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，酪氨酸羟化酶阴性和色氨酸羟化酶神经元（D-神经元）在人类的细胞核（ACC）中。 ACC，我们发现球形沉积物（SPDS）在伸缩蛋白的内部和河齿齿状的内部和摩尔层中的大小为3-10μ个体和退化性痴呆症患者。齿状颗粒细胞大约三分之二的树突，而途径贡献了80-85％的突触终端，而该区域与该区域结束相比。隔膜。 /关于海马形成的退化性痴呆症。

项目成果

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 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)

A Nishimura, S Sawada, I Ushiyama, A Tanegashima, T Nakagawa, K Ikemoto, Y Yamamoto, K Satoh, S Rand, B Brinkmann, K Nishi: "Postmortem diagnosis of brain disorders-The histochemical detection of glycoconjugate deposition with lections."Internet Journal o

A Nishimura、S Sawada、I Ushiyama、A Tanegashima、T Nakakawa、K Ikemoto、Y Yamamoto、K Satoh、S Rand、B Brinkmann、K Nishi：“脑部疾病的死后诊断 - 糖复合物沉积的组织化学检测。”

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