Central N-acetyl aspartylglutamate deficit: A possible pathogenesis of schizophrenia

Medical Science Monitor

Volumn 11, Issue 9, 2005, Pages

  Tsai, Shih Jen ^a,b  

^a TAIPEI VETERANS GENERAL HOSPITAL   (Taiwan)

^b NATIONAL YANG MING UNIVERSITY   (Taiwan)

Author keywords

Glutamate; Glutamate carboxypeptidase II; N acetyl aspartylglutamate; N acetylaspartate; N methyl D aspartate receptor; Schizophrenia; Type 3 metabotropic glutamate receptor

Indexed keywords

GLUTAMIC ACID; METABOTROPIC RECEPTOR 3; N ACETYLASPARTIC ACID; N ACETYLASPARTYLGLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEUROTRANSMITTER; PHENCYCLIDINE;

AUTOPSY; BRAIN CELL; BRAIN METABOLISM; HIPPOCAMPUS; NEUROTRANSMISSION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PYRAMIDAL NERVE CELL; REVIEW; SCHIZOPHRENIA;

ANIMALS; ASPARTIC ACID; BRAIN; DIPEPTIDES; GLUTAMIC ACID; HUMANS; MODELS, NEUROLOGICAL; RECEPTORS, N-METHYL-D-ASPARTATE; SCHIZOPHRENIA;

EID: 24944566294     PISSN: 12341010     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (83)

