Molecular and cellular analysis of the changes of the expression of steroid hormone receptors and the neuronal function associated with aging.

类固醇激素受体表达变化及与衰老相关的神经元功能的分子和细胞分析。

• 批准号: 11680791
• 负责人: OZAWA Hitoshi
• 金额: $ 2.37万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680791/
• 关键词: Aging; Glucocorticoid receptor; Steroid hormone; Immunohistochemistry; Ultra structure; High voltage electron microscopy; Neuroendocrine; Neurotransmitter; ステロイドホルモン受容体; ラット; グルココルチコイド; アネキシン1; 転写調節; 共役転写因子; 免疫電子顕微鏡

We immunohistochemically investigated the GR expression in the brain of aged-rats by means of. In comparison with young adult rats, the reduction of intensity for GR-immunoreactivity was observed in the cerebral cortex, hippocampus and amygdala, which were well associated to the limbic system, in the aged-rats, although the circulating cortiosteroids have been indicated to show an increase with aging.The ultra structural changes on the neurons with aging, especially using a high voltage electron microscopy (HVEM) was also observed. HVEM could reveal the significant reduction of the number of spines in dendrites of CA1 pyramidal neurons and cortical neurons, and the morphological changes of these spines. On the other hand, we immunohistochemically investigated the change of several neurotransmitter relevant enzymes, such as ChAT, GAD, and TH. In the aged rats, the reduction of immunoreactivity for ChAT, as well as GAD were observed in comparison with those in the young rats. On the othe … More r hand, the intensity of TH immunoreactivity did not show any significant changes in aged rats, although the number of TH-immunoreactive cell bodies and fibers seemed to reduce.Moreover, we studied about the expression of annexin-1 in the folliculo-stellate cells in the anterior pituitary under different corticosteroid conditions. After adrenalectomy, LC1 immunoreactivity was almost disappeared, while the immunoreactivity was recovered by corticosterone replacement. The expression of GR immunoreactivity in the nucleus of FS cells also showed a similar pattern to annexin-1 associated with the corticosteroids conditions, however S100 (a marker for FS cells) immunoreactivity was not changed whatever corticosteroids conditions.These results suggest that glucocorticoids regulate the LC1 expression and promote the translocation of annexin-1 from intracellular to pericellular sites in the FS cells of rat anterior pituitary gland to interact with neighboring endocrine cells as a paracrine action. The change of annexin-1 expression in the aged rat is now going to investigate. Less

我们用免疫组织化学方法研究了老年大鼠脑内GR的表达。与青年大鼠相比，老年大鼠大脑皮质、海马体和杏仁核中与边缘系统密切相关的GR免疫反应强度降低，尽管循环中的皮质类固醇激素随着年龄的增长而增加。HVEM可显示CA1区锥体神经元和皮质神经元树突内的棘细胞数量明显减少，并可显示这些棘细胞的形态变化。另一方面，我们用免疫组织化学方法检测了几种神经递质相关酶如ChAT、GAD和TH的变化。老年大鼠与青年大鼠比较，ChAT、GAD免疫反应减弱。在Othe…上此外，尽管TH免疫反应胞体和纤维数量减少，但老年大鼠的TH免疫反应强度没有明显变化。此外，我们还研究了不同糖皮质激素条件下，Annexin-1在垂体前叶滤泡星状细胞中的表达。肾上腺切除后，Lc1免疫反应基本消失，皮质酮替代治疗可恢复其免疫反应。在激素作用下，FS细胞胞核的GR免疫反应性表达与Annexin-1相似，而作为FS细胞标志物的S100在激素条件下不发生变化。这些结果提示，糖皮质激素可以调节脑脊液细胞Lc1的表达，促进Annexin-1从细胞内移位到细胞外，与邻近的内分泌细胞相互作用，起旁分泌作用。现对老年大鼠脑内膜联蛋白-1的表达变化进行研究。较少

项目成果

Ozawa H,Ito T,Ochiai I,Kawata M.: "Cellular localization and distribution of glucocorticoid receptor immunoreactivity and the expression of glucocorticoid receptor messenger RNA in rat pituitary gland.A combined double immunohistochemistry and in situ hyb

Ozawa H，Ito T，Ochiai I，Kawata M.：“大鼠垂体中糖皮质激素受体免疫反应性的细胞定位和分布以及糖皮质激素受体信使 RNA 的表达。联合双重免疫组织化学和原位杂交

Nishi M., Takenaka N., Morita N., Ito T., Ozawa H., Kawata M.: "Real-time imaging of glucocorticoid receptor dynamics in living neurons and glial cells in comparison with non-neural cells"Eur J Neurosci. 11. 1927-1936 (1999)

Nishi M.、Takenaka N.、Morita N.、Ito T.、Ozawa H.、Kawata M.：“与非神经细胞相比，活体神经元和神经胶质细胞中糖皮质激素受体动态的实时成像”Eur J Neurosci

小澤一史, 謝 蔵霞, 落合育雄, 河田光博: "視床下部領域おけるグルココルチコイド受容体の発現とその意義"電子顕微鏡. 36. 45-47 (2001)

Kazushi Ozawa、Zangxia Xie、Ikuo Ochiai、Mitsuhiro Kawata：“下丘脑区域糖皮质激素受体的表达及其意义”电子显微镜学36. 45-47 (2001)。

Xie C-X., Ozawa H., Yang Y., Kawata M.: "Immunohistochemical study of nucleoporin p62 in the hippocampus and hypothalamus"NeuroReport. 11. 2965-2967 (2000)

Xie C-X.，Ozawa H.，Yang Y.，Kawata M.：“海马和下丘脑核孔蛋白 p62 的免疫组织化学研究”NeuroReport。

Ozawa H, Lion J, Xie CX, Nishi M, Steinbusch H, Kawata M: "Down-regulation of ACTH and glucocorticoid receptor immunoreactivity in hvnothalamic arcuate neurons after adrenalectomy in the rat"NeuroReport. 10. 1571-1575 (1999)

Ozawa H、Lion J、Xie CX、Nishi M、Steinbusch H、Kawata M：“大鼠肾上腺切除术后下丘脑弓状神经元中 ACTH 和糖皮质激素受体免疫反应性的下调”NeuroReport。