Brain Expression of Neurotrophins and Its Relation to Schizophrenia

神经营养素的脑表达及其与精神分裂症的关系

• 批准号: 10670133
• 负责人: NAWA Hiroyuki
• 金额: $ 1.6万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670133/
• 关键词: schizophrenia; neurotrophin; phencyclidine; BDNF; sytokine; postmortem brain; neurotrophic

In schizophrenic patients, pathological abnormality has been often found in the corticolimbic regions including prefrontalcortex and cingulate cortex.. Based on the hypothesis that developmental impairments in the brain involves schizophreniaetiology, we have investigated contribution of neuronal differentiation factors, neurotrophins, to this disease, which playcrucial roles in brain development. We measured levels of the three neurotrophins, NGF, BDNF and NT-3 in the postmortem brains by using a sandwich immunoassay. BDNF levels were increased in the hippocampus and cingulate cortex, but not in the other areas nor NT-3 levels in all the regions. These changes in BDNF levels were seen in the off-drug patients, excluding influences of neuroleptic treatments on BDNF. In addition, we also examined the expression of neurotrophins in the mode lanimals for schizophrenia, to which phencyclidine (PCP) had been administered chronically. In agreement, BDNF levels were elevated in the cingulate cortex and entorhinal cortex but NT-3 levels were not altered. These results suggest that abnormal expression of BDNF in the corticolimbic system contributes to the etiology or pathology of this disease.

在精神分裂症患者中，病理性异常常出现在皮质边缘区，包括前额叶皮层和扣带皮层。基于大脑发育障碍与精神分裂症病因学有关的假设，我们研究了神经元分化因子，即神经营养因子，在大脑发育中起着至关重要的作用。我们使用三明治免疫分析法测量了死后大脑中三种神经营养因子，NGF， BDNF和NT-3的水平。海马和扣带皮层的BDNF水平升高，但其他区域没有升高，所有区域的NT-3水平也没有升高。这些BDNF水平的变化在停药患者中可见，不包括抗精神病药物治疗对BDNF的影响。此外，我们还检测了长期服用苯环利定（PCP）的精神分裂症模型动物中神经营养因子的表达。与此一致的是，扣带皮层和内嗅皮层的BDNF水平升高，但NT-3水平没有改变。这些结果提示，BDNF在皮质边缘系统中的异常表达有助于本病的病因或病理。

项目成果

H. Nawa 他2名: "Cytokine and Growth Factor Involvement in Schizophenia"Molecular Psychiatry. (印刷中). (2000)

H. Nawa 和其他 2 人：“细胞因子和生长因子参与精神分裂症”分子精神病学（2000 年出版）。