micro RNA expression analysis in the prefrontal cortex of Fkbp5 deficient mice

Psychological stress is a risk factor for several diseases. In particular, stressor exposure has been linked with various psychiatric disorders. Since the hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the regulation of stress responses, it has been implicated in the etiology of stress related disorders such as PTSD. The HPA axis regulate synthesis and release of glucocorticoids and its dysregulation cause abnormal response to stress. FK506-binding protein 51 (FKBP5) is a co chaperone of HSP90 in the glucocorticoid receptor (GR) molecular complex and a key regulator of the sensitivity of GR. In this study, we profiled the miRNAs in the prefrontal cortex of FKBP5 knock out mice compared to the wild type. Subsequently, we profiled target mRNAs for differentially expressed miRNAs in the FKBP5 deficient mice using several tools for sequence-based miRNA target prediction such as miRDB, DIANA tool, miRmap and TargetScan. Gene ontology analysis suggested that differentially expressed miRNAs in the brain of FKBP5 deficient mice may be involved in neuron development, cell motion, endocytosis, and cell-cell adhesion. These results suggest that Nfasc could be a new target for understanding of the pathophysiology of PTSD. miRNA profiles of prefrontal cortex (PFC) from wild type and Fkbp5 deficient mice were generated by small RNA sequencing using Illumina HiSeq 2500.心理应激是多种疾病的危险因素。具体而言，应激暴露与多种精神障碍存在关联。由于下丘脑-垂体-肾上腺（HPA）轴在应激反应的调控中发挥核心作用，其与创伤后应激障碍（PTSD）等应激相关障碍的病因学密切相关。HPA轴可调控糖皮质激素的合成与释放，其功能失调会引发异常应激应答。FK506结合蛋白51（FKBP5）是糖皮质激素受体（GR）分子复合物中热休克蛋白90（HSP90）的共伴侣蛋白，同时是调控GR敏感性的关键因子。本研究对FKBP5基因敲除小鼠与野生型小鼠的前额叶皮层microRNA（miRNA）表达谱进行了分析。随后，本研究借助miRDB、DIANA tool、miRmap及TargetScan等基于序列的miRNA靶标预测工具，对FKBP5缺陷小鼠中差异表达miRNA的靶mRNA开展了预测分析。基因本体分析结果显示，FKBP5缺陷小鼠脑组织内的差异表达miRNA可能参与神经元发育、细胞运动、内吞作用及细胞间黏附等生物学过程。本研究结果提示，Nfasc或可成为阐释创伤后应激障碍病理生理学机制的全新靶点。本研究通过Illumina HiSeq 2500平台开展小RNA测序，获取了野生型与FKBP5缺陷小鼠前额叶皮层（PFC）的miRNA表达谱。