Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
Int J Mol Sci. 2023 Mar 25;24(7):6235. doi: 10.3390/ijms24076235.
Recent evidence indicates that the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, is associated with metabolic disorders such as diabetes and obesity. Various circular RNAs (circRNAs) have been found in brain tissues and recent studies have suggested that circRNAs are related to neuropathological mechanisms in the brain. However, there is a lack of interest in the involvement of circRNAs in metabolic imbalance-related neuropathological problems until now. Herein we profiled and analyzed diverse circRNAs in mouse brain cell lines (Neuro-2A neurons, BV-2 microglia, and C8-D1a astrocytes) exposed to obesity-related in vitro conditions (high glucose, high insulin, and high levels of tumor necrosis factor-alpha, interleukin 6, palmitic acid, linoleic acid, and cholesterol). We observed that various circRNAs were differentially expressed according to cell types with many of these circRNAs conserved in humans. After suppressing the expression of these circRNAs using siRNAs, we observed that these circRNAs regulate genes related to inflammatory responses, formation of synaptic vesicles, synaptic density, and fatty acid oxidation in neurons; scavenger receptors in microglia; and fatty acid signaling, inflammatory signaling cyto that may play important roles in metabolic disorders associated with neurodegenerative diseases.
最近的证据表明，包括阿尔茨海默病在内的神经退行性疾病的发病机制与代谢紊乱有关，如糖尿病和肥胖症。在脑组织中发现了各种环状 RNA（circRNA），最近的研究表明 circRNA 与大脑中的神经病理机制有关。然而，到目前为止，人们对 circRNA 参与与代谢失衡相关的神经病理问题的兴趣不大。在这里，我们对暴露于肥胖相关体外条件（高葡萄糖、高胰岛素和高水平的肿瘤坏死因子-α、白细胞介素 6、棕榈酸、亚油酸和胆固醇）的小鼠脑细胞系（Neuro-2A 神经元、BV-2 小胶质细胞和 C8-D1a 星形胶质细胞）中的多种 circRNA 进行了分析。我们观察到，根据细胞类型，各种 circRNA 表达水平存在差异，其中许多 circRNA 在人类中是保守的。用 siRNA 抑制这些 circRNA 的表达后，我们观察到这些 circRNA 调节与神经元中炎症反应、突触小泡形成、突触密度和脂肪酸氧化相关的基因；小胶质细胞中的清道夫受体；以及脂肪酸信号转导、炎症信号转导细胞因子，这些可能在与神经退行性疾病相关的代谢紊乱中发挥重要作用。
