IMMUNOPATHOLOGIC ALTERATIONS IN RHESUS MACAQUES WITH GLOBOID CELL LEUKODYSTROPHY

患有球状细胞脑白质营养不良的恒河猴的免疫病理学改变

• 批准号: 8358070
• 负责人: Bruce A. Bunnell
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358070
• 关键词: Affect; Age; Animals; Astrocytes; Brain; CCL2 gene; Cells; Data; Disease; Disease Progression; Funding; Gene Expression; Glial Fibrillary Acidic Protein; Globoid cell leukodystrophy; Grant; Inflammatory; Interleukin-1; Macaca; Macaca mulatta; Messenger RNA; Microglia; National Center for Research Resources; Peripheral Nervous System; Play; Primates; Principal Investigator; Process; Research; Research Infrastructure; Resources; Role; Sampling; Source; Staging; Therapeutic Intervention; Toll-like receptors; Tumor Necrosis Factor-alpha; United States National Institutes of Health; cost; cytokine; galactosylceramidase; human TNF protein; mind control; sex; synthetic polymer Bioplex; white matter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 from unaffected animals. In addition, we have begun studies to investigate the role of the inflammatory processes on disease progression. We have generated data demonstrating a wave of altered expression of the Toll-like Receptors (TLRs) in the Krabbe brain. The altered expression correlates with the progression of the disease. It is hoped that this analysis will provide an in depth analysis in to the role that the inflammatory process plays in the disease progression and to identify potential targets for therapeutic intervention.

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