ESTROGEN REGULATES CYTOKINE EXPRESSION IN THE CEREBELLUM

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们拟研究雌激素与衰老雌性大鼠小脑巨噬细胞（小胶质细胞）的关系。运动能力随着年龄的增长而下降，这表明小脑细胞的早变性对运动结构有长期影响。小胶质细胞是炎症细胞因子的丰富来源，当被激活时，在病理条件下已被证明。然而，雌激素以及一些细胞因子（如IL-6）对大脑的作用是增强突触可塑性和记忆巩固。虽然小脑传统上不被认为是雌激素反应区，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显微镜，我们将使用小胶质细胞标记OX-42和细胞因子标记il - α、- β、IL-6和TNF α来识别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有关。我们将确定年龄相关的雌激素缺失是否会导致小脑小胶质细胞迁移和/或增殖潜能的降低，以及它是否会调节在老年大鼠小胶质细胞中发现的细胞因子阳性细胞的表达。其基本原理是，由于我们知道雌激素可以作为免疫保护剂，与年龄相关的雌激素缺失可能导致小脑小胶质细胞中细胞因子受体的上调，从而引发可能影响小脑功能的反应。更重要的是，我们的目标是对标记的小胶质细胞和那些可能表达细胞因子的细胞的数量和形态特征进行有效、精确、无偏倚和可靠的估计。神经生物学和计算机的结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.