d ‐Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia

Abstract

The N ‐methyl‐ d ‐aspartate receptor co‐agonist d ‐serine is synthesized by serine racemase and degraded by d ‐amino acid oxidase. Both d ‐serine and its metabolizing enzymes are implicated in N ‐methyl‐ d ‐aspartate receptor hypofunction thought to occur in schizophrenia. We studied d ‐amino acid oxidase and serine racemase immunohistochemically in several brain regions and compared their immunoreactivity and their mRNA levels in the cerebellum and dorsolateral prefrontal cortex in schizophrenia. d ‐Amino acid oxidase immunoreactivity was abundant in glia, especially Bergmann glia, of the cerebellum, whereas in prefrontal cortex, hippocampus and substantia nigra, it was predominantly neuronal. Serine racemase was principally glial in all regions examined and demonstrated prominent white matter staining. In schizophrenia, d ‐amino acid oxidase mRNA was increased in the cerebellum, and as a trend for protein. Serine racemase was increased in schizophrenia in the dorsolateral prefrontal cortex but not in cerebellum, while serine racemase mRNA was unchanged in both regions. Administration of haloperidol to rats did not significantly affect serine racemase or d ‐amino acid oxidase levels. These findings establish the major cell types wherein serine racemase and d ‐amino acid oxidase are expressed in human brain and provide some support for aberrant d ‐serine metabolism in schizophrenia. However, they raise further questions as to the roles of d ‐amino acid oxidase and serine racemase in both physiological and pathophysiological processes in the brain.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 87

1. 1.

   Andreasen NC, Paradiso S, O'Leary DS. ‘Cognitive dysmetria’ as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr. Bull. 1998;24:203-218.

   Not in our library10.1093/oxfordjournals.schbul.a033321

2. 2.

   Arnold G, Liscum L, Holtzman E. Ultrastructural localization of d-amino acid oxidase in microperoxisomes of the rat nervous system. J. Histochem. Cytochem. 1979;27:735-745.

   Not in our library10.1177/27.3.39097

3. 3.

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

   Not in our library10.1016/j.schres.2006.10.010

4. 4.

   Brannan T, Prikhojan A, Yahr MD. Elevated striatal dopamine levels following administration of D-DOPA and its alpha-keto acid metabolite DHPPA: behavioral and physiological studies in vivo in the rat. Brain Res. 1996;718:165-168.

   Not in our library10.1016/0006-8993(96)00116-3

5. 5.

   Brockhaus J, Deitmer JW. Long-lasting modulation of synaptic input to. Purkinje neurons by Bergmann glia stimulation in rat brain slices. J. Physiol. 2002;545:581-593.

   Not in our library10.1113/jphysiol.2002.028423

6. 6.

   Burnet PW, Michelson D, Smith MA, Gold PW, Sternberg EM. The effect of chronic imipramine administration on the densities of 5-HT1A and 5-HT2 receptors and the abundances of 5-HT receptor and transporter mRNA in the cortex, hippocampus and dorsal raphe of three strains of rat. Brain. Res. 1994;638:311-324.

   Not in our library10.1016/0006-8993(94)90664-5

7. 7.

   Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, Puech A, Tahri N, Cohen-Akenine A, Delabrosse S, Lissarrague S, Picard FP, Maurice K, Essioux L, Millasseau P, Grel P, Debailleul V, Simon AM, Caterina D, Dufaure I, Malekzadeh K, Belova M, Luan JJ, Bouillot M, Sambucy JL, Primas G, Saumier M, Boubkiri N, Martin-Saumier S, Nasroune M, Peixoto H, Delaye A, Pinchot V, Bastucci M, Guillou S, Chevillon M, Sainz-Fuertes R, Meguenni S, Aurich-Costa J, Cherif D, Gimalac A, Van Duijn C, Gauvreau D, Ouellette G, Fortier I, Raelson J, Sherbatich T, Riazanskaia N, Rogaev E, Raeymaekers P, Aerssens J, Konings F, Luyten W, Macciardi F, Sham PC, Straub RE, Weinberger DR, Cohen N, Cohen D. Genetic and physiological data implicating the new human gene G72 and the gene for d-amino acid oxidase in schizophrenia. Proc. Natl. Acad. Sci. USA. 2002;99:13675-13680.

