Department of Physiology, School of Basic Medical Sciences, Shandong University, 44 Wenhuaxilu Road, Jinan, Shandong, 250012, People's Republic of China.
Morphological Experimental Center, School of Basic Medical Sciences, Shandong University, 44 Wenhuaxilu Road, Jinan, Shandong, 250012, People's Republic of China.
J Neuroinflammation. 2021 Oct 21;18(1):243. doi: 10.1186/s12974-021-02299-5.
Neuroinflammation 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.
Chronic 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.
Here, 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.
Taken 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.
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据核心地位。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未得到阐明。因此，确定潜在的分子机制和治疗靶点将有助于更好地理解这种疾病的进展。
采用慢性不可预测应激（CUS）诱导大鼠出现抑郁样行为。使用 RNA 测序检测差异表达的 microRNA。通过立体定向注射 AAV 病毒过表达或敲低 miR-204-5p。通过免疫印迹或免疫荧光测定验证氧化标记物和炎症相关蛋白。使用酶联测定试剂盒验证氧化应激酶和产物。通过电子显微镜分析观察突触和超微结构病理学。最后，通过电生理记录分析突触传递。
在这里，我们发现慢性不可预测应激（CUS）后大鼠海马齿状回（DG）区域 miR-204-5p 的表达明显下调，同时这些大鼠 DG 区域发生氧化应激诱导的神经元损伤。相反，在 CUS 大鼠的 DG 区域过表达 miR-204-5p 通过直接靶向 G 蛋白信号调节因子 12（RGS12）减轻氧化应激和神经炎症，同时改善这些 CUS 大鼠的抑郁样行为。此外，下调 miR-204-5p 可诱导 DG 区神经元恶化和大鼠抑郁样行为。
综上所述，这些结果表明 miR-204-5p 在调节 CUS 诱导的抑郁症病理过程中的氧化应激损伤中起关键作用。这些发现为 miR-204-5p 参与与抑郁表型相关的氧化应激机制提供了证据。
Zotero 插件