1. Luby ED, Cohen BD, Rosenbaum G et al: Study of a new schizophrenomimetic drug: sernyl. AMA Arch Neurol Psychiatry, 1959; 81: 363-69
2. 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
3. Olney JW, Newcomer JW, Farber NB: NMDA receptor hypofunction model of schizophrenia. J Psychiatr Res, 1999; 33: 523-33
4. Kilbride J, Huang LQ, Rowan MJ, Anwyl R: Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV. Eur J Pharmacol, 1998; 356: 149-57
5. Schoepp DD, Jane DE, Monn JA: Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology, 1999; 38: 1431-76
6. Sawa A, Snyder SH: Schizophrenia: neural mechanisms for novel therapies. Mol Med, 2003; 9: 3-9
7. Konradi C, Heckers S: Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacol Ther, 2003; 97: 153-79
8. Moghaddam B, Adams BW: Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science, 1998; 281: 1349-52
9. Cartmell J, Monn JA, Schoepp DD: The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats. J Pharmacol Exp Ther, 1999; 291: 161-70
10. Okamura N, Hashimoto K, Shimizu E et al: Protective effect of LY379268, a selective group II metabotropic glutamate receptor agonist, on dizocilpine-induced neuropathological changes in rat retrosplenial cortex. Brain Res, 2003; 992: 114-19
11. Krystal JH, Abi-Saab W, Perry E et al: Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology, (in press)
12. Chavez-Noriega LE, Schaffhauser H, Campbell UC: Metabotropic glutamate receptors: potential drug targets for the treatment of schizophrenia. Curr Drug Targets CNS Neurol Disord, 2002; 1: 261-81
13. Schoepp DD, Marek GJ: Preclinical pharmacology of mGlu2/3 receptor agonists: novel agents for schizophrenia? Curr Drug Targets CNS Neurol Disord, 2002; 1: 215-25
14. Coyle JT, Tsai G: The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. Psychopharmacology, 2004; 174: 32-38
15. Tyson RL, Sutherland GR: Labeling of N-acetylaspartate and N-acetylaspartylglutamate in rat neocortex, hippocampus and cerebellum from [1-13C]glucose. Neurosci Lett, 1998; 251: 181-84
16. Gehl LM, Saab OH, Bzdega T et al: Biosynthesis of NAAG by an enzyme-mediated process in rat central nervous system neurons and glia. J Neurochem, 2004; 90: 989-97
17. Tsai G, Coyle JT: N-Acetylaspartate in neuropsychiatric disorder's. Prog Neurobiol, 1995; 46: 531-40
18. Westbrook GL, Mayer ML, Namboodiri MA, Neale JH: High concentrations of N-acetylaspartylglutamate (NAAG) selectively activate NMDA receptors on mouse spinal cord neurons in cell culture. J Neurosci, 1986; 6: 3385-92
19. Wroblewska B, Wroblewski JT, Saab OH, Neale JH: N-acetylaspartylglutamate inhibits forskolin-stimulated cyclic AMP levels via a metabotropic glutamate receptor in cultured cerebellar granule cells. J Neurochem, 1993; 61: 943-48
20. Wroblewska B, Wroblewski JT, Pshenichkin S et al: N- acetylaspartylglutamate selectively activates mGluR3 receptors in transfected cells. J Neurochem, 1997; 69: 174-81
21. Bruno V, Wroblewska B, Wroblewski JT et al: Neuroprotective activity of N-acetylaspartylglutamate in cultured cortical cells. Neuroscience, 1998; 85: 751-57
22. Baslow MH: N-acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res, 2003; 28: 941-53
23. Fukuzako H, Takeuchi K, Hokazono Y et al: Proton magnetic resonance spectroscopy of the left medial temporal and frontal lobes in chronic schizophrenia: preliminary report. Psychiatry Res, 1995; 61: 193-200
24. Stanley JA, Drost DJ, Williamson PC, Thompson RT: The use of a priori knowledge to quantify short echo in vivo 1H MR spectra. Magn Reson Med, 1995; 34: 17-24
25. Stanley JA, Pettegrew JW, Keshavan MS: Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings - part 1. Biol Psychiatry, 2000; 48: 357-68
26. Deicken RF, Johnson C, Pegues M: Proton magnetic resonance spectroscopy of the human brain in schizophrenia. Rev Neurosci, 2000; 11: 147-58
27. Harrison PJ, Weinberger DR: Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry, 2005; 10: 40-68
28. Sigmundsson T, Maier M, Toone BK et al: Frontal lobe N-acetylaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res, 2003; 64: 63-71
29. Callicott JH, Bertolino A, Egan MF et al: Selective relationship between prefrontal N-acetylaspartate measures and negative symptoms in schizophrenia. Am J Psychiatry, 2000; 157: 1646-51
30. Demougeot C, Garier P, Mossiat C et al: N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury. J Neurochem, 2001; 77: 408-15
31. Deicken RF, Pegues M, Amend D: Reduced hippocampal N-acetylaspartate without volume loss in schizophrenia. Schizophr Res, 1999; 37: 217-23
