title: Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain.
abstract: D-Amino acid oxidase (DAO) is a peroxisomal flavoenzyme that catalyzes oxidative deamination of a wide range of D-amino acids. Among the possible substrates of DAO in vivo, D-serine is proposed to be a neuromodulator of the N-methyl-D-aspartate (NMDA) type glutamate receptor. The gene for DAO was reported to be associated with schizophrenia. Since DAO is expected to be one of the key enzymes in the regulation of NMDA neurotransmission, the modulation of the enzyme activity is expected to be therapeutical for neuronal disorders. In search of the pathophysiological role of DAO, we analyzed the distribution of DAO mRNA and protein in the rat and human brain. In rat, the distribution of DAO mRNA was newly detected in choroid plexus (CP) epithelial cells in addition to glial cells of pons, medulla oblongata, and especially Bergmann glia of cerebellum. Moreover, to investigate how DAO expression level is altered in schizophrenia, we performed immunohistochemistry in the human brain. In agreement with the results in the rat brain, the immunoreactivity for DAO was detected in glial cells of rhombencephalon and in CP. Furthermore, higher level of DAO expression was observed in schizophrenic CP epithelial cells than that in non-schizophrenic cases. These results suggest that an increase in DAO expression in parts of the brain is involved in aberrant D-amino acid metabolism. In particular, gene expression of DAO in CP suggests that DAO may regulate D-amino acid concentration by modulating the cerebrospinal fluid and may be regarded as a potential therapeutic target for schizophrenia.
authors.affiliation: Division of Enzyme Pathophysiology, The Institute for Enzyme Research, The University of Tokushima, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shishido
authors.forename: Hwan Ki
authors.initials: HK
authors.lastname: Park
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kawazoe
authors.forename: Sanae
authors.initials: S
authors.lastname: Iwana
authors.forename: Seong Pil
authors.initials: SP
authors.lastname: Chung
authors.forename: Rabab M
authors.initials: RM
authors.lastname: Abou El-Magd
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yorita
authors.forename: Mai
authors.initials: M
authors.lastname: Okano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sano
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Arima
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukui
mesh_terms: D000368:Aged; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism*; D002831:Choroid Plexus / Q000201:enzymology / Q000378:metabolism; D003605:D-Amino-Acid Oxidase / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000201:enzymology* / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D012333:RNA, Messenger; D003605:D-Amino-Acid Oxidase
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3089-93
references.pmid: 10716694
references.citation: Schizophr Res. 2008 Apr;101(1-3):76-83
references.pmid: 18378121
references.citation: Biochem Biophys Res Commun. 2007 Apr 6;355(2):385-91
references.pmid: 17303072
references.citation: Gene. 1990 Jun 15;90(2):293-7
references.pmid: 1976103
references.citation: Cell. 1999 Aug 20;98(4):427-36
references.pmid: 10481908
references.citation: Biol Psychiatry. 2005 Mar 15;57(6):577-85
references.pmid: 15780844
references.citation: Eur J Neurosci. 2007 Sep;26(6):1657-69
references.pmid: 17880399
references.citation: Brain Res. 1994 Aug 1;652(2):297-303
references.pmid: 7953743
references.citation: Adv Drug Deliv Rev. 2004 Oct 14;56(12):1695-716
references.pmid: 15381330
references.citation: J Psychopharmacol. 2010 Jul;24(7):1055-67
references.pmid: 19329549
references.citation: FEBS Lett. 1992 Jan 13;296(1):33-6
references.pmid: 1730289
references.citation: Biol Psychiatry. 1998 Dec 1;44(11):1081-9
references.pmid: 9836012
references.citation: Nucleic Acids Res. 1990 Sep 11;18(17):5322
references.pmid: 1698283
references.citation: Arch Gen Psychiatry. 2003 Jun;60(6):572-6
references.pmid: 12796220
references.citation: Proc Natl Acad Sci U S A. 1989 Mar;86(5):1684-8
references.pmid: 2784211
references.citation: Protein Sci. 2006 Dec;15(12):2708-17
references.pmid: 17088322
references.citation: J Neurocytol. 1999 Mar;28(3):169-85
references.pmid: 10617900
references.citation: J Enzyme Inhib Med Chem. 2008 Dec;23(6):901-11
references.pmid: 18615285
references.citation: Biochem J. 1935 Jul;29(7):1620-44
references.pmid: 16745832
references.citation: Biochemistry. 1987 Jun 16;26(12):3612-8
references.pmid: 2888479
references.citation: J Neurochem. 1973 Oct;21(4):1037-9
references.pmid: 4148237
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3948-52
references.pmid: 7732010
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1905-12
references.pmid: 18835577
references.citation: Biochemistry. 1988 Sep 6;27(18):6693-7
references.pmid: 2904274
references.citation: J Biochem. 1990 Sep;108(3):406-13
references.pmid: 1980495
references.citation: Biol Psychiatry. 2005 Jun 15;57(12):1493-503
references.pmid: 15953485
references.citation: J Biol Chem. 1994 Dec 16;269(50):31666-73
references.pmid: 7989339
references.citation: Nucl Med Biol. 2005 Nov;32(8):793-7
references.pmid: 16253803
references.citation: Schizophr Res. 2007 Feb;90(1-3):41-51
references.pmid: 17156977
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4926-31
references.pmid: 10781100
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jun;29(5):767-9
references.pmid: 15939521
references.citation: Chem Rec. 2007;7(5):305-15
references.pmid: 17924443
references.citation: Brain Res Bull. 1987 Nov;19(5):587-96
references.pmid: 2891417
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13675-80
references.pmid: 12364586
references.citation: J Biochem. 2006 Feb;139(2):295-304
references.pmid: 16452318
references.citation: Neurosci Lett. 2002 May 17;324(2):101-4
references.pmid: 11988337
references.citation: J Neurochem. 1997 Sep;69(3):1286-90
references.pmid: 9282954
references.citation: FEBS Lett. 1988 Sep 26;238(1):180-4
references.pmid: 2901986
references.citation: FEBS Lett. 1988 Oct 10;238(2):269-72
references.pmid: 2901989
references.citation: Biol Pharm Bull. 2005 Sep;28(9):1561-5
references.pmid: 16141516
references.citation: Adv Drug Deliv Rev. 2004 Oct 14;56(12):1717-40
references.pmid: 15381331