Pathological elucidation of autism by using morphological multi-parameter analysis in neuron and microglia co-culture system

利用神经元和小胶质细胞共培养系统的形态学多参数分析对自闭症进行病理学阐明

• 批准号: 20H03597
• 负责人: 染矢 俊幸
• 金额: $ 11.07万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20H03597/
• 关键词: 自閉スペクトラム症; 培養神経細胞; ハイコンテントスクリーニング; High Content Screening; Kinase inhibitor; 自閉症; 拝コンテントスクリーニング; シナプス; ミクログリア

自閉スペクトラム症（Autism Spectrum Disorder; ASD）のリスク遺伝子の変異を加えた培養神経細胞の変化を指標としてHigh Content Screeningの技術を用いて形態的マルチパラメータ（神経細胞数、神経突起長、シナプス数）を用いることとした。しかしこれまでにHCSによるシナプス数カウントの実験系が確立していないため、その実験系の確立を行った。シナプス発達および精神神経疾患に関連が報告されているKinase (AKT, TNIK, DYRK1A, TAOK2, GAK)に注目し(Crino, 2015; Duchon and Herault, 2016; Baltussen et al., 2018)、計5種類のKinase inhibitor（CP43, AKTi-1/2, Harmine, PF0626033, LRRK2IN-1, JH-II-127, MLi-2, GSK2578215A, SGC-GAK-1）をそれぞれ添加した。結果全てのKinase inhibitorにおいて（それぞれn=6）DMSOのみ添加のコントロール(n=6)に比して神経突起長、シナプス数が有意に減少していることを確認した。そのうちSGC-GAK-1は近年確立された非常に選択性の高い阻害剤であり(Asquith et al., 2019)、そのリン酸化阻害作用が神経発達に負の影響（神経突起長およびシナプス数の減少）を与えるという研究結果が結果がMol brain誌に採択された (Egawa et al., 2022)。またASDの有力なリスク遺伝子であり、特に聴覚過敏に関連するCNTN5のエクソンシークエンスをASD患者のDNAサンプルにて行い、in silico解析により有害と判定された4つの変異を同定した。

Self-inflicted typhoid disease (Autism Spectrum Disorder; ASD). The number of cells (number of cells, the length of protuberances, and the number of trunks) is used in the technology of self-inflicted disease (Autism Spectrum Disorder; ASD). It refers to the number of cells (the number of cells, the length of protuberances, the number of cells) that are used in the technology of self-inflicted virus. Please tell me that you need to make sure that you have made a reservation. The report on mental disorders (AKT, TNIK, DYRK1A, TAOK2, GAK) paid close attention to Crino (Crino, 2015; Duchon and Herault, 2016; Baltussen et al., 2018) and added five categories of Kinase inhibitor (CP43, AKTi-1/2, Harmine, PF0626033, LRRK2IN-1, JH-II-127, MLi-2, GSK2578215A, SGC-GAK-1). Results the results showed that the protuberance of the whole Kinase inhibitor was longer than that of the control, and the number of samples was significantly lower than that of the total number of patients. The results showed that the total number of Kinase inhibitor signals was longer than that of the patients, and the number of patients was significantly higher than that of the controls. In recent years, we have established that there is a very high level of selective blocking effect (Asquith et al., 2019), that the effect of acidification is very high (Asquith et al., 2019), that the protective effect of acidification is very high, and that the effect of acidification is very effective. The results of the study showed that the effects of acidification and acidification were very effective. The results of the study showed that the effects of acidification and acidification were very effective (Egawa et al., 2022). The results showed that the patients with ASD suffered from ASD, the patients with ASD suffered from DNA, the patients with ASD, and the patients with ASD.

项目成果

ついに完成! 統合失調症薬物治療ガイドライン改訂版2022

精神分裂症药物治疗指南2022年修订版终于完成！

• 发表时间: 2022
• 作者: Ezura M;Kikuchi A;Okamura N;Ishiki A;Hasegawa T;Harada R;Watanuki S;Funaki Y;Hiraoka K;Baba T;Sugeno N;Yoshida S;Kobayashi J;Kobayashi M;Tano O;Ishiyama S;Nakamura T;Nakashima I;Mugikura S;Iwata R;Taki Y;Furukawa K;Arai H;Furumoto S;染矢俊幸
• 通讯作者: 染矢俊幸

Withdrawal from long‐term use of caffeinated drinks can cause schizophrenia‐like symptoms: A case report

戒断长期饮用含咖啡因饮料可能导致精神分裂症样症状：病例报告

• DOI: 10.1111/pcn.13199
• 发表时间: 2021
• 期刊: Psychiatry and Clinical Neurosciences
• 影响因子: 11.9
• 作者: Onda Keigo;Yukawa Takayuki;Sakaue Masashi;Tsuboya Ryusuke;Inoue Emiko;Someya Toshiyuki
• 通讯作者: Someya Toshiyuki

Elevation of EGR1/zif268 in the auditory cortex of patients with schizophrenia and its animal model.

精神分裂症患者及其动物模型听觉皮层EGR1/zif268的升高

• 发表时间: 2022
• 作者: Iwakaura Y;Kawahara-Miki R;Kida S;Sotoyama H;Gabdulkhaev R;Takahashi H;Kunii Y;Hino M;Nagaoka A;Izumi R;Shishido R;Someya T;Yabe H;Kakita A;Nawa H
• 通讯作者: Nawa H

前頭側頭型認知症に類似したCushing病によるパーソナリティ変化の1例.

与额颞叶痴呆类似的库欣病引起的人格改变病例。

• 发表时间: 2021
• 作者: 熊谷航一郎;横山裕一;大竹雅也;渡部雄一郎;染矢俊幸
• 通讯作者: 染矢俊幸

Effects of GAK inhibition on Neurite Outgrowth and Synapse Formation

GAK 抑制对神经突生长和突触形成的影响

• 发表时间: 2022
• 作者: Kubo Hiroaki;Urata Hiromi;Katsuki Ryoko;Hirashima Miyako;Ueno Shion;Suzuki Yuriko;Fujisawa Daisuke;Hashimoto Naoki;Kobara Keiji;Cho Tetsuji;Mitsui Toshiko;Kanba Shigenobu;Otsuka Kotaro;Kato Takahiro A.;布村明彦;Jun Egawa
• 通讯作者: Jun Egawa