title: 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.
authors: Department of Psychiatry, Warneford Hospital, Warneford Lane, University of Oxford, Oxford, UK.
authors: Louise
authors: L
authors: Verrall
authors: Mary
authors: M
authors: Walker
authors: Nancy
authors: N
authors: Rawlings
authors: Isabel
authors: I
authors: Benzel
authors: James N C
authors: JN
authors: Kew
authors: Paul J
authors: PJ
authors: Harrison
authors: Philip W J
authors: PW
authors: Burnet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D003605:D-Amino-Acid Oxidase / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000096:biosynthesis; D019998:Racemases and Epimerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000201:enzymology*; D000099300:Serine Racemase
chemical_list: D014150:Antipsychotic Agents; D003605:D-Amino-Acid Oxidase; D006220:Haloperidol; D012333:RNA, Messenger; D019998:Racemases and Epimerases; D000099300:Serine Racemase