STUDIES OF A MOUSE MODEL OF ALS-PDC

ALS-PDC小鼠模型的研究

• 批准号: 7369582
• 负责人: CHRISTOPHER Ariel SHAW
• 金额: $ 0.58万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369582
• 关键词: STUDIES; MOUSE; MODEL; ALS; PDC

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. Exposure to cycad (Cycas micronesica K.D. Hill) toxins via diet has been shown to induce neurodegeneration in vivo that mimics the progressive neurological disease, ALS-parkinsonism dementia complex (ALS-PDC). In previous studies, specific cortical and subcortical cell loss was measured with conventional stained sections. We have examined the utility of magnetic resonance (MR) microscopy was used to examine neurodegeneration in 3D in the isolated intact brain and spinal cord. Mice were fed washed cycad for 2 months and showed progressive motor deficits resembling human ALS-PDC. Animals were perfused and CNS tissue was imaged at 17.6 Tesla. T2* scans were conducted on both spinal cord and brain samples with an isotropic resolution of 41 mm. Cycad-fed mice showed significantly decreased volumes in lumbar spinal cord gray matter, substantia nigra, striatum, basal nucleus/internal capsule, and olfactory bulb. Cortical measurements revealed that cycad-fed mice also showed decreased cortical thickness. These results show that MR microscopy is sensitive enough to measure degeneration in this early stage model of a progressive neurological disease, and may be applicable in vivo on the same model. Similar analysis may be used in the future as a diagnostic aid in tracking the early progression of neurological disorders in pre-clinical human subjects. Studies are underway to evaluate the utility of DTI to examine the same brain tissue and detect deformities. We have also begun similar examinations on spinal cord samples from the same animals.

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。暴露于苏铁（Cycas micronesica K.D.）Hill）毒素通过饮食诱导体内神经变性，其模拟进行性神经系统疾病ALS-帕金森痴呆综合征（ALS-PDC）。在以前的研究中，特定的皮质和皮质下细胞损失是用常规染色切片测量的。我们已经研究了磁共振（MR）显微镜的实用性，用于检查神经退行性变的3D在孤立的完整的大脑和脊髓。给小鼠喂食洗涤的苏铁2个月，并显示出类似于人ALS-PDC的进行性运动缺陷。对动物进行灌注，并在17.6特斯拉下对CNS组织进行成像。T2* 扫描进行了脊髓和大脑样本的各向同性分辨率为41毫米。苏铁喂养的小鼠表现出显着减少量在腰脊髓灰质，黑质，纹状体，基底核/内囊，和嗅球。皮质测量显示，苏铁喂养的小鼠也表现出皮质厚度减少。这些结果表明，MR显微镜足够灵敏，可以测量进行性神经系统疾病早期模型的变性，并且可能适用于体内相同模型。类似的分析将来可能会用作跟踪临床前人类受试者神经系统疾病早期进展的诊断辅助手段。研究正在进行中，以评估DTI检查相同的脑组织和检测畸形的效用。我们还开始对同一动物的脊髓样本进行类似的检查。