsychopharmacol 18:333–338

    Article  CAS  PubMed  Google Scholar 

  39. Kim JS, Schmid-Burgk W, Claus D, Kornhuber HH (1982) Increased serum glutamate in depressed patients. Arch Psychiatr Nervenkr 232:299–304

    Article  CAS  PubMed  Google Scholar 

  40. Altamura CA, Mauri MC, Ferrara A, Moro AR, D’Andrea G, Zamberian F (1993) Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry 150:1731–1713

    Article  CAS  PubMed  Google Scholar 

  41. Mauri MC, Ferrara A, Boscati L, Bravin S, Zamberlan F, Alecci M, Invernizzi G (1998) Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology 37:124–129

    Article  CAS  PubMed  Google Scholar 

  42. Mitani H, Shirayama Y, Yamada T, Maeda K, Ashby CR Jr, Kawahara R (2006) Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog Neuro-Psychopharmacol Biol Psychiatry 30:1155–1158

    Article  CAS  Google Scholar 

  43. Begni B, Tremolizzo L, D'Orlando C, Bono MS, Garofolo R, Longoni M, Ferrarese C (2005) Substrate-induced modulation of glutamate uptake in human platelets. Br J Pharmacol 145:792–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hoogland G, Bos IW, Kupper F, van Willigen G, Spierenburg HA, van Nieuwenhuizen O, de Graan PN (2005) Thrombin-stimulated glutamate uptake in human platelets is predominantly mediated by the glial glutamate transporter EAAT2. Neurochem Int 47:499–506

    Article  CAS  PubMed  Google Scholar 

  45. Kalev-Zylinska ML, Green TN, Morel-Kopp MC, Sun PP, Park YE, Lasham A, During MJ, Ward CM (2014) N-Methyl-D-aspartate receptors amplify activation and aggregation of human platelets. Thromb Res 133:837–847

    Article  CAS  PubMed  Google Scholar 

  46. Hitchcock IS, Skerry TM, Howard MR, Genever PG (2003) NMDA receptor-mediated regulation of human megakaryocytopoiesis. Blood 102:1254–1259

    Article  CAS  PubMed  Google Scholar 

  47. Berk M, Helene P, Ferreira D (2001) Platelet glutamate receptor supersensitivity in major depressive disorder. Clin Neuropharmacol 24:129–132

    Article  CAS  PubMed  Google Scholar 

  48. Hashimoto K, Yoshida T, Ishikawa M, Fujita Y, Niitsu T, Nakazato M, Watanabe H, Sasaki T, Shiina A, Hashimoto T, Kanahara N, Hasegawa T, Enohara M, Kimura A, Iyo M (2016) Increased serum levels of serine enantiomers in patients with schizophrenia. Acta Neuropsychiatr 28:173–178

    Article  PubMed  Google Scholar 

  49. Pålsson E, Jakobsson J, Södersten K, Fujita Y, Sellgren C, Ekman CJ, Ågren H, Hashimoto KM (2015) Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls. Eur Neuropsychopharmacol 25:133–140

    Article  PubMed  Google Scholar 

  50. Yoshimi N, Futamura T, Kakumoto K, Salehi AM, Sellgren CM, Holmén-Larsson J, Jakobsson J, Pålsson E, Landén M, Hashimoto K (2016) Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder. BBA Clin 5:151–158

    Article  PubMed  PubMed Central  Google Scholar 

  51. Hashimoto K (2016) Serine enantiomers as diagnostic biomarkers for schizophrenia and bipolar disorder. Eur Arch Psychiatry Clin Neurosci 266:83–85

    Article  PubMed  Google Scholar 

  52. Levine J, Panchalingam K, Rapoport A, Gershon S, McClure RJ, Pettegrew JW (2000) Increased cerebrospinal fluid glutamine levels in depressed patients. Biol Psychiatry 47:586–593

