A CSF and postmortem brain study of D-serine metabolic parameters in schizophrenia

被引:271
作者
Bendikov, Inna
Nadri, Carmit
Amar, Shirly
Panizzutti, Rogerio
De Miranda, Joari
Wolosker, Herman [1 ]
Agam, Galila
机构
[1] Technion Israel Inst Technol, B Rappaport Fac Med, Dept Biochem, IL-31096 Haifa, Israel
[2] Ben Gurion Univ Negev, Fac Hlth Sci, Stanley Res Ctr, IL-84105 Beer Sheva, Israel
[3] Univ Fed Rio de Janeiro, Dept Anat, BR-21941 Rio De Janeiro, Brazil
[4] Univ Fed Rio de Janeiro, Dept Biochem, BR-21941 Rio De Janeiro, Brazil
关键词
serine racemase; D-amino acid oxidase; schizophrenia; postmortem brain; CSF; D-serine; AMINO-ACID OXIDASE; RAT-BRAIN; CEREBROSPINAL-FLUID; RACEMASE; GLUTAMATE; LOCALIZATION; HIPPOCAMPUS; EXPRESSION; COAGONIST; DIAGNOSIS;
D O I
10.1016/j.schres.2006.10.010
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Clinical trials demonstrated that D-serine administration improves schizophrenia symptoms, raising the possibility that altered levels of endogenous D-serine may contribute to the N-methyl D-aspartate receptor hypofunction thought to play a role in the disease. We hypothesized that cerebro-spinal fluid (CSF) D-serine levels are decreased in the patients due to reduced synthesis and/or increased degradation in brain. We now monitored amino acid levels in CSF from 12 schizophrenia patients vs. 12 controls and in postmortem parietal-cortex from 15 control subjects and 15 each of schizophrenia, major-depression and bipolar patients. In addition, we monitored postmortem brain serine racemase and D-amino acid oxidase protein levels by Westem-blot analysis. We found a 25% decrease in D-serine levels and D/L-serine ratio in CSF of schizophrenia patients, while parietal-cortex D-serine was unaltered. Levels Of L-serine, L-glutamine and L-glutamate were unaffected. Frontal-cortex (39%) and hippocampal (21%) serine racemase protein levels and bippocampal serine racemase/D-amino acid oxidase ratio (34%) were reduced. Hippocampal D-ammokid-oxidase piotein levels significantly correlated with duration of illness (r = 0.6, p = 0.0 19) but not age. D-amino acid oxidase levels in patients with DOI > 20 years were 77% significantly higher than in the other patients and controls. Our results suggest that reduced brain serine racemase and elevated D-amino acid oxidase protein levels may contribute to the lower CSF D-serine levels in schizophrenia. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:41 / 51
页数:11
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