   Not in our library10.1073/pnas.182412499

8. 8.

   Cid ME, Ortega A. Glutamate stimulates [3H]phorbol 12,13-dibutyrate binding in cultured Bergmann glia cells. Eur. J. Pharmacol. 1993;245:51-54.

   Not in our library10.1016/0922-4106(93)90168-9

9. 9.

   Corvin A, McGhee KA, Murphy K, Donohoe G, Nangle JM, Schwaiger S, Kenny N, Clarke S, Meagher D, Quinn J, Scully P, Baldwin P, Browne D, Walsh C, Waddington JL, Morris DW, Gill M. Evidence for association and epistasis at the DAOA/G30 and d-amino acid oxidase loci in an Irish schizophrenia sample. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007.

   Not in our library10.1002/ajmg.b.30452

10. 10.

    Coyle JT. The glutamatergic dysfunction hypothesis for schizophrenia. Harv. Rev. Psychiatry. 1996;3:241-253.

    Not in our library10.3109/10673229609017192

11. 11.

    De Miranda J, Santoro A, Engelender S, Wolosker H. Human serine racemase: moleular cloning, genomic organization and functional analysis. Gene. 2000;256:183-188.

    Not in our library10.1016/s0378-1119(00)00356-5

12. 12.

    Detera-Wadleigh SD, McMahon FJ. G72/G30 in schizophrenia and bipolar disorder: review and meta-analysis. Biol. Psychiatry. 2006;60:106-114.

    Not in our library10.1016/j.biopsych.2006.01.019

13. 13.

    Dumin E, Bendikov I, Foltyn VN, Misumi Y, Ikehara Y, Kartvelishvily E, Wolosker H. Modulation of d-serine levels via ubiquitin-dependent proteasomal degradation of serine racemase. J. Biol. Chem. 2006;281:20291-20302.

    Not in our library10.1074/jbc.m601971200

14. 14.

    Eastwood SL, Burnet PW, Gittins R, Baker K, Harrison PJ. Expression of serotonin 5-HT2A receptors in the human cerebellum and alterations in schizophrenia. Synapse. 2001a;42:104-114.

    Not in our library10.1002/syn.1106

15. 15.

    Eastwood SL, Cairns NJ, Harrison PJ. Synaptophysin gene expression in schizophrenia. Investigation of synaptic pathology in the cerebral cortex. Br. J. Psychiatry. 2000;176:236-242.

    Not in our library10.1192/bjp.176.3.236

16. 16.

    Eastwood SL, Cotter D, Harrison PJ. Cerebellar synaptic protein expression in schizophrenia. Neuroscience. 2001b;105:219-229.

    Not in our library10.1016/s0306-4522(01)00141-5

17. 17.

    Eastwood SL, Law AJ, Everall IP, Harrison PJ. The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology. Mol. Psychiatry. 2003;8:148-155.

    Not in our library10.1038/sj.mp.4001233

18. 18.

    Foltyn VN, Bendikov I, De Miranda J, Panizzutti R, Dumin E, Shleper M, Li P, Toney MD, Kartvelishvily E, Wolosker H. Serine racemase modulates intracellular d-serine levels through an alpha,beta-elimination activity. J. Biol. Chem. 2005;280:1754-1763.

    Not in our library10.1074/jbc.m405726200

19. 19.

    Gavazzi E, Malgaretti N, Curti B. Immunochemical properties of d-amino- acid oxidase. Biochim. Biophys. Acta. 1987;915:188-198.

    Not in our library10.1016/0167-4838(87)90299-8

20. 20.

    Goltsov AY, Loseva JG, Andreeva TV, Grigorenko AP, Abramova LI, Kaleda VG, Orlova VA, Moliaka YK, Rogaev EI. Polymorphism in the 5′-promoter region of serine racemase gene in schizophrenia. Mol. Psychiatry. 2006;11:325-326.

    Not in our library10.1038/sj.mp.4001801

21. 21.