32. Nudmamud S, Reynolds LM, Reynolds GP: N-acetylaspartate and N-Acetylaspartylglutamate deficits in superior temporal cortex in schizophrenia and bipolar disorder: a postmortem study. Biol Psychiatry, 2003; 53: 1138-41
33. Tsai G, Passani LA, Slusher BS et al: Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Arch Gen Psychiatry, 1995; 52: 829-36
34. Schweinsburg BC, Taylor MJ, Alhassoon OM et al: Chemical pathology in brain white matter of recently detoxified alcoholics: a 1H magnetic resonance spectroscopy investigation of alcohol-associated frontal lobe injury. Alcohol Clin Exp Res, 2001; 25: 924-34
35. Govindaraju V, Ganger GE, Manley GT et al: Volumetric proton spectroscopic imaging of mild traumatic brain injury. AJNR Am J Neuroradiol, 2004; 25: 730-37
36. Reynolds LM, Cochran SM, Morris BJ et al: Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain. Schizophr Res, 2005; 73: 147-52
37. Harte MK, Powell SB, Reynolds LM et al: Reduced N-acetylaspartate in the temporal cortex of rats reared in isolation. Biol Psychiatry, 2004; 56: 296-99
38. Bertolino A, Roffman JL, Lipska BK et al: Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage. Cereb Cortex, 2002; 12: 983-90
39. Ende G, Braus DF, Walter S et al: Effects of age, medication, and illness duration on the N-acetyl aspartate signal of the anterior cingulate region in schizophrenia. Schizophr Res, 2000; 41: 389-95
40. Braus DF, Ende G, Weber-Fahr W et al: Favorable effect on neuronal viability in the anterior cingulate gyrus due to long-term treatment with atypical antipsychotics: an MRSI study. Pharmacopsychiatry, 2001; 34: 251-53
41. Bertolino A, Callicott JH, Mattay VS et al: The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia. Biol Psychiatry, 2001; 49: 39-46
42. Meyerhoff JL, Koller KJ, Walczak DD, Coyle JT: Regional brain levels of N-acetyl-aspartyl-glutamate: the effect of kindled seizures. Brain Res, 1985; 346: 392-96
43. Meyerhoff JL, Robinson MB, Bixler MA et al: Seizures decrease regional enzymatic hydrolysis of N-acetyl-aspartylglutamate in rat brain. Brain Res, 1989; 505: 130-34
44. Michael N, Erfurth A, Ohrmann P et al: Neurotrophic effects of electroconvulsive therapy: a proton magnetic resonance study of the left amygdalar region in patients with treatment-resistant depression. Neuropsychopharmacology, 2003; 28: 720-25
45. Kodsi MH, Swerdlow NR: Mitochondrial toxin 3-nitropropionic acid produces startle reflex abnormalities and striatal damage in rats that model some features of Huntington's disease. Neurosci Lett, 1997; 231: 103-7
46. Ben-Shachar D: Mitochondrial dysfunction in schizophrenia: a possible linkage to dopamine. J Neurochem, 2002; 83: 1241-51
47. Stauch BL, Robinson MB, Forloni G et al: The effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on [3H]NAAG catabolism in vivo. Neurosci Lett, 1989; 100: 295-300
48. Ghose S, Weickert CS, Colvin SM et al: Glutamate carboxypeptidase II gene expression in the human frontal and temporal lobe in schizophrenia. Neuropsychopharmacology, 2004; 29: 117-25
49. Olszewski RT, Bukhari N, Zhou J et al: NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR. J Neurochem, 2004; 89: 876-85
50. Flores C, Coyle JT: Regulation of glutamate carboxypeptidase II function in corticolimbic regions of rat brain by phencyclidine, haloperidol, and clozapine. Neuropsychopharmacology, 2003; 28: 1227-34
51. Coyle JT: The nagging question of the function of N- acetylaspartylglutamate. Neurobiol Dis, 1997; 4: 231-38
52. Farber NB, Wozniak DF, Price MT et al: Age-specific neurotoxicity in the rat associated with NMDA receptor blockade: potential relevance to schizophrenia? Biol Psychiatry, 1995; 38: 788-96
53. Thomas AG, Vornov JJ, Olkowski JL et al: N-Acetylated alpha-linked acidic dipeptidase converts N-acetylaspartylglutamate from a neuroprotectant to a neurotoxin. J Pharmacol Exp Ther, 2000; 295: 16-22
54. Slusher BS, Vornov JJ, Thomas AG et al: Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat Med, 1999; 5: 1396-402
55. Tsuang M: Schizophrenia: genes and environment. Biol Psychiatry, 2000; 47: 210-20
56. Ho BC, Andreasen NC, Nopoulos P et al: Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiatry, 2003; 60: 585-94
57. Poland RE, Cloak C, Lutchmansingh PJ et al: Brain N-acetyl aspartate concentrations measured by H MRS are reduced in adult male rats subjected to perinatal stress: preliminary observations and hypothetical implications for neurodevelopmental disorders. J Psychiatr Res, 1999; 33: 41-51
