Department of Biology, Aging Mind and Brain Initiative, 143 Biology Building East, 338 BBE, University of Iowa, Iowa City, IA 52242, USA.
Sci Signal. 2017 Oct 17;10(501):eaan4893. doi: 10.1126/scisignal.aan4893.
Learning, a process by which animals modify their behavior as a result of experience, enables organisms to synthesize information from their surroundings to acquire resources and avoid danger. We showed that a previous encounter with only the odor of pathogenic bacteria prepared to survive exposure to the pathogen by increasing the heat shock factor 1 (HSF-1)-dependent expression of genes encoding molecular chaperones. Experience-mediated enhancement of chaperone gene expression required serotonin, which primed HSF-1 to enhance the expression of molecular chaperone genes by promoting its localization to RNA polymerase II-enriched nuclear loci, even before transcription occurred. However, HSF-1-dependent chaperone gene expression was stimulated only if and when animals encountered the pathogen. Thus, learning equips to better survive environmental dangers by preemptively and specifically initiating transcriptional mechanisms throughout the whole organism that prepare the animal to respond rapidly to proteotoxic agents. These studies provide one plausible basis for the protective role of environmental enrichment in disease.
学习是动物通过经验改变其行为的过程,使生物体能够从周围环境中综合信息,以获取资源和避免危险。我们表明,仅通过接触致病性细菌的气味,就可以预先准备好通过增加热休克因子 1 (HSF-1) 依赖性分子伴侣基因的表达来存活于病原体暴露之下。经验介导的伴侣蛋白基因表达增强需要血清素,它通过促进 HSF-1 定位到富含 RNA 聚合酶 II 的核位来增强分子伴侣基因的表达,甚至在转录发生之前。然而,只有当动物遇到病原体时,HSF-1 依赖性伴侣蛋白基因表达才会受到刺激。因此,学习使动物能够通过预先和专门地启动整个生物体中的转录机制来更好地应对环境危险,从而准备动物快速应对蛋白毒性物质。这些研究为环境富集在疾病中的保护作用提供了一个合理的基础。