Clinical and experimental studies on oxidative stress-induced impairment and its treatment in schizophrenia

精神分裂症氧化应激损伤及其治疗的临床与实验研究

基本信息

批准号：
13671007
负责人：
AKIYAMA Kazufumi
金额：
$ 2.56万
依托单位：
Dokkyo University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671007/
关键词：
methamphetamine phencyclidine synaptotagmin Nurr1 neuronal plasticity atypical neuroleptics olanzapine clozapine mRNA behaviural sensitization synaptotagmin SNAP25 synaphin SCH23390 methamphe tamine nitri oxide nNOS MK-80

项目摘要

The effects of acute and chronic administration of methamphetamine (METH) on mRNA levels of synaptotagmin IV (SytIV), synaptic associated protein of 25Kda (SNAP25a) and transcription factor Nurr1 belonging to nuclear receptor superfamily have been investigated in rat brain using in situ hybridization. Pretreatment with SCH23390, but not MK-801, significantly attenuated the acute METH-induced expression levels of SytIV mRNA in the striatum and nucleus accumbens, SNAP 25a mRNA in the striatum and dentate gyros, and Nurr1 mRNA in the in the cerebral cortex, CA1, substantial nigra and ventral segmental area. In the chronic treatment experiment, the SytIV mRNA levels of the group that received chronic treatment with METH followed by a METH challenge were significantly higher in the striatum, nucleus accumbens, somatosensory cortex and dentate gyms than those of the group that received chronic treatment with saline followed by a METH challenge. The SNAP25 a mRNA levels in the striatum and nucleus accumbens, and Nurr1 mRNA levels in the medial frontal cortex, somatosensory cortex and retrosplenial cortex of the group that received chronic treatment with METH followed by a saline challenge were significantly higher than those of the group that received chronic treatment with saline followed by a saline challenge., The effect of pretreatment with a number of neuroleptics on Nurr1 mRNA expression induced by a single administration of phencyclidine, which is an N-methyl-D-aspartate recept or antagonist. Pretreatment with olanzapine and clozapine, but not haloperidol or risperidone, significantly attenuated the increased Nurr1 mRNA levels induced by acute phencyclidine administration in the medial frontal cortex, somatosensory cortex, visual cortex and retrosplenial cortex.

急性和慢性给药甲基苯丙胺（MET）对突触毒素IV（SYTIV）的mRNA水平，25KDA（SNAP25A）的突触相关蛋白和属于核受体超家族核受体超家族的转录因子Nurr1的影响，已在大鼠大脑中使用原位杂交进行了研究。 Pretreatment with SCH23390, but not MK-801, significantly attenuated the acute METH-induced expression levels of SytIV mRNA in the striatum and nucleus accumbens, SNAP 25a mRNA in the striatum and dentate gyros, and Nurr1 mRNA in the in the cerebral cortex, CA1, substantial nigra and ventral segmental area.在慢性治疗实验中，与接受慢性治疗的曲纹，伏隔核，体感皮质和齿状体育体相比，接受甲基苯甲酸甲基的慢性治疗的SYTIV mRNA水平明显高于接受慢性治疗的慢性治疗，然后进行甲酸盐挑战。 SNAP25 A纹状体和副胞核中的SNAP25 mRNA水平，以及该组内部额叶皮层，体感皮质和体感皮质和延性皮质的NURR1 mRNA水平，接受盐水挑战的慢性治疗，随后接受盐水挑战的人的盐分质量高于盐分挑战，该组对盐分的质量进行了高度高于盐水的攻击，该组的盐分均高于盐分。单一给药的苯基二肽诱导的mRNA表达，该苯基酮是N-甲基-D-天冬氨酸或拮抗剂。用奥氮平和氯氮平进行预处理，而不是氟哌啶醇或利培酮，显着减弱了内侧额叶皮质，体感皮质，视觉皮层，视觉皮层和肾后肾上腺皮质的急性苯二酮施用诱导的Nurr1 mRNA水平的升高。