Hippocampus miRNA profiles in chronic cerebral-hypoperfusion rats

Chronic cerebral hypoperfusion (CCH) is a well-known risk factor for vascular dementia and other neurodegenerative disease, for which there are currently no effective medications available. MicroRNA (miRNA) are noncoding RNAS mediating post-translational silencing of genes, and has been extensively studied for their involvement in neurodegenerative disease. However, little is known about their roles in vascular dementia (VaD). In this work, a bilateral common carotid arteries occlusion (2-VO) surgery in rats was employed to induced CCH related cognitive dysfunction. Four months later, the hippocampi were dissected from 2-VO and sham operated rats for high-throughput profiling of miRNAs. Twelve differentially expressed miRNAs were identified according to a cutoff of |log2(Fold Change)|≥1 and p＜0.05. GO analysis of target genes revealed that the most relevant biological processes included the regulatory region nucleic acid binding, histone acetyltransferase binding, organic acid transmembrane transporter activity, L-amino acid transmembrane transporter activity. The cellular structure mainly included histone deacetylation complexes, endosomes, Golgi membranes, etc. And the involved molecular processes mainly included axon development, organ morphogenesis, macromolecular modification, regulation of neuron projection development, neuron development. This study provides a framework for understanding the alternations in hippocampus miRNA profiles underwent hypoxia insult.慢性脑低灌注（Chronic cerebral hypoperfusion, CCH）是血管性痴呆及其他神经退行性疾病的公认危险因素，目前针对该类病症尚无有效治疗药物。微小RNA（MicroRNA, miRNA）是一类介导基因翻译后沉默的非编码RNA，已被广泛研究其在神经退行性疾病中的作用，但关于其在血管性痴呆（Vascular dementia, VaD）中的功能却鲜有报道。本研究采用大鼠双侧颈总动脉结扎（2-Vessel Occlusion, 2-VO）手术构建CCH相关认知功能障碍模型。造模4个月后，分别从2-VO模型组与假手术组大鼠体内分离海马组织，开展miRNA高通量表达谱分析。按照|log₂(倍数变化)|≥1且p值＜0.05的截断标准，共筛选得到12个差异表达miRNA。对其靶基因进行基因本体（Gene Ontology, GO）富集分析结果显示：富集度最高的生物学过程包括调控区域核酸结合、组蛋白乙酰转移酶结合、有机酸跨膜转运体活性、L-氨基酸跨膜转运体活性；主要富集的细胞组分包括组蛋白去乙酰化复合物、内体、高尔基体膜等；涉及的分子过程主要包括轴突发育、器官形态发生、大分子修饰、神经元投射发育调控以及神经元发育。本研究为解析低氧损伤后海马组织miRNA表达谱的变化提供了研究框架。