Department of Neurology, Maternal and Child Health Hospital of Weifang Medical University, Weifang, 261011, China.
Department of Clinical Lab, Maternal and Child Health Hospital of Weifang Medical University, Weifang, 261011, China.
Sci Rep. 2021 Jan 13;11(1):1262. doi: 10.1038/s41598-020-79543-0.
Febrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.
热性惊厥 (FSs) 是婴儿和儿童中常见的神经紊乱，尽管确切的潜在机制仍有待探索，特别是在 microRNAs (miRNAs) 的表达模式和功能方面。在本报告中，我们旨在通过 Synaptojanin-1 (SYNJ1) 筛选新的潜在 miRNAs，并研究 FS 大鼠海马神经元中 miR-148a-3p 的作用。30 只大鼠随机分为正常组和 FS 模型组，通过 miRNA 芯片进行研究。该过程鉴定出 31 个差异表达（20 个上调和 11 个下调）的 miRNAs 和潜在的 miRNA 靶基因。此外，将海马神经元分为五组进行不同的转染。通过 TUNEL 和流式细胞术检测细胞凋亡。SYNJ1 被鉴定为 miR-148-3p 的靶基因。体外实验表明，抑制 miR-148a-3p 可减少神经元细胞凋亡。此外，miR-148a-3p 的过表达激活了 PI3K/Akt 信号通路并导致海马神经元凋亡。miR-148a-3p 抑制剂可以逆转上述事件。总之，我们的数据表明 FS 大鼠模型的海马 miRNA 表达谱提供了大量候选 miRNAs 和神经元相关靶基因的数据库。此外，miR-148a-3p 通过激活 SYNJ1/PI3K/Akt 信号通路作为凋亡增强剂发挥作用，为治疗高热诱导的脑损伤的婴儿提供了潜在的治疗靶点。
