A research for molecular level characteristics of monoaminergic neurons in schizophrenia by means of histochemical approach on autopsied human brains

利用尸检人脑的组织化学方法研究精神分裂症单胺能神经元的分子水平特征

• 批准号: 12680740
• 负责人: NISHIMURA Akiyoshi
• 金额: $ 2.18万
• 依托单位: Yokohama City University School of Medicine (2002)Shiga University of Medical Science (2000-2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680740/
• 关键词: sepiapterin reductase; immunohistochemistry; tyrosine hydroxylase; tetrahydrobiopterin; monoamine; nucleus accumbency; aromatic L-amino acid decarboxylase; schizophrenia; immunohistochemistry; モノアミン; 精神分裂病; セロトニン2Aレセプター; チロシン水酸化酵素; 芳香族アミノ酸脱炭酸

In this study, we found many Aromatic L-amino acid decarboxylase positive, tyrosine hydroxylase negative and tryptophan hydroxylase negative neurons (D-neurons) in the nucleus (Acc) of human. The number of D-neurons in schizophrenic patients was significantly lower than in controls (p<0.05, t-test) in the Acc. And, we found the spherical deposits (SPDs) with a size of 3-10μ in diameter mainly within the inner and middle molecular layer of the dentate gyrus of hippocampal formation by lectin staining. The number of the SPDs in schizophrenic patients was higher than in aged individuals and degenerative dementia patients. The Acc receives fiber projections of excitatory amino acid from the hippocampus, anterior cingulate cortex, amygdala and thalamus, and the nucleus projects to ventral palladium and midbrain. The Acc is thought to be an interface that converts emotion to action and to relate to the etiology of schizophrenia. The perforate pathway synapses on the outer portion of the dentate that arises from the dentate gyrus granule cells. This subtends approximately two-thirds of the granule cell dendrites and the perforate pathway contributes 80-85% of the synaptic terminals that end in this zone. By contrast, the inner one-third portion of the molecular layer receives afferents from the CA4 zone and from the septum. The presence of many SPDs in the molecular layer of the dentate gyrus suggests that there may exist a disadvantageous interaction between these deposits and dendrites of neurons of the CA4 zone of the hippocampus and may play a key part in the perturbation of the memory of patients with schizophrenia and/or degenerative dementias. Concerning the hippocampal formation, hypotheses of a possible hippocampal etiology of schizophrenia have been formulated. This study suggests that D-neurons in the Acc and SPDs in the dentate gyrus of hippocampal formation may relate to the pathology of schizophrenia.

在这项研究中，我们在人类的核（ACC）中发现了许多芳香族L-氨基酸脱羧酶阳性，酪氨酸羟化酶阴性和色氨酸羟化酶阴性神经元（D-神经元）。精神分裂症患者的D-神经元数量明显低于ACC中对照组（p <0.05，t检验）。而且，我们发现直径为3-10μ的球形沉积物（SPD）主要在海马形成的齿状回的内部和中部分子层内，通过secretin染色。精神分裂症患者中的SPD数量高于年龄个体和退化性痴呆症患者的数量。 ACC从海马，前扣带回皮质，杏仁核和丘脑的兴奋性氨基酸接收纤维项目，核将其投射到腹钯和中脑。 ACC被认为是将情绪转化为动作并与精神分裂症病因相关的界面。齿状回颗粒细胞产生的齿状齿外部的穿孔途径突触。这将大约三分之二的颗粒细胞树突介绍，并且穿孔途径占该区域结束的突触终端的80-85％。相比之下，分子层的内部三分之一部分从CA4区和隔膜接收传入。齿状回的分子层中许多SPD的存在表明，这些沉积物与海马CA4区域的神经元之间可能存在不良相互作用，并且可能在患者与精神分裂症和/或退化性痴呆症患者的记忆中起关键作用。关于海马形成，已经提出了精神分裂症海马病因的假设。这项研究表明，海马形成齿状回的ACC和SPD中的D-神经元可能与精神分裂症的病理有关。

项目成果

A Nishimura, S Sawada, I Ushiyama, A Tanegashima, Y Yamamoto, K Ikemoto, K Satoh, K Nishi: "The aberrant glycogenesis in the fippocampus of schizophrenia"Acta Crininologiae et Medicine Legalis Japonica. 67巻2号. 49-55 (2001)

A Nishimura、S Sawada、I Ushiyama、A Tanegashima、Y Yamamoto、K Ikemoto、K Satoh、K Nishi：“精神分裂症海波回的异常糖生成”Acta Crininologiae et Medicine Legalis Japonica，第 67 卷，第 49 卷。 -55 (2001)

池本桂子: "ヒト線条体D-ニューロンとその意義"日本神経精神薬理学雑誌. 22. 131-135 (2001)

Keiko Ikemoto：“人类纹状体 D 神经元及其意义”，《日本神经精神药理学杂志》22. 131-135 (2001)。

K Ikemoto, A Nishimura, N Okado, M Mikuni, K Nishi, I Nagatsu: "Human midbrain dopamine neurons express serotonin 2A receptor : a immunohistochemical demonstration"Brain Research. 853. 377-380 (2000)

K Ikemoto、A Nishimura、N Okado、M Mikuni、K Nishi、I Nagatsu：“人类中脑多巴胺神经元表达血清素 2A 受体：免疫组织化学演示”大脑研究。

A Nishimura, S Sawada, I Ushiyama, A Tanegashima, Y Yamamoto, K Ikemoto, K Satoh, K Nishi: "The aberrant glycogenesis in the hippocampus of schizophrenia."Acta Criminological et Medicine Legalist Japonica. 67(2). 49-55 (2001)

A Nishimura、S Sawada、I Ushiyama、A Tanegashima、Y Yamamoto、K Ikemoto、K Satoh、K Nishi：“精神分裂症海马体糖生成异常。”Acta Criminological et Medicine Legalist Japonica。

M Ota, A Nakashima ,K Ikemoto, S Nojima, M Tanaka, M Okuda, Hkoga, K Mori, YS Kaneko, K Fujiwara, H Yamamoto, T Nagatsu, A Ota: "Exon 3 of tyrosine hydroxylase gene: lack of association with Japanese schizophrenic patients."Molecular Psychiatry. 6. 315-31

M Ota、A Nakashima、K Ikemoto、S Nojima、M Tanaka、M Okuda、Hkoga、K Mori、YS Kaneko、K Fujiwara、H Yamamoto、T Nagatsu、A Ota：“酪氨酸羟化酶基因的外显子 3：缺乏与