IMMUNOPATHOLOGIC ALTERATIONS IN RHESUS MACAQUES WITH GLOBOID CELL LEUKODYSTROPHY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 球样细胞脑白质营养不良，或克拉伯病，是一种严重的中枢和外周神经系统疾病所造成的缺乏半乳糖苷酶（GALC）的活动。我们先前已经确定，受Krabbe病影响的恒河猴表现出显著增加的iNOS，TNF-α和IL-1的表达水平在受影响的白色物质，共定位与球状细胞，活化的小胶质细胞和星形胶质细胞。细胞因子的mRNA水平显示显着增加的基因表达的CCL 2在受影响的猕猴的大脑。在整个受影响的白色物质中检测到CCL 2表达细胞，与GFAP细胞和星形胶质细胞共定位。我们目前正在使用Bioplex分析在疾病进展的各个阶段进行细胞因子变化的完整分析。Krabbe脑白色物质样本直接与来自未受影响动物的年龄和性别匹配的对照脑样本进行比较。此外，我们已经开始研究炎症过程对疾病进展的作用。 希望这项分析能够深入了解炎症过程在疾病进展中的作用，并确定治疗干预的潜在靶点。

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. Globoid cell leukodystrophy, or Krabbe's disease, is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. We have previously determined that rhesus macaques affected with Krabbe's disease demonstrated marked increases in the levels of expression of iNOS, TNF-alpha, and IL-1 in the affected white matter, colocalizing with globoid cells, activated microglia, and astrocytes. Cytokine mRNA levels revealed markedly increased gene expression of CCL2 in the brain of affected macaques. CCL2-expressing cells were detected throughout the affected white matter, colocalizing with GFAP cells and astrocytes. We are presently performing as complete analysis of cytokine alterations using a Bioplex analysis at various stages of disease progression. Krabbe brain white matter samples are being directly compared to age and sex matched control brain samples form unaffected animals. In addition, we have begun studies to investigate the role of the inflammatory processes on disease progression. It is hoped that this analysis will provide insight into the role that the inflammatory process plays in the disease progression and to identify potential targets for therapeutic intervention.