Clarification on the role of semaphorin signal transduction mechanism regulating microglial function in brain homeostasis

阐明信号蛋白信号转导机制调节小胶质细胞功能在脑稳态中的作用

• 批准号: 22590195
• 负责人: YUKAWA Kazunori
• 金额: $ 3万
• 依托单位: Meijo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590195/
• 关键词: 発生学; 形態形成学; セマフォリン; ミクログリア; 脳内ホメオスターシス; プレキシン; 脳内炎症; 精神疾患; 細胞分化・組織形成; 那須-ハコラ病

Plexin-A1 is a receptor of semaphorins originally found as repulsive axon guidance molecules. Plexin-A1 deficient mice over 14-week-old were revealed to have significant deficits in prepulse inhibition of auditory startle reflex which can be also observed in psychiatric disease such as schizophrenia. Plexin-A1 deficient mice also displayed significant increase in locomotion activity and grooming behavior and age-dependent microglial overactivation and demyelination. Thus, plexin-A1 deficient mice is an animal model useful to obtain a novel finding which helps us clarify the pathogenic mechanism of psychiatric diseases recently suggested to be related to abnormal microglia, but still concealing essentially unknown factors.

Plexin-A1 是信号蛋白的受体，最初被发现是作为排斥性轴突引导分子。研究发现，14 周以上的 Plexin-A1 缺陷小鼠在听觉惊吓反射的前脉冲抑制方面存在显着缺陷，这在精神分裂症等精神疾病中也可以观察到。 Plexin-A1 缺陷小鼠的运动活动和梳理行为以及年龄依赖性小胶质细胞过度激活和脱髓鞘也表现出显着增加。因此，plexin-A1缺陷小鼠是一种有助于获得新发现的动物模型，该发现有助于我们阐明最近被认为与异常小胶质细胞有关的精神疾病的致病机制，但仍然掩盖了本质上未知的因素。

项目成果

Selective toxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells is potentially attributed to downregulation of glutathione.

• DOI: 10.1016/j.biochi.2011.04.011
• 发表时间: 2011-07
• 期刊: Biochimie
• 影响因子: 3.9
• 作者: H. Yamaguchi;T. Yu;Y. Kidachi;T. Akitaya;K. Yoshida;K. Kamiie;T. Noshita;H. Umetsu;K. Ryoyama

Mechanism of postnatal tissue remodeling induced by Sema4D/CD100 in mice.

Sema4D/CD100诱导小鼠产后组织重塑的机制。

• 发表时间: 2010
• 作者: Takuji Ito;Tao Bai;Tetsuji Tanaka;Takashi Ueyama;Kenji Yoshida;Noriko Takeuchi;Hyota Takamatsu;Hitoshi Kikutani;Atsushi Kumanogoh;and Kazunori Yukawa
• 通讯作者: and Kazunori Yukawa

Specific downregulation of death-associated protein kinase enhances Fas-mediated apoptosis in the human differentiated endometrial

死亡相关蛋白激酶的特异性下调增强了人分化子宫内膜中 Fas 介导的细胞凋亡

• 发表时间: 2011
• 期刊: Eur J Gynaecol Oncol
• 影响因子: 0.4
• 作者: Tanaka T;Bai T;Yukawa K
• 通讯作者: Yukawa K

Targeted knockdown of death-associated protein kinase expression induces TRAIL-mediated apoptosis in human endometrial adenocarcinoma cells. Int.

死亡相关蛋白激酶表达的靶向敲低可诱导人子宫内膜腺癌细胞中 TRAIL 介导的细胞凋亡。

• 发表时间: 2010
• 期刊: J. Oncol.
• 作者: Tao Bai;Tetsuji Tanaka and Kazunori Yukawa
• 通讯作者: Tetsuji Tanaka and Kazunori Yukawa

進行期婦人科悪性腫瘍にともなう尿管閉塞性水腎症の分子機構解析.

晚期妇科恶性肿瘤相关输尿管梗阻性肾积水的分子机制分析

• 发表时间: 2010
• 作者: 田中哲二;湯川和典
• 通讯作者: 湯川和典