ESTROGEN REGULATES CYTOKINE EXPRESSION IN THE CEREBELLUM

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们建议调查雌激素与脑巨噬细胞（小胶质细胞）在老龄雌性大鼠小脑。运动能力随着年龄的增长而下降，这表明小脑细胞的早熟变性对运动结构有长期影响。小胶质细胞是炎性细胞因子的丰富来源，并且当被激活时，已经在病理条件下被记录。然而，雌激素以及一些细胞因子，例如，IL-6，对脑内突触可塑性有增强作用，对记忆有巩固作用。虽然小脑传统上不被认为是雌激素反应区域，但最近的研究揭示了雌激素受体的存在。在这项研究中，我们的目标是阐明与年龄相关的雌激素损失，细胞因子的产生，以及它们对阳性细胞密度和分布的综合影响之间的关系。使用单/双标记免疫细胞化学和光学显微镜，我们将确定，使用小胶质细胞标志物OX-42和IL-α，β，IL-6和TNF α的细胞因子标志物，免疫阳性细胞的密度和分布。已知这些特定的细胞因子与衰老相关。我们将确定是否年龄相关的雌激素损失导致小脑小胶质细胞的迁移和/或增殖潜力降低，以及是否调节在老年大鼠小胶质细胞中鉴定出的精氨酸阳性细胞的表达。基本原理是因为我们知道雌激素可以作为一种免疫保护剂，年龄相关的雌激素丢失可能导致小脑小胶质细胞中细胞因子受体的上调，从而启动可能影响小脑功能的反应。 更重要的是，这是我们的目标，以获得有效的，精确的，公正的，可靠的估计标记的小胶质细胞的数量和形态学特性，以及那些可能表达细胞因子。神经生物学和计算机的整合将使我们能够将收集到的有关小脑老化的信息存储到共享数据库中，这对计算神经科学领域非常有用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to investigate estrogens association with brain macrophages (microglial cells) in the cerebellum of aging female rats. Motor abilities decrease with age, suggesting that precocious degeneration of cerebellar cells have long-term effects on motor structures. Microglia are rich sources for inflammatory cytokines, and when activated, have been documented in pathological conditions. However, the actions of estrogens, as well as some cytokines, e.g., IL-6, on the brain have been their enhancement of synaptic plasticity and memory consolidation. Although the cerebellum has not traditionally been considered an estrogen responsive region, recent studies reveal the presence of estrogen receptors. In this study, our goal is to elucidate the relationship between age-related loss of estrogen, the production of cytokines, and their integrative affects on positive cell density and distribution. Using single-/double-labeling immunocytochemistry and light microscopy, we will identify, using the microglial marker OX-42 and the cytokine markers for IL-alpha, -beta, IL-6, and TNF alpha, the density and distribution of immunopositive cells. These specific cytokines are known to be associated with aging. We will determine if age-related loss in estrogen causes a decrease in the migratory and/or proliferative potential of microglia in the cerebellum, and if it regulates the expression of cytokine-positive cells that are identified in microglia of aged rats. The rationale is since we know that estrogen may serve as an immunoprotective agent, age-related loss of estrogen may result in up-regulation of cytokine receptors in cerebellar microglia, thus initiating a response that may affect cerebellar function. More importantly, it is our goal to obtain efficient, precise, unbiased, and reliable estimates of the number and morphometric properties of labeled microglial cells, and those that may express cytokines. Integration of neurobiology and computers will enable us to store information gathered about aging cerebella into shared databases proving useful to the field of computational neuroscience.