58. Middleton FA, Mirnics K, Pierri JN et al: Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia. J Neurosci, 2002; 22: 2718-29
59. Bertolino A, Callicott JH, Elman I et al: Regionally specific neuronal pathology in untreated patients with schizophrenia: a proton magnetic resonance spectroscopic imaging study. Biol Psychiatry, 1998; 43: 641-48
60. Brooks WM, Hodde-Vargas J, Vargas LA et al: Frontal lobe of children with schizophrenia spectrum disorders: a proton magnetic resonance spectroscopic study. Biol Psychiatry, 1998; 43: 263-69
61. Callicott JH, Egan MF, Bertolino A et al: Hippocampal N-acetyl aspartate in unaffected siblings of patients with schizophrenia: a possible intermediate neurobiological phenotype. Biol Psychiatry, 1998; 44: 941-50
62. Mathew SJ, Shungu DC, Mao X et al: A magnetic resonance spectroscopic imaging study of adult nonhuman primates exposed to early-life Stressors. Biol Psychiatry, 2003; 54: 727-35
63. Ohrmann P, Siegmund A, Suslow T et al: Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res, 2005; 73: 153-57
64. Molina V, Sanchez J, Reig S et al: N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration. Schizophr Res, 2005; 73: 209-19
65. Tsai SJ: Strategies to increase central N-acetyl aspartylglutamate: A potential treatment for schizophrenia and bipolar disorders. Schizophr Res, 2005; 76: 359-60
66. Heimberg C, Komoroski RA, Lawson WB et al: Regional proton magnetic resonance spectroscopy in schizophrenia and exploration of drug effect. Psychiatry Res, 1998; 83: 105-15
67. Clark JB: N-acetyl aspartate: a marker for neuronal loss or mitochondrial dysfunction. Dev Neurosci, 1998; 20: 271-76
68. Black K, Peters L, Rui Q et al: Duration of untreated psychosis predicts treatment outcome in an early psychosis program. Schizophr Res, 2001; 47: 215-22
69. Haas GL, Garratt LS, Sweeney JA: Delay to first antipsychotic medication in schizophrenia: impact on symptomatology and clinical course of illness. J Psychiatr Res, 1998; 32: 151-59
70. Keshavan MS, Haas G, Miewald J et al: Prolonged untreated illness duration from prodromal onset predicts outcome in first episode psychoses. Schizophr Bull, 2003; 29: 757-69
71. Moreno A, Ross BD, Bluml S: Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by (13) C MRS and [1-(13)C]glucose infusion. J Neurochem, 2001; 77: 347-50
72. Miyake M, Kakimoto Y, Sorimachi M: A gas Chromatographic method for the determination of N-acetyl-L-aspartic acid, N-acetyl-alpha-aspartylglutamic acid and beta-citryl-L-glutamic acid and their distributions in the brain and other organs of various species of animals. J Neurochem, 1981; 36: 804-10
73. Jakobs C, ten Brink HJ, Langelaar SA et al: Stable isotope dilution analysis of N-acetylaspartic acid in CSF, blood, urine and amniotic fluid: accurate postnatal diagnosis and the potential for prenatal diagnosis of Canavan disease. J Inherit Metab Dis, 1991; 14: 653-60
74. Miyake M, Morino H, Mizobuchi M, Kakimoto Y: N-acetyl-L-aspartic acid, N-acetyl-alpha-L-aspartyl-L-glutamic acid and beta-citryl-L-glutamic acid in human urine. Clin Chim Acta, 1982; 120: 119-26
75. Cummings JL: Organic psychosis. Psychosomatics, 1988; 29: 16-26
76. Lautenschlager NT, Forstl H: Organic psychosis: Insight into the biology of psychosis. Curr Psychiatry Rep, 2001; 3: 319-25
77. Arciniegas DB, Harris SN, Brousseau KM: Psychosis following traumatic brain injury. Int Rev Psychiatry, 2003; 15: 328-40
78. MacKay S, Ezekiel F, Di Sclafani V et al: Alzheimer disease and subcortical ischemic vascular dementia: evaluation by combining MR imaging segmentation and H-1 MR spectroscopic imaging. Radiology, 1996; 198: 537-45
79. Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR: Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology, 1993; 43: 2689-95
80. Deicken RF, Pegues MP, Anzalone S et al: Lower concentration of hippocampal N-acetylaspartate in familial bipolar I disorder. Am J Psychiatry, 2003; 160: 873-82
81. Ernst T, Chang L, Leonido-Yee M, Speck O: Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study. Neurology, 2000; 54: 1344-49
82. Reneman L, Majoie CB, Flick H, den Heeten GJ: Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (Ecstasy) users: preliminary results. AJNR Am J Neuroradiol, 2002; 23: 231-37
83. Passani LA, Vonsattel JP, Carter RE, Coyle JT: N-acetylaspartylglutamate, N-acetylaspartate, and N-acetylated alpha-linked acidic dipeptidase in human brain and their alterations in Huntington and Alzheimer's diseases. Mol Chem Neuropathol, 1997; 31: 97-118