    Article  CAS  PubMed  Google Scholar 

  53. Frye MA, Tsai GE, Huggins T, Coyle JT, Post RM (2007) Low cerebrospinal fluid glutamate and glycine in refractory affective disorder. Biol Psychiatry 61:162–166

    Article  CAS  PubMed  Google Scholar 

  54. Garakani A, Martinez JM, Yehuda R, Gorman JM (2013) Cerebrospinal fluid levels of glutamate and corticotropin releasing hormone in major depression before and after treatment. J Affect Disord 146:262–265

    Article  CAS  PubMed  Google Scholar 

  55. Hashimoto K, Bruno D, Nierenberg J, Marmar CR, Zetterberg H, Blennow K, Pomara N (2016) Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study. Transl Psychiatry 6:e744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gerner RH, Fairbanks L, Anderson GM, Young JG, Scheinin M, Linnoila M, Hare TA, Shaywitz BA, Cohen DJ (1984) CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. Am J Psychiatry 141:1533–1540

    Article  CAS  PubMed  Google Scholar 

  57. Vieira DS, Naffah-Mazacoratti MG, Zukerman E, Senne Soares CA, Alonso EO, Faulhaber MH, Cavalheiro EA, Peres MF (2006) Cerebrospinal fluid GABA levels in chronic migraine with and without depression. Brain Res 1090:197–201

    Article  CAS  PubMed  Google Scholar 

  58. Mann JJ, Oquendo MA, Watson KT, Boldrini M, Malone KM, Ellis SP, Sullivan G, Cooper TB, Xie S, Currier D (2014) Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid. Depress Anxiety 31:814–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148:1301–1308

    Article  CAS  PubMed  Google Scholar 

  60. Olney JW, Farber NB (1995) Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 52:998–1007

    Article  CAS  PubMed  Google Scholar 

  61. Coyle JT (1996) The glutamatergic dysfunction hypothesis for schizophrenia. Harv Rev Psychiatry 3:241–253

    Article  CAS  PubMed  Google Scholar 

  62. Krystal JH, D'Souza DC, Petrakis IL, Belger A, Berman RM, Charney DS, Abi-Saab W, Madonick S (1999) NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders. Harv Rev Psychiatry 7:125–143

    Article  CAS  PubMed  Google Scholar 

  63. Hashimoto K, Okamura N, Shimizu E, Iyo M (2004) Glutamate hypothesis of schizophrenia and approach for possible therapeutic drugs. Curr Med Chem CNS Agents 4:147–154

    CAS  Google Scholar 

  64. Hashimoto K, Shimizu E, Iyo M (2005) Dysfunction of glia-neuron communication in pathophysiology of schizophrenia. Curr Psychiatr Rev 1:151–163

    Article  CAS  Google Scholar 

  65. Tsai G, Lin PY (2010) Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis. Curr Pharm Des 16:522–537

    Article  CAS  PubMed  Google Scholar 

  66. Singh SP, Singh V (2011) Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs 25:859–885

    Article  CAS  PubMed  Google Scholar 

  67. Sanacora G, Zarate CA, Krystal JH, Manji HK (2008) Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 7:426–437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Krystal JH, Sanacorra G, Duman RS (2013) Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry 73:1133–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dang YH, Ma XC, Zhang JC, Ren Q, Wu J, Gao CG, Hashimoto K (2014) Targeting of NMDA receptors in the treatment of major depression. Curr Pharm Des 20:5151–5159

    Article  CAS  PubMed  Google Scholar 

  70. Monteggia LM, Zarate C Jr (2015) Antidepressant actions of ketamine: from molecular mechanisms to clinical practice. Curr Opin Neurobiol 30:13–143

    Article  Google Scholar 

  71. Hashimoto K, Sawa A, Iyo M (2007) Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 62:1310–1316

    Article  CAS  PubMed  Google Scholar 

  72. Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF (2004) Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 61:705–713

    Article  CAS  PubMed  Google Scholar 

  73. Auer DP, Pütz B, Kraft E, Lipinski B, Schill J, Holsboer F (2000) Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 47:305–313

