Chuvakova Lyubov N, Funikov Sergei Yu, Rezvykh Alexander P, Davletshin Artem I, Evgen'ev Michael B, Litvinova Svetlana A, Fedotova Irina B, Poletaeva Inga I, Garbuz David G
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
Front Mol Neurosci. 2021 Nov 4;14:738930. doi: 10.3389/fnmol.2021.738930. eCollection 2021.
Audiogenic epilepsy (AE), inherent to several rodent strains is widely studied as a model of generalized convulsive epilepsy. The molecular mechanisms that determine the manifestation of AE are not well understood. In the present work, we compared transcriptomes from the in the midbrain zone, which are crucial for AE development, to identify genes associated with the AE phenotype. Three rat strains without sound exposure were compared: Krushinsky-Molodkina (KM) strain (100% AE-prone); Wistar outbred rat strain (non-AE prone) and "0" strain (partially AE-prone), selected from F2 KM × Wistar hybrids for their lack of AE. The findings showed that the KM strain gene expression profile exhibited a number of characteristics that differed from those of the Wistar and "0" strain profiles. In particular, the KM rats showed increased expression of a number of genes involved in the positive regulation of the MAPK signaling cascade and genes involved in the positive regulation of apoptotic processes. Another characteristic of the KM strain which differed from that of the Wistar and "0" rats was a multi-fold increase in the expression level of the gene and a significant decrease in the expression of the gene. Decreased expression of a number of oxidative phosphorylation-related genes and a few other genes was also identified in the KM strain. Our data confirm the complex multigenic nature of AE inheritance in rodents. A comparison with data obtained from other independently selected AE-prone rodent strains suggests some common causes for the formation of the audiogenic phenotype.
听源性癫痫（AE）是几种啮齿动物品系所固有的，作为全身性惊厥性癫痫的模型被广泛研究。决定AE表现的分子机制尚未完全了解。在本研究中，我们比较了对AE发展至关重要的中脑区域的转录组，以鉴定与AE表型相关的基因。比较了三只未接受声音刺激的大鼠品系：克鲁申斯基-莫洛迪纳（KM）品系（100%易患AE）；远交系Wistar大鼠品系（不易患AE）和“0”品系（部分易患AE），“0”品系是从F2代KM×Wistar杂种中因其缺乏AE而挑选出来的。研究结果表明，KM品系的基因表达谱呈现出一些与Wistar和“0”品系不同的特征。特别是，KM大鼠显示出一些参与MAPK信号级联正调控的基因以及参与凋亡过程正调控的基因表达增加。KM品系与Wistar和“0”大鼠不同的另一个特征是 基因表达水平增加了数倍，而 基因的表达显著降低。在KM品系中还发现一些氧化磷酸化相关基因和其他一些基因的表达降低。我们的数据证实了啮齿动物中AE遗传的复杂多基因性质。与从其他独立选择的易患AE的啮齿动物品系获得的数据进行比较，提示了听源性表型形成的一些共同原因。
