Epileptogenesis Laboratory, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland.
Bioinformatics Laboratory, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland.
Sci Adv. 2020 Oct 9;6(41). doi: 10.1126/sciadv.aat5979. Print 2020 Oct.
Gene and protein expressions display circadian oscillations, which can be disrupted in diseases in most body organs. Whether these oscillations occur in the healthy hippocampus and whether they are altered in epilepsy are not known. We identified more than 1200 daily oscillating transcripts in the hippocampus of control mice and 1600 in experimental epilepsy, with only one-fourth oscillating in both conditions. Comparison of gene oscillations in control and epilepsy predicted time-dependent alterations in energy metabolism, which were verified experimentally. Although aerobic glycolysis remained constant from morning to afternoon in controls, it increased in epilepsy. In contrast, oxidative phosphorylation increased in control and decreased in epilepsy. Thus, the control hippocampus shows circadian molecular remapping, which is altered in epilepsy. We suggest that the hippocampus operates in a different functioning mode in epilepsy. These alterations need to be considered when studying epilepsy mechanisms, designing drug treatments, and timing their delivery.
基因和蛋白质表达呈现出昼夜节律波动，这种波动在大多数器官的疾病中都会被打乱。目前尚不清楚健康的海马体中是否存在这些波动，以及癫痫症中是否存在波动。我们在对照组小鼠的海马体中鉴定出了 1200 多个每日波动的转录本，在实验性癫痫症中鉴定出了 1600 个，其中只有四分之一在两种情况下都发生波动。对对照组和癫痫症中基因波动的比较预测了能量代谢的时变改变，这些改变在实验中得到了验证。尽管在对照组中，从早上到下午有氧糖酵解保持不变，但在癫痫症中它会增加。相比之下，氧化磷酸化在对照组中增加，在癫痫症中减少。因此，对照组的海马体显示出昼夜节律的分子重映射，而在癫痫症中则发生改变。我们认为，在癫痫症中，海马体以不同的功能模式运作。在研究癫痫症机制、设计药物治疗并确定其给药时间时，需要考虑这些改变。
