Brain and Spinal Injury Center, University of California San Francisco, San Francisco, CA 94110, USA.
Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S39-49. doi: 10.1016/j.bbi.2011.02.003. Epub 2011 Feb 12.
Neurons exist within a microenvironment that significantly influences their function and survival. While there are many environmental factors that can potentially impact neuronal function, activation of the innate immune system (microglia) is an important element common to many neurological and pathological conditions associated with memory loss. Learning and memory processes rely on the ability of neurons to alter their transcriptional programs in response to synaptic input. Recent advances in cell-based imaging of plasticity-related immediate-early gene (IEG) expression have provided a tool to investigate plasticity-related changes across multiple brain regions. The activity-regulated, cytoskeleton-associated IEG Arc is a regulator of protein synthesis-dependent forms of synaptic plasticity, which are essential for memory formation. Visualisation of Arc provides cellular level resolution for the mapping of neuronal networks. Chronic activation of the innate immune system alters Arc activity patterns, and this may be a mechanism by which it induces the cognitive dysfunction frequently associated with neuroinflammatory conditions. This review discusses the use of Arc expression during activation of the innate immune system as a valid marker of altered plasticity and a predictor of cognitive dysfunction.
神经元存在于一个微环境中，这个微环境对其功能和存活有重大影响。虽然有许多环境因素可能潜在地影响神经元功能，但固有免疫系统（小胶质细胞）的激活是与记忆丧失相关的许多神经和病理状况的共同重要因素。学习和记忆过程依赖于神经元根据突触输入改变其转录程序的能力。基于细胞的可塑性相关即时早期基因 (IEG) 表达的成像的最新进展为研究跨多个脑区的可塑性相关变化提供了工具。活性调节的细胞骨架相关 IEG Arc 是突触可塑性的蛋白质合成依赖性形式的调节剂，对记忆形成至关重要。Arc 的可视化提供了神经元网络映射的细胞水平分辨率。固有免疫系统的慢性激活改变了 Arc 的活性模式，这可能是其引发与神经炎症状况经常相关的认知功能障碍的一种机制。这篇综述讨论了固有免疫系统激活期间 Arc 表达作为改变的可塑性的有效标志物和认知功能障碍的预测因子的用途。
