Department of Pharmacology, University of Washington, Seattle, Washington.
Hippocampus. 2010 Apr;20(4):492-8. doi: 10.1002/hipo.20646.
Activity-dependent changes in gene-expression are believed to underlie the molecular representation of memory. In this study, we report that in vivo activation of neurons rapidly induces the CREB-regulated microRNA miR-132. To determine if production of miR-132 is regulated by neuronal activity its expression in mouse brain was monitored by quantitative RT-PCR (RT-qPCR). Pilocarpine-induced seizures led to a robust, rapid, and transient increase in the primary transcript of miR-132 (pri-miR-132) followed by a subsequent rise in mature microRNA (miR-132). Activation of neurons in the hippocampus, olfactory bulb, and striatum by contextual fear conditioning, odor-exposure, and cocaine-injection, respectively, also increased pri-miR-132. Induction kinetics of pri-miR-132 were monitored and found to parallel those of immediate early genes, peaking at 45 min and returning to basal levels within 2 h of stimulation. Expression levels of primary and mature-miR-132 increased significantly between postnatal Days 10 and 24. We conclude that miR-132 is an activity-dependent microRNA in vivo, and may contribute to the long-lasting proteomic changes required for experience-dependent neuronal plasticity.
活动依赖性基因表达的改变被认为是记忆的分子基础。在这项研究中,我们报告说,神经元的体内激活会迅速诱导 CREB 调节的 microRNA miR-132。为了确定 miR-132 的产生是否受神经元活动的调节,我们通过定量 RT-PCR(RT-qPCR)监测其在小鼠脑中的表达。毛果芸香碱诱导的癫痫发作导致初级转录物 miR-132(pri-miR-132)的快速、短暂增加,随后成熟 microRNA(miR-132)增加。通过情景性恐惧条件反射、气味暴露和可卡因注射分别激活海马、嗅球和纹状体中的神经元也会增加 pri-miR-132。监测 pri-miR-132 的诱导动力学发现,其与早期基因的动力学平行,在刺激后 45 分钟达到峰值,在 2 小时内恢复到基础水平。初级和成熟 miR-132 的表达水平在出生后第 10 天至第 24 天显著增加。我们得出结论,miR-132 是体内一种活动依赖性的 microRNA,可能有助于经验依赖性神经元可塑性所需的持久蛋白质组变化。