State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China.
School of Medicine, Southeast University, Nanjing 210097, China.
Neurosci Lett. 2020 Jul 27;732:135074. doi: 10.1016/j.neulet.2020.135074. Epub 2020 May 22.
Parkinson's disease (PD) is the second most common neurodegenerative disease. However, the expression pattern and the differential gene in different brain regions and its functions remain unclear although many studies have been reported. In this present study, PD mouse model were build and four brain regions (cerebral cortex: CC, hippocampus: HP, striatum: ST, and cerebellum: CB) were separated for RNA-seq analysis. Results showed that different expressed genes were found between the different brain regions and more differential genes found in ST and HP when compared with control groups. Among them, Lrrk2, Mtor, Gxylt1, C920006o11Rik, Vdac1, Drd4, and Ncan showed the most significant to PD. PDCC vs. PDHP, PDHP vs. PDST and PDCC vs. PDST groups have 334, 722 and 495 differentially expressed genes (DEGs), respectively. Functional analyses results showed that the differential genes mainly related with posttranscriptional regulation of gene expression and protein localization to organelle and so on, which involved in AMPK, PI3K-Akt signaling pathway, and GABA-ergic synapse. Network biology analysis showed LRRK2, DRD2, IGF-1, GNAI1, GNAI3, PRKACA, PPP2R5C, and PIK3R1 play a major role in protein regulation of PD. Therefore, HP and ST play more important roles in the development of PD and it is also suggested the potential target gene for diagnosis and treatment of PD.
帕金森病（PD）是第二常见的神经退行性疾病。然而，尽管已经有许多研究报道，但不同脑区的表达模式和差异基因及其功能仍不清楚。在本研究中，构建了 PD 小鼠模型，并分离了四个脑区（大脑皮层：CC、海马：HP、纹状体：ST 和小脑：CB）进行 RNA-seq 分析。结果表明，不同脑区之间存在差异表达基因，与对照组相比，ST 和 HP 中发现的差异基因更多。其中，Lrrk2、Mtor、Gxylt1、C920006o11Rik、Vdac1、Drd4 和 Ncan 与 PD 相关性最大。PDCC 与 PDHP、PDHP 与 PDST 和 PDCC 与 PDST 组分别有 334、722 和 495 个差异表达基因（DEGs）。功能分析结果表明，差异基因主要与基因表达的转录后调控和蛋白质向细胞器的定位等有关，涉及 AMPK、PI3K-Akt 信号通路和 GABA 能突触。网络生物学分析表明，LRRK2、DRD2、IGF-1、GNAI1、GNAI3、PRKACA、PPP2R5C 和 PIK3R1 在 PD 的蛋白质调节中起主要作用。因此，HP 和 ST 在 PD 的发展中起着更重要的作用，这也提示了 PD 诊断和治疗的潜在靶基因。
