Effects of MK-801 on the expression of serine racemase and D-amino acid oxidase mRNAs and on the D-serine levels in rat brain
Effects of MK-801 on the expression of serine racemase and D-amino acid oxidase mRNAs and on the D-serine levels in rat brain
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DOI：
10.1016/j.ejphar.2006.09.062
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发表时间：
2007-01-19
影响因子：
5
通讯作者：
Kobayashi, Hiroyuki
中科院分区：
文献类型：
--
作者：
Hashimoto, Atsushi;Yoshikawa, Masanobu;Kobayashi, Hiroyuki
本文研究了非竞争性N-甲基-D-天冬氨酸受体拮抗剂MK-801(0.21.6 mg/kg)剂量增加对大鼠几个脑区丝氨酸外消旋酶和D-氨基酸氧化酶(DAO)mRNAs表达的急性影响。我们还评价了长期给予MK-801(0.4 mg/kg)对丝氨酸消旋酶和DAO基因表达的影响以及对D-丝氨酸浓度的影响。在给药后1h和4h，大部分脑区丝氨酸消旋酶mRNA的表达均呈剂量依赖性增强。MK-801给药后1h，大部分脑区DAO基因表达显著下降，4h后，大部分脑区DAO基因表达呈剂量依赖性升高。慢性给予MK-801后，几乎所有脑区的丝氨酸消旋酶基因表达均显著增加，而大部分脑区DAO基因的表达水平无明显变化。此外，慢性给药引起皮质和纹状体D-丝氨酸浓度轻微但显著升高。这些结果表明，慢性给药后增加丝氨酸消旋酶mRNA和不改变DAO mRNA可能有助于前脑D-丝氨酸水平的升高，丝氨酸消旋酶和DAO可能通过D-丝氨酸代谢在N-甲基-D-天冬氨酸受体的调节中发挥重要作用。(C)2006爱思唯尔B.V.保留所有权利。
We have investigated the acute effects of the increasing doses of non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (0.21.6 mg/kg) on the expression of serine racemase and D-amino acid oxidase (DAO) mRNAs in several brain areas of rats. We have also evaluated the effects of the chronic administration of MK-801 (0.4 mg/kg) on the gene expression of serine racemase and DAO and on the D-serine concentrations. A dose-dependent augmentation of the expression of serine racemase mRNA was seen in most brain areas at both 1 and 4 h after the administration. In contrast, a drastic decline in the expression of DAO mRNA was observed in most brain areas 1 h after the MK-801 administration, whereas a dose-dependent elevation in the expression of DAO mRNA was observed in most brain areas 4 h after the administration. The chronic MK-801 administration produced a significant increase in the expression of serine racemase mRNA in almost all brain areas, whereas no significant changes were found in the level of DAO mRNA in most brain areas. In addition, the chronic administration caused a slight but significant elevation in the concentrations of D-serine in the cortex and striatum. These present findings indicate that increasing the serine racemase mRNA and no changes in the DAO mRNA after the chronic administration could contribute to the elevation of the D-serine level in the forebrain, and that serine racemase and DAO could play an important role in the regulation of N-methyl-D-aspartate receptors via the D-serine metabolism. (c) 2006 Elsevier B.V. All rights reserved.