Transcriptomic Responses to Prion Disease in Rats

While prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular.尽管朊病毒（prion）感染已在实验小鼠中得到广泛表征，但学界对其他啮齿类动物应对朊病毒的分子反应仍所知甚少。为探究此类反应并开展对比研究，我们通过连续传代小鼠RML朊病毒，在实验大鼠中诱导出朊病毒疾病。本研究中我们描述了大鼠体内朊病毒的积累与相关病理特征，并阐明了整个朊病毒疾病进程中的转录组影响。对实验小鼠与大鼠的转录组对比分析显示，二者在应对朊病毒感染时激活了相似的分子过程。然而，在单个转录本层面，小鼠与大鼠之间存在差异：许多在小鼠痒病中失调的基因在大鼠体内并未受到影响。尽管存在这些差异，感染痒病的小鼠与大鼠之间仍存在诸多保守的转录组反应。我们的研究结果凸显了比较研究方法在理解神经退行性疾病，尤其是朊病毒疾病方面的应用价值。