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

采用免疫组化方法研究老龄大鼠脑组织中GR的表达。与年轻成年大鼠相比，老龄大鼠的大脑皮层、海马体和杏仁核（与边缘系统密切相关）的gr免疫反应性强度降低，尽管循环皮质类固醇已被表明随着年龄的增长而增加。用高压电镜观察了神经元在衰老过程中的超微结构变化。HVEM可观察到CA1锥体神经元和皮质神经元树突棘数的明显减少，以及这些棘的形态变化。另一方面，我们用免疫组织化学方法研究了几种神经递质相关酶的变化，如ChAT、GAD和TH。在老年大鼠中，与年轻大鼠相比，观察到ChAT的免疫反应性降低，以及GAD。另一方面，老龄大鼠的TH免疫反应强度没有明显变化，但TH免疫反应细胞体和纤维的数量似乎有所减少。此外，我们还研究了不同皮质类固醇条件下垂体前叶卵泡星状细胞中膜联蛋白-1的表达。肾上腺切除术后LC1免疫反应性几乎消失，经皮质酮替代后免疫反应性恢复。GR免疫反应性在FS细胞细胞核中的表达也显示出与皮质类固醇相关的膜联蛋白-1相似的模式，然而S100 （FS细胞的标记物）的免疫反应性在皮质类固醇条件下没有改变。这些结果表明，糖皮质激素调节LC1的表达，促进大鼠垂体前叶FS细胞内膜联蛋白-1从细胞内转运到细胞周围，并作为旁分泌作用与邻近的内分泌细胞相互作用。我们正在研究老龄大鼠膜联蛋白-1表达的变化。少

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