Transcriptome-wide changes in the Substantia Nigra following Deep Brain Stimulation in the Subthalamic Nuecleus of a PD rat model.

In this study we identify the gene espression changes that occur in the substantia nigra in a Parkinson's Disease (PD) rat model with and without deep brain stimulation (DBS). A rat model of PD was created as previously described by stereotacticaly injecting an AAV-expressing the human A53T_mutated form of a-Synuclein into the Substantia Nigra of adult rats, while control rats were injected with empty vector (EV). These mice exhibit neurodegeneration in the Substantia Nigra and Parkinson-like behaviour phenotypes. Sixteen weeks after the injection, RNA was isolated from the Substantia Nigra and Striatum. Single-end 75nt high throughput sequencing were performed on libraries prepared from the RNA. We identified over 200 genes that were differentially expressed between control and Parkinson's ratswith a log2 fold-change > |0.6|. These genes were enriched for terms related to immune activation. The genes associated with these GO terms tended to be up-regulated in the Parkinson's rats suggesting that brain-localized immune cells are more activated in Parkinson's disease. Interestingly in the rats treated with DBS, these immune-related genes were comparable to control animals.本研究旨在明确脑深部电刺激（deep brain stimulation, DBS）干预与非干预条件下，帕金森病（Parkinson's Disease, PD）大鼠模型黑质内发生的基因表达变化。如既往研究所述，通过立体定向注射携带人源A53T突变型α-突触核蛋白（α-Synuclein）的腺相关病毒（adeno-associated virus, AAV）至成年大鼠黑质，构建PD大鼠模型；对照组大鼠则注射空载体（empty vector, EV）。该模型大鼠可出现黑质神经退行性变及类帕金森病行为表型。造模后第16周，研究人员从大鼠黑质与纹状体（Striatum）中分离总RNA，并对制备的RNA文库开展单端75nt高通量测序。本研究鉴定得到200余个在对照组与PD大鼠间存在差异表达的基因，其对数2倍变化（log2 fold-change）绝对值大于0.6。富集分析结果显示，这些基因显著富集于与免疫激活相关的功能术语。与这些基因本体（Gene Ontology, GO）术语相关的基因在PD大鼠中多呈上调表达，提示脑内驻留免疫细胞在帕金森病中的激活程度更高。值得注意的是，接受DBS干预的大鼠中，此类免疫相关基因的表达水平与对照组动物基本相当。