基因决定的神经退行性变易感性与炎症基因的表达相关。

Genetically determined susceptibility to neurodegeneration is associated with expression of inflammatory genes.

作者信息

Swanberg Maria, Duvefelt Kristina, Diez Margarita, Hillert Jan, Olsson Tomas, Piehl Fredrik, Lidman Olle

机构信息

Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, CMM, L8:04, Karolinska University Hospital Solna, SE-17176, Stockholm, Sweden.

出版信息

Neurobiol Dis. 2006 Oct;24(1):67-88. doi: 10.1016/j.nbd.2006.05.016. Epub 2006 Aug 23.

DOI:10.1016/j.nbd.2006.05.016

PMID:16934480

Abstract

Axonal damage, a core feature of neurological diseases, induces a retrograde reaction in neurons and surrounding glia. We determined transcriptional profiles of this reaction using Affymetrix oligonucleotide arrays. Gene expression was examined in spinal cord tissue prior to injury and following ventral root avulsion in two inbred rat strains, where the degree of neurodegeneration differs. Stringent statistical analysis revealed 278 regulated genes, whereof 245 were regulated by the injury and 68 differed between strains. Principal component analysis disclosed a common injury response pattern significantly modified by genetic background. Notably, inflammatory genes comprised the largest group of genes induced by injury and these transcripts prevailed in the strain most susceptible to neurodegeneration. In addition, levels of the strain regulated genes C1qb and Timp1 correlated with degree of neurodegeneration in a cohort of genetically heterogeneous animals. These results suggest a link between the inflammatory response elicited by nerve injury and subsequent neurodegeneration.

摘要

轴突损伤是神经疾病的一个核心特征，可在神经元和周围神经胶质细胞中引发逆行反应。我们使用Affymetrix寡核苷酸阵列确定了这种反应的转录谱。在两种近交系大鼠中，研究了损伤前和腹根撕脱后脊髓组织中的基因表达，这两种大鼠的神经退行性变程度不同。严格的统计分析揭示了278个受调控的基因，其中245个受损伤调控，68个在品系间存在差异。主成分分析揭示了一种常见的损伤反应模式，该模式因遗传背景而有显著改变。值得注意的是，炎症基因是损伤诱导的最大基因群，这些转录本在最易发生神经退行性变的品系中占主导地位。此外，在一组基因异质的动物中，品系调控基因C1qb和Timp1的水平与神经退行性变程度相关。这些结果表明神经损伤引发的炎症反应与随后的神经退行性变之间存在联系。