BACKGROUNDS Recently, extensive evidence has indicated that the biological role of long non-coding RNAs (lncRNAs) in neurodegenerative diseases is becoming increasingly evident. The lncRNA brain-derived neurotrophic factor anti-sense (BDNF-AS) has been found to be dysregulated in Huntington's Disease. However, the function of BDNF-AS in Parkinson's disease (PD) remains unknown. The purpose of this present study was to explore the effect of BDNF-AS on PD and its underlying molecular mechanisms. METHODS The MPTP-induced mouse model of PD and MPP+-induced SH-SY5Y cell model were established. Immunofluorescence was performed to determine the number of TH + positive cells. Mice behavioral changes were detected by pole and rota-rod test. SH-SY5Y cells viability, apoptosis was detected by MTT assay and flow cytometry. The number of autophagosome was measured by transmission electron microscopy. Dopamine content was tested by high performance liquid chromatography. Dual-luciferase reporter gene assay was utilized to verify the correlation between BDNF-AS and miR-125b-5p. qRT-PCR and western blot were used to detect gene expression levels. RESULTS Our results showed that BDNF-AS was up-regulated in MPTP-induced PD model and dopamine neurons, and MPP + treated SH-SY5Y cells, while miR-125b-5p was down-regulated. The expression of BDNF-AS was positively related with the MPP + concentration. BDNF-AS knockdown could significantly promote cell proliferation, while inhibit apoptosis and autophagy in SH-SY5Y cells treated by MPP + . Silencing BDNF-AS could also increase TH positive neurons and significantly suppress the autophagy of PD mice. Additionally, miR-125b-5p, a putative target gene of BDNF-AS, was involved in the effects of BDNF-AS on SH-SY5Y cell apoptosis and autophagy. CONCLUSIONS Our study demonstrated that knockdown of BDNF-AS could elevate SH-SY5Y cell viability, inhibit autophagy and apoptosis in MPTP-induced PD models through regulating miR-125b-5p, suggesting that BDNF-AS might act as a potential therapeutic target for PD.

中文翻译：

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LncRNA BDNF-AS 通过消融 microRNA-125b-5p 促进 MPTP 诱导的帕金森病中的自噬和细胞凋亡。

背景最近，大量证据表明，长链非编码 RNA (lncRNA) 在神经退行性疾病中的生物学作用正变得越来越明显。已发现 lncRNA 脑源性神经营养因子反义 (BDNF-AS) 在亨廷顿舞蹈症中失调。然而，BDNF-AS 在帕金森病 (PD) 中的功能仍然未知。本研究的目的是探讨 BDNF-AS 对 PD 的影响及其潜在的分子机制。方法建立MPTP诱导的PD小鼠模型和MPP+诱导的SH-SY5Y细胞模型。进行免疫荧光以确定TH + 阳性细胞的数量。通过极杆和旋转杆试验检测小鼠的行为变化。MTT法和流式细胞术检测SH-SY5Y细胞活力、凋亡。通过透射电子显微镜测量自噬体的数量。多巴胺含量通过高效液相色谱测试。双荧光素酶报告基因检测用于验证BDNF-AS和miR-125b-5p之间的相关性。qRT-PCR 和蛋白质印迹用于检测基因表达水平。结果 我们的结果表明，BDNF-AS 在 MPTP 诱导的 PD 模型和多巴胺神经元以及 MPP + 处理的 SH-SY5Y 细胞中上调，而 miR-125b-5p 下调。BDNF-AS的表达与MPP+浓度呈正相关。BDNF-AS 敲低可显着促进细胞增殖，同时抑制 MPP + 处理的 SH-SY5Y 细胞的凋亡和自噬。沉默BDNF-AS还可以增加TH阳性神经元并显着抑制PD小鼠的自噬。此外，miR-125b-5p，BDNF-AS 的推定靶基因，参与 BDNF-AS 对 SH-SY5Y 细胞凋亡和自噬的影响。结论 我们的研究表明敲低 BDNF-AS 可以通过调节 miR-125b-5p 提高 SH-SY5Y 细胞活力，抑制 MPTP 诱导的 PD 模型中的自噬和凋亡，表明 BDNF-AS 可能作为 PD 的潜在治疗靶点.