    Article  CAS  PubMed  Google Scholar 

  74. Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC (2007) Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 64:193–200

    Article  CAS  PubMed  Google Scholar 

  75. Godlewska BR, Near J, Cowen PJ (2015) Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology 232:501–507

    Article  CAS  PubMed  Google Scholar 

  76. Hermens DF, Naismith SL, Chitty KM, Lee RS, Tickell A, Duffy SL, Paquola C, White D, Hickie IB, Lagopoulos J (2015) Cluster analysis reveals abnormal hippocampal neurometabolic profiles in young people with mood disorders. Eur Neuropsychopharmacol 25:836–845

    Article  CAS  PubMed  Google Scholar 

  77. Arnone D, Mumuni AN, Jauhar S, Condon B, Cavanagh J (2015) Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol 25:1109–1117

    Article  CAS  PubMed  Google Scholar 

  78. Shirayama Y, Takahashi M, Osone F, Hara A, Okubo T (2017) Myo-inositol, glutamate and glutamine in the prefrontal cortex, hippocampus and amygdala in major depression. Biol Psychiatry Cog Neurosci Neuroimaging 2:196–204

    Google Scholar 

  79. Jeon JP, Yun T, Jin X, Cho WS, Son YJ, Bang JS, Kang HS, Oh CW, Kim JE, Park S (2015) 1H-NMR-based metabolomic analysis of cerebrospinal fluid from adult bilateral moyamoya disease: comparison with unilateral moyamoya disease and atherosclerotic stenosis. Medicine (Baltimore) 94:e629

    Article  CAS  Google Scholar 

  80. Kashiwagi Y, Kawashima H, Suzuki S, Nishimata S, Takekuma K, Hoshika A (2015) Marked elevation of excitatory amino acids in cerebrospinal fluid obtained from patients with rotavirus-associated encephalopathy. J Clin Lab Anal 29:328–333

    Article  CAS  PubMed  Google Scholar 

  81. Camargo JA, Bertolucci PH (2015) Quantification of amino acid neurotransmitters in cerebrospinal fluid of patients with neurocysticercosis. Open Neurol J 9:15–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. van Dongen RM, Zielman R, Noga M, Dekkers OM, Hankemeier T, van den Maagdenberg AM, Terwindt GM, Ferrari MD (2016) Migraine biomarkers in cerebrospinal fluid: a systematic review and meta-analysis. Cephalagia 37:49–63

    Article  Google Scholar 

  83. Madeira C, Lourenco MV, Vargas-Lopes C, Suemoto CK, Brandão CO, Reis T, Leite RE, Laks J, Jacob-Filho W, Pasqualucci CA, Grinberg LT, Ferreira ST, Panizzutti R (2015) D-serine levels in Alzheimer’s disease: implications for novel biomarker development. Transl Psychiatry 5:e561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Biemans EA, Verhoeven-Duif NM, Gerrits J, Claassen JA, Kuiperij HB, Verbeek MM (2016) CSF D-serine concentrations are similar in Alzheimer’s disease, other dementias, and elderly controls. Neurobiol Aging 42:213–216

    Article  CAS  PubMed  Google Scholar 

  85. Weiss N, Barbier Saint Hilaire P, Colsch B, Isnard F, Attala S, Schaefer A, Amador MD, Rudler M, Lamari F, Sedel F, Thabut D, Junot C (2016) Cerebrospinal fluid metabolomics highlights dysregulation of energy metabolism in overt hepatic encephalopathy. J Hepatol 65:1120–1130

    Article  CAS  PubMed  Google Scholar 

  86. Cassol E, Misra V, Dutta A, Morgello S, Gabuzda D (2014) Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment. AIDS 28:1579–1591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Aoyama C, Santa T, Tsunoda M, Fukushima T, Kitada C, Imai K (2004) A fully automated amino acid analyzer using NBD-F as a fluorescent derivatization reagent. Biomed Chromatogr 18:630–636

