MicroRNA-204-5p reduction in rat hippocampus contributes to stress-induced pathology via targeting RGS12 signaling pathway.
MicroRNA-204-5p reduction in rat hippocampus contributes to stress-induced pathology via targeting RGS12 signaling pathway.
复制标题
大鼠海马中 MicroRNA-204-5p 的减少通过靶向 RGS12 信号通路导致应激诱发的病理学
DOI：
10.1186/s12974-021-02299-5
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发表时间：
2021-10-21
影响因子：
9.3
通讯作者：
Yu SY
中科院分区：
文献类型：
--
作者：
Lan T;Li Y;Fan C;Wang L;Wang W;Chen S;Yu SY
背景神经炎症在包括抑郁症在内的大多数神经系统疾病的发病机制中占有重要地位。然而，与抑郁症中神经元损伤相关的神经炎症的潜在分子机制在很大程度上仍不清楚。因此，确定潜在的分子机制和治疗目标将有助于更好地了解这种condition.MethodsChronic不可预知的压力（CUS）的进展，用于诱导抑郁样行为的大鼠。RNA测序检测差异表达的microRNA。立体定向注射AAV病毒以过表达或敲低miR-204- 5 p。免疫印迹或免疫荧光法检测氧化标志物和炎症相关蛋白。氧化应激酶和产物使用酶联试剂盒进行验证。电镜观察突触形态及超微结构变化。结果慢性应激后大鼠海马齿状回（DG）区miR-204- 5 p表达显著下调，并伴有氧化应激引起的DG区神经元损伤。相比之下，miR-204- 5 p在CUS大鼠DG区域内的过表达通过直接靶向G蛋白信号传导调节因子12（RGS 12）减轻了氧化应激和神经炎症，这种作用伴随着这些CUS大鼠中抑郁样行为的改善。此外，下调miR-204- 5 p可诱导DG区神经元功能恶化和大鼠抑郁样行为的发生。ConclusionTogether，这些结果表明，miR-204- 5 p在调节氧化应激损伤中起关键作用。这些发现为miR-204- 5 p参与与抑郁表型相关的氧化应激机制提供了证据。
BackgroundNeuroinflammation occupies a pivotal position in the pathogenesis of most nervous system diseases, including depression. However, the underlying molecular mechanisms of neuroinflammation associated with neuronal injury in depression remain largely uncharacterized. Therefore, identifying potential molecular mechanisms and therapeutic targets would serve to better understand the progression of this condition.MethodsChronic unpredictable stress (CUS) was used to induce depression-like behaviors in rats. RNA-sequencing was used to detect the differentially expressed microRNAs. Stereotactic injection of AAV virus to overexpress or knockdown the miR-204-5p. The oxidative markers and inflammatory related proteins were verified by immunoblotting or immunofluorescence assay. The oxidative stress enzyme and products were verified using enzyme-linked assay kit. Electron microscopy analysis was used to observe the synapse and ultrastructural pathology. Finally, electrophysiological recording was used to analyze the synaptic transmission.ResultsHere, we found that the expression of miR-204-5p within the hippocampal dentate gyrus (DG) region of rats was significantly down-regulated after chronic unpredicted stress (CUS), accompanied with the oxidative stress-induced neuronal damage within DG region of these rats. In contrast, overexpression of miR-204-5p within the DG region of CUS rats alleviated oxidative stress and neuroinflammation by directly targeting the regulator of G protein signaling 12 (RGS12), effects which were accompanied with amelioration of depressive-like behaviors in these CUS rats. In addition, down-regulation of miR-204-5p induced neuronal deterioration in DG regions and depressive-like behaviors in rats.ConclusionTaken together, these results suggest that miR-204-5p plays a key role in regulating oxidative stress damage in CUS-induced pathological processes of depression. Such findings provide evidence of the involvement of miR-204-5p in mechanisms underlying oxidative stress associated with depressive phenotype.Graphical Abstract
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影响因子：
10.6
作者：
Miller, Andrew H.;Maletic, Vladimir;Raison, Charles L.
通讯作者：
Raison, Charles L.
影响因子：
16
作者：
Bidinosti M;Ran I;Sanchez-Carbente MR;Martineau Y;Gingras AC;Gkogkas C;Raught B;Bramham CR;Sossin WS;Costa-Mattioli M;DesGroseillers L;Lacaille JC;Sonenberg N
通讯作者：
Sonenberg N
影响因子：
4.4
作者：
Gulyaeva, Natalia V.
通讯作者：
Gulyaeva, Natalia V.
影响因子：
5.3
作者：
Jimenez-Fernandez, Sara;Gurpegui, Manuel;Correll, Christoph U.
通讯作者：
Correll, Christoph U.
影响因子：
11.4
作者：
Cobley JN;Fiorello ML;Bailey DM
通讯作者：
Bailey DM