Studies on Brain Actions of the Steroid/Growth Factor System

类固醇/生长因子系统的脑作用研究

• 批准号: 20248030
• 负责人: NISHIHARA Masugi
• 金额: $ 28.79万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20248030/
• 关键词: 脳・神経; ステロイドホルモン; 成長因子; プログラニュリン; 神経新生; 神経変性; 性分化; 組織幹細胞

This study was conducted to elucidate the role of sex steroid/growth factor systems in sexual differentiation of the brain during perinatal period and neuroprotection as well as neurogenesis after maturation. By the studies using progranulin(PGRN)-deficient mice we have generated, we found that PGRN mediates the brain actions of estrogens and modulates brain sexual differentiation, neurogenesis in the dentate gyrus of the hippocampus and neurodegeneration. It is also demonstrated that PGRN plays a role in regulating the activation of microglia after traumatic brain injury. In addition, it is suggested that the actions of PGRN in the brain is transduced through glycogen synthase kinase 3βphosphorylation, and mediated by genes/proteins containing LIM domain.

本研究旨在阐明性类固醇/生长因子系统在围产期脑性别分化和成熟后的神经保护和神经发生中的作用。通过对PGRN缺陷小鼠的研究，我们发现PGRN介导雌激素的脑活动，调节脑性别分化、海马齿状回神经发生和神经退行性变。PGRN还参与了脑外伤后小胶质细胞的激活调控。此外，我们认为PGRN在脑中的作用是通过糖原合成酶激酶3β磷酸化转导的，并由含有LIM结构域的基因/蛋白介导。

项目成果

Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggests a role for progranulin in successful aging.

颗粒体蛋白敲除小鼠中加速的脂褐质沉着和泛素化表明颗粒体蛋白前体在成功衰老中的作用。

• 发表时间: 2010
• 期刊: Am J Pathol 177
• 作者: Ahmed Z;Sheng H;Xu YF;Lin WL;Innes A;Yu X;Hou H;Chiba S;Yamanouchi K;Petrucelli L;Nishihara M;Hutton ML;McGowan E;Dickson D;Lewis J
• 通讯作者: Lewis J

Progranulin suppresses excessive activation of CD68-positive microglia following traumatic brain injury in mice

颗粒体蛋白前体抑制小鼠脑外伤后 CD68 阳性小胶质细胞的过度激活

• 发表时间: 2011
• 作者: Tanaka Y;Matsuwaki T;Yamanouchi K;Nishihara M
• 通讯作者: Nishihara M

グラニュリンノックアウトマウス視床下部における遺伝子およびタンパク質の網羅的発現解

颗粒蛋白敲除小鼠下丘脑基因和蛋白的综合表达分析

• 发表时间: 2008
• 作者: 板村理央;他
• 通讯作者: 他

Alteration in Anxiety with Relation to the Volume of the Locus Ceruleus in Progranulin-Deficient Mice

• DOI: 10.1262/jrd.20239
• 发表时间: 2009-10-01
• 期刊: JOURNAL OF REPRODUCTION AND DEVELOPMENT
• 影响因子: 1.8
• 作者: Chiba, Shuichi;Matsuwaki, Takashi;Nishihara, Masugi
• 通讯作者: Nishihara, Masugi

Age-dependent changes in progranulin expression in mouse brain.

小鼠大脑中颗粒体蛋白前体表达的年龄依赖性变化。

• 发表时间: 2011
• 期刊: J Reprod Dev 57
• 作者: Matsuwaki T;Asakura R;Suzuki M;Yamanouchi K;Nishihara M
• 通讯作者: Nishihara M