    Hamase K, Homma H, Takigawa Y, Fukushima T, Santa T, Imai K. Regional distribution and postnatal changes of d-amino acids in rat brain. Biochem. Biophys. Acta. 1997;1334:214-222.

    Not in our library10.1016/s0304-4165(96)00095-5

22. 22.

    Harrison PJ, Owen MJ. Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet. 2003;361:417-419.

    Not in our library10.1016/s0140-6736(03)12379-3

23. 23.

    Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatry. 2005;10:40-68.

    Not in our library10.1038/sj.mp.4001558

24. 24.

    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;955:214-220.

    Not in our library10.1016/s0006-8993(02)03466-2

25. 25.

    Hashimoto K, Fukushima T, Shimizu E, Komatsu N, Watanabe H, Shinoda N, Nakazato M, Kumakiri C, Okada S, Hasegawa H, Imai K, Iyo M. 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;60:572-576.

    Not in our library10.1001/archpsyc.60.6.572

26. 26.

    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;29:767-769.

    Not in our library10.1016/j.pnpbp.2005.04.023

27. 27.

    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. 1995a;7:1657-1663.

    Not in our library10.1111/j.1460-9568.1995.tb00687.x

28. 28.

    Hashimoto A, Oka T, Nishikawa T. Extracellular concentration of endogenous free d-serine in the rat brain as revealed by in vivo microdialysis. Neuroscience. 1995b;66:635-643.

    Not in our library10.1016/0306-4522(94)00597-x

29. 29.

    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;18:2227-2238.

    Not in our library10.1046/j.1460-9568.2003.02966.x

30. 30.

    Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, Catinari S, Ermilov M. d-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol. Psychiatry. 2005;57:577-585.

    Not in our library10.1016/j.biopsych.2004.12.037

31. 31.

    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.

    Not in our library10.1016/0006-8993(94)90240-2

32. 32.

    Horiike K, Tojo H, Arai R, Yamano T, Nozaki M, Maeda T. Localization of d-amino acid oxidase in Bergmann glial cells and astrocytes of rat cerebellum. Brain Res. Bull. 1987;19:587-596.

    Not in our library10.1016/0361-9230(87)90076-1

33. 33.

    Huang H, Bordey A. Glial glutamate transporters limit spillover activation of presynaptic NMDA receptors and influence synaptic inhibition of Purkinje neurons. J. Neurosci. 2004;24:5659-5669.

    Not in our library10.1523/jneurosci.1338-04.2004

34. 34.

    Ito K, Hicks TP. Effect of the glycine modulatory site of the N-methyl-D- aspartate receptor on synaptic responses in kitten visual cortex. Neurosci. Lett. 2001;303:95-98.

    Not in our library10.1016/s0304-3940(01)01709-8

35. 35.

    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 (DAO) and kynurenine aminotransferase-1 (KAT-1). Brain Res. 2006;1106:205-210.

    Not in our library10.1016/j.brainres.2006.05.082

36. 36.

    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;281:14151-14162.

    Not in our library10.1074/jbc.m512927200

37. 37.

    Katagiri M, Tojo H, Horiike K, Yamano T. Immunochemical relationship of d-amino acid oxidases in various tissues and animals. Comp. Biochem. Physiol. B. 1991;99:345-350.

    Not in our library10.1016/0305-0491(91)90053-g

38. 38.

    Katsetos CD, Hyde TM, Herman M. Neuropathology of the cerebellum in schizophrenia—An update: 1996 and future directions. Biol. Psychiatry. 1997;42:213-224.

    Not in our library10.1016/s0006-3223(96)00313-7

39. 39.

    Kawazoe T, Tsuge H, Imagawa T, Aki K, Kuramitsu S, Fukui K. Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative pathway for dopamine biosynthesis. Biochem. Biophys. Res. Commun. 2007;355:385-391.

    Not in our library10.1016/j.bbrc.2007.01.181

40. 40.

    Konarski JZ, McIntyre RS, Grupp LA, Kennedy SH. Is the cerebellum relevant in the circuitry of neuropsychiatric disorders? J. Psychiatry Neurosci. 2005;30:178-186.

    Not in our library

Cited by papers we hold 1

• Peroxisomes in brain development and function · 2016
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.