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帕金森病动物模型中脑室下区和齿状回的转录组分析

Transcriptome profiling of the subventricular zone and dentate gyrus in an animal model of Parkinson's disease.

作者信息

Bao Xin-Jie, Wang Geng-Chao, Zuo Fu-Xing, Li Xue-Yuan, Wu Jun, Chen Guo, Dou Wan-Chen, Guo Yi, Shen Qin, Wang Ren-Zhi

机构信息

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

State Key Laboratory of Medical Molecular Biology and Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

出版信息

Int J Mol Med. 2017 Sep;40(3):771-783. doi: 10.3892/ijmm.2017.3052. Epub 2017 Jul 3.

Abstract

Adult neurogenesis in the subventricular zone (SVZ), as well as in the subgranular zone contributes to brain maintenance and regeneration. In the adult brain, dopamine (DA) can regulate the endogenous neural stem cells within these two regions, while a DA deficit may affect neurogenesis. Notably, the factors that regulate in vivo neurogenesis in these subregions have not yet been fully characterized, particularly following DA depletion. In thi study, we performed RNA sequencing to investigate transcriptomic changes in the SVZ and dentate gyrus (DG) of mice in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This analysis identified differentially expressed genes which were involved in the regulation of transcription, immune response, extracellular region, cell junction and myelination. These genes partially displayed different temporal profiles of expression, some of which may participate in the metabolic switch related to neurogenesis. Additionally, the mitogen‑activated protein kinase (MAPK) signaling pathway was shown to be been positively regulated in the SVZ, while it was negatively affected in the DG following MPTP administration. Overall, our findings indicate that exposure to MPTP may exert different effects on transcriptome profiling between the SVZ and DG.

摘要

室管膜下区(SVZ)以及颗粒下区的成体神经发生有助于大脑的维持和再生。在成体大脑中,多巴胺(DA)可调节这两个区域内的内源性神经干细胞,而DA缺乏可能会影响神经发生。值得注意的是,调节这些亚区域体内神经发生的因素尚未完全明确,尤其是在DA耗竭后。在本研究中,我们进行了RNA测序,以研究小鼠的SVZ和齿状回(DG)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)反应的转录组变化。该分析确定了参与转录调控、免疫反应、细胞外区域、细胞连接和髓鞘形成的差异表达基因。这些基因部分呈现出不同的时间表达谱,其中一些可能参与与神经发生相关的代谢转换。此外,丝裂原活化蛋白激酶(MAPK)信号通路在SVZ中显示出正调控,而在给予MPTP后,DG中则受到负面影响。总体而言,我们的研究结果表明,暴露于MPTP可能对SVZ和DG之间的转录组谱产生不同影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0a/5547956/d995b45270a2/IJMM-40-03-0771-g00.jpg

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