Changes in gene expression after lipopolysaccharide-induced neuroinflammation

脂多糖诱导的神经炎症后基因表达的变化

• 批准号: 7732147
• 负责人: Francesca Bosetti
• 金额: $ 31.21万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732147
• 关键词: Acute; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animals; Behavioral; Brain; CD14 gene; Cerebral cortex; Cessation of life; Cognitive deficits; Condition; Cytoskeletal Modeling; Cytoskeletal Proteins; Disease; Dose; Gene Expression; Genes; Gram-Negative Bacteria; Growth; Hippocampus (Brain); Hour; Immune system; Immunocompetent; Individual; Infection; Inflammation; Inflammatory; Injection of therapeutic agent; Learning; Lipopolysaccharides; Long-Term Potentiation; Memory; Messenger RNA; Microarray Analysis; Microglia; Mus; Neuraxis; Neurons; Numbers; Ontology; Parkinson Disease; Play; Proteins; Role; Thinking; Transcript; brain cell; chemokine; cognitive change; cytokine; interest; lateral ventricle; migration; nervous system development; neuroinflammation; normal aging; object recognition; response; synaptogenesis; toll-like receptor 4

A single intracerebroventricular injection of LPS was administered into the lateral ventricle of a mouse and, 24 hours later, gene expression was examined in the cerebral cortex and hippocampus using microarray technology. Gene set analysis showed that gene ontology (GO) terms for inflammation, cytokine activity, chemokine activity, and cytoskeletal reorganization, were significantly enriched 24 hours following the injection, whereas GO terms associated with nervous system development, neuron migration, synaptogenesis, and learning and memory showed decreased expression. Using strict criteria for individual genes, we detected 224 changed transcripts in the cortex and 170 in the hippocampus. Notably, expression of early growth response 1 (Egr1, also Zif268) and activity regulated cytoskeletal protein (Arc) mRNA were significantly lower in the cortex of LPS-treated animals. These effects are of interest because the protein products of Egr1 and Arc are induced during, and are required for, the consolidation of memory; reduced expression of these genes therefore may underlie some of the electrophysiological, behavioral, and cognitive changes observed in experimental neuroinflammation and in diseases with a marked neuroinflammatory component.

在小鼠的外侧心室中施用了单个脑室内注射LPS，24小时后，使用微阵列技术在脑皮质和海马中检查了基因表达。 基因组分析表明，注射后24小时24小时对炎症，细胞因子活性，趋化因子活性和细胞骨架重组的术语显着富集，而GO术语与神经系统发育，神经元迁移，突触，学习和记忆相关。 使用严格的单个基因标准，我们检测到皮质中224个变化的转录本，海马中有170个变性。 值得注意的是，在LPS处理的动物的皮质中，早期生长反应1（EGR1，也是ZIF268）和活性调节的细胞骨架蛋白（ARC）mRNA的表达显着降低。 这些效果很有趣，因为在记忆的巩固过程中，EGR1和ARC的蛋白质产物是诱导的。因此，这些基因的表达降低可能是在实验性神经炎症和具有明显神经炎症成分的疾病中观察到的一些电生理，行为和认知变化的基础。