Studies of the brain biochemical analysis and the treatment of schizophrenia

脑生化分析与精神分裂症治疗的研究

基本信息

批准号：
62480243
负责人：
TORU Michio
金额：
$ 4.16万
依托单位：
Tokyo Medical and Dental University (1989)Shinshu University (1987-1988)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

In the analysis of post-mortem brains of 14 chronic schizophrenic patients and 10 controls, we measured the uptake sites of dopamine, benzodiazepine receptors and N-methyl-D-aspartate(NMDA) receptors. Dopamine uptake sites were measured by using ^3-GBR 12935 and a significant increase of specific binding was found in the schizophrenic putamen but not in the caudate. Benzodiazepine receptors, which have never measured in the schizophrenic brain, were analyzed by specific ^3-flunitrazepam binding to 12 brain areas. We found increased specific binding in schizophrenic group to 3 areas of the prefrontal cortex, 2 areas of the temporal cortex and cornu Ammonis. The specific ^3-flunitrazepam binding values positively correlate with GABA contents, the specific ^3-kainate binding values, tyrosine hydroxylase activity, Bmax values of dopamine D2 binding and substance P immunoreactivity while they negatively correlate with glutamic acid contents. ^3-MK801 was used to label the NMDA receptors. Am … More ong 14 brain areas assayed, the specific ^3-MK801 binding was significantly increased in the superior temporal gyrus, the superior parietal cortex and the supra-marginal cortex of schizophrenic patients. The ^3-MK801 binding values positively correlate with ^3-kainate binding values, Bmax values of D2 binding, tyrosine hydroxylase activity, substance P, methionine-enkephalin and CCK-8 immunoreactivity while they negatively correlate with glutamic acid contents.These results suggest that several neuropeptides such as substance P, methionine-enkephalin and CCK-8 function with dopaminergic hyperactivity in the same direction resulting hypofunction of glutamatergic neurons. Subcortical hypoglutamatergic states might induce supersensitivity of glutamate receptors as shown in the increase of ^3-kainate and ^3-MK801 binding. Since these results were obtained from chronic schizophrenic brains, one possibility of developing new drugs to treat chronic states of schizophrenia could be to activate glutamat ergic neurons in the brain. Less

在对 14 名慢性精神分裂症患者和 10 名对照者死后大脑的分析中，我们使用 ^3- 测量了多巴胺、苯二氮卓受体和 N-甲基-D-天冬氨酸 (NMDA) 受体的摄取位点。在精神分裂症壳核中发现 GBR 12935 和特异性结合显着增加，但在尾状核中没有发现。通过与 12 个大脑区域的特异性 ^3-氟硝西泮结合来分析从未在精神分裂症患者大脑中测量过的受体，我们发现精神分裂症患者与前额皮质的 3 个区域、颞叶皮质和阿蒙尼斯角的 2 个区域的特异性结合增加。特异性^3-氟硝西泮结合值与GABA含量、特异性^3-红藻氨酸结合值、酪氨酸羟化酶呈正相关。 ^3-MK801 的活性、多巴胺 D2 结合的 Bmax 值和 P 物质免疫反应性与谷氨酸含量呈负相关，用于标记 NMDA 受体，特别是 ^3-MK801。精神分裂症患者的颞上回、上顶叶皮质和上边缘皮质的结合显着增加。 ^3-MK801结合值与^3-红藻氨酸结合值、D2结合的Bmax值、酪氨酸羟化酶活性、P物质、蛋氨酸脑啡肽和CCK-8免疫反应性呈正相关，而与谷氨酸含量呈负相关。这些结果表明，几种神经肽，如 P 物质、甲硫氨酸脑啡肽和 CCK-8 与多巴胺能亢进作用方向相同，导致多巴胺能功能减退。皮质下谷氨酸能神经元的低谷氨酸能状态可能会引起谷氨酸受体的超敏感性，如 ^3-红藻氨酸和 ^3-MK801 结合的增加所示，因为这些结果是从慢性精神分裂症患者的大脑中获得的，这是开发治疗慢性精神分裂症的新药物的一种可能性。精神分裂症可能会激活大脑中的谷氨酸能神经元。