Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Prion. 2012 Jul 1;6(3):282-301. doi: 10.4161/pri.19915.
Chronic wasting disease (CWD) is an invariably fatal neurologic disease that naturally infects mule deer, white tailed deer and elk. The understanding of CWD neurodegeneration at a molecular level is very limited. In this study, microarray analysis was performed to determine changes in the gene expression profiles in six different tissues including brain, midbrain, thalamus, spleen, RPLN and tonsil of CWD-infected elk in comparison to non-infected healthy elk, using 24,000 bovine specific oligo probes. In total, 329 genes were found to be differentially expressed (> 2.0-fold) between CWD negative and positive brain tissues, with 132 genes upregulated and 197 genes downregulated. There were 249 DE genes in the spleen (168 up- and 81 downregulated), 30 DE genes in the retropharyngeal lymph node (RPLN) (18 up- and 12 downregulated), and 55 DE genes in the tonsil (21 up- and 34 downregulated). Using Gene Ontology (GO), the DE genes were assigned to functional groups associated with cellular process, biological regulation, metabolic process, and regulation of biological process. For all brain tissues, the highest ranking networks for DE genes identified by Ingenuity Pathway Analysis (IPA) were associated with neurological disease, cell morphology, cellular assembly and organization. Quantitative real-time PCR (qRT-PCR) validated the expression of DE genes primarily involved in different regulatory pathways, including neuronal signaling and synapse function, calcium signaling, apoptosis and cell death and immune cell trafficking and inflammatory response. This is the first study to evaluate altered gene expression in multiple organs including brain from orally infected elk and the results will improve our understanding of CWD neurodegeneration at the molecular level.
慢性消瘦病（CWD）是一种会导致动物致命的神经系统疾病，它会自然感染骡鹿、白尾鹿和麋鹿。目前对于 CWD 神经退行性变的分子水平理解非常有限。在这项研究中，通过使用 24000 个牛特定的寡核苷酸探针，我们对来自感染和未感染 CWD 的麋鹿的大脑、中脑、丘脑、脾脏、咽后淋巴结和扁桃体等 6 种不同组织进行了微阵列分析，以确定 CWD 感染麋鹿的基因表达谱变化。结果发现，在 CWD 阴性和阳性脑组织之间有 329 个基因存在差异表达（>2.0 倍），其中 132 个基因上调，197 个基因下调。在脾脏中有 249 个差异表达基因（168 个上调和 81 个下调），在咽后淋巴结（RPLN）中有 30 个差异表达基因（18 个上调和 12 个下调），在扁桃体中有 55 个差异表达基因（21 个上调和 34 个下调）。使用基因本体论（GO），差异表达基因被分配到与细胞过程、生物调节、代谢过程和生物调节有关的功能组。对于所有脑组织，通过 IPA 鉴定的差异表达基因的最高排名网络与神经疾病、细胞形态、细胞组装和组织有关。定量实时 PCR（qRT-PCR）验证了主要涉及不同调节途径的差异表达基因的表达，包括神经元信号和突触功能、钙信号、细胞凋亡和细胞死亡以及免疫细胞迁移和炎症反应。这是第一项评估经口感染麋鹿的多个器官（包括大脑）中基因表达变化的研究，其结果将提高我们对 CWD 神经退行性变的分子水平的理解。
