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.

在本研究中，我们在人的大脑皮质内发现了大量的芳香族L氨基酸脱羧酶阳性神经元(D神经元)，酪氨酸羟基酶阴性神经元和色氨酸羟基酶阴性神经元(D神经元)。在ACC中，精神分裂症患者的D神经元数量显著低于对照组(P&lt；0.05，t检验)。凝集素染色发现直径为3~10μ的球形沉积物主要分布在海马齿状回的内层和中分子层。精神分裂症患者的SPD数量高于老年组和退行性痴呆患者。ACC接受来自海马体、前扣带回皮质、杏仁核和丘脑的兴奋性氨基酸纤维投射，核团投射到腹侧钯和中脑。ACC被认为是一个将情绪转化为行动的界面，与精神分裂症的病因有关。穿孔通路与齿状回颗粒细胞形成的齿状回外侧突触。它覆盖了大约三分之二的颗粒细胞树突，穿孔通路贡献了终止于该区域的突触终末的80%-85%。相反，分子层内三分之一的部分接受来自CA4区和隔区的传入神经。齿状回分子层中大量SPD的存在，提示这些沉积可能与海马区CA4区神经元树突之间存在着不利的相互作用，可能在精神分裂症和/或退行性痴呆患者记忆障碍中起关键作用。关于海马区结构，关于精神分裂症可能的海马区病因学的假说已经被提出。本研究提示，海马齿状回ACC和SPD中的D神经元可能与精神分裂症的病理机制有关。

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