    Article  CAS  PubMed  Google Scholar 

  88. Eckstein JA, Ammerman GM, Reveles JM, Ackermann BL (2008) Analysis of glutamine, glutamate, pyroglutamate, and GABA in cerebrospinal fluid using ion pairing HPLC with positive electrospray LC/MS/MS. J Neurosci Methods 171:190–196

    Article  CAS  PubMed  Google Scholar 

  89. Hamase K, Morikawa A, Zaitsu K (2002) D-Amino acids in mammals and their diagnostic value. J Chromatogr B Analyt Technol Biomed Life Sci 781:73–91

    Article  CAS  PubMed  Google Scholar 

  90. Hamase K, Konno R, Morikawa A, Zaitsu K (2006) Sensitive determination of D-amino acids in mammals and the effect of D-amino acid oxidase activity on their amounts. Biol Pharm Bull 28:1578–1584

    Article  Google Scholar 

  91. Fukushima T, Kawai J, Imai K, Toyo’oka T (2004) Simultaneous determination of D- and L-serine in rat brain microdialysis sample using a column-switching HPLC with fluorimetric detection. Biomed Chromatogr 18:813–819

    Article  CAS  PubMed  Google Scholar 

  92. Koval D, Jiraskova J, Strisovsky, Konvalinka J, Kasicka V (2006) Capillary electrophoresis method for determination of D-serine and its application for monitoring of serine racemase activity. Electrophoresis 27:2558–2566

    Article  CAS  PubMed  Google Scholar 

  93. Kayser MS, Dalmau J (2016) Anti-NMDA receptor encephalitis, autoimmunity, and psychosis. Schizophr Res 176:36–40

    Article  PubMed  Google Scholar 

  94. Barry H, Byrne S, Barrett E, Murphy KC, Cotter DR (2015) Anti-N-methyl-D-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bull 39:19–23

    Article  PubMed  PubMed Central  Google Scholar 

  95. Kiani R, Lawden M, Eames P, Critchley P, Bhaumik S, Odedra S, Gumber R (2015) Anti-NMDA-receptor encephalitis presenting with catatonia and neuroleptic malignant syndrome in patients with intellectual disability and autism. BJPsych Bull 39:32–35

    Article  PubMed  PubMed Central  Google Scholar 

  96. Dalmau J (2016) NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: the 2016 Cotzias Lecture. Neurology 87:2471–2482

    Article  CAS  PubMed  Google Scholar 

  97. Hogan-Cann AD, Anderson CM (2016) Physiological roles of non-neuronal NMDA receptors. Trends Pharmacol Sci 37:750–767

    Article  CAS  PubMed  Google Scholar 

  98. Julio-Pieper M, Flor PJ, Dinan TG, Cryan JF (2011) Exciting times beyond the brain: metabotropic glutamate receptors in peripheral and non-neural tissues. Pharmacol Rev 63:35–58

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research on Innovative Areas of the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Strategic Research Program for Brain Sciences, from Japan Agency for Medical Research and Development, AMED.

Author information

Authors and Affiliations

  1. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba, 260-8670, Japan

    Kenji Hashimoto

Authors
  1. Kenji Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenji Hashimoto .

Editor information

Editors and Affiliations

  1. Lyon Neuroscience Research Center, University Lyon 1, Lyon, France

    Sandrine Parrot

  2. Lyon Neuroscience Research Center, University Lyon 1, Lyon, France

    Luc Denoroy

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Hashimoto, K. (2018). The Glutamatergic System as Potential Clinical Biomarkers for Blood and Cerebrospinal Fluid Monitoring. In: Parrot, S., Denoroy, L. (eds) Biochemical Approaches for Glutamatergic Neurotransmission. Neuromethods, vol 130. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7228-9_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7228-9_16

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7227-2

  • Online ISBN: 978-1-4939-7228-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation