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。

基本信息

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

项目摘要

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

我们通过免疫组织化学方法研究了老年大鼠大脑中 GR 的表达，与年轻成年大鼠相比，在与边缘系统密切相关的大脑皮层、海马和杏仁核中观察到 GR 免疫反应强度的降低。在老年大鼠中，虽然循环皮质类固醇已被表明随着衰老而增加。随着衰老，特别是使用高压电子显微镜（HVEM），神经元的超结构变化还观察到HVEM可以揭示CA1锥体神经元和皮质神经元树突中棘的数量显着减少，以及这些棘的形态变化。另一方面，我们通过免疫组织化学研究了几种神经递质相关酶的变化。 ChAT、GAD 和 TH 与年轻大鼠相比，观察到 ChAT 和 GAD 的免疫反应性降低。另一方面，老年大鼠的TH免疫反应性强度没有表现出任何显着变化，尽管TH免疫反应性细胞体和纤维的数量似乎有所减少。此外，我们研究了老年大鼠滤泡星状细胞中annexin-1的表达。垂体前叶在肾上腺切除后，LC1免疫反应性几乎消失，而皮质酮替代后免疫反应性恢复。 FS 细胞的细胞核也显示出与皮质类固醇条件相关的与annexin-1 类似的模式，但是无论皮质类固醇条件如何，S100（FS 细胞的标记物）免疫反应性都没有改变。这些结果表明糖皮质激素调节 LC1 表达并促进易位大鼠垂体前叶 FS 细胞中annexin-1从细胞内到细胞周位点以旁分泌作用与邻近的内分泌细胞相互作用。现将研究老年大鼠annexin-1表达的变化。