当前位置: X-MOL 学术J. Neuroinflammation › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Knockdown of long non-coding RNA SOX2OT downregulates SOX2 to improve hippocampal neurogenesis and cognitive function in a mouse model of sepsis-associated encephalopathy
Journal of Neuroinflammation ( IF 9.3 ) Pub Date : 2020-10-25 , DOI: 10.1186/s12974-020-01970-7
Jialin Yin 1 , Yanan Shen 1 , Yanna Si 1 , Yuan Zhang 1 , Jiayue Du 1 , Xiajuan Hu 1 , Mengmeng Cai 1 , Hongguang Bao 1 , Yan Xing 2
Affiliation  

Aberrant hippocampal neurogenesis is an important pathological feature of sepsis-associated encephalopathy. In the current study, we examined the potential role of the long noncoding RNA (lncRNA) sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2OT), a known regulator of adult neurogenesis in sepsis-induced deficits in hippocampal neurogenesis and cognitive function. Sepsis was induced in adult C57BL/6 J male mice by cecal ligation and perforation (CLP) surgery. Randomly selected CLP mice were transfected with short interfering RNAs (siRNAs) against SOX2OT or SOX2, or with scrambled control siRNA. Cognitive behavior was tested 8–12 days post-surgery using a Morris water maze. Western blotting and RT-qPCR were used to determine expression of SOX2, Ki67, doublecortin (DCX), nestin, brain lipid-binding protein, and glial fibrillary acidic protein (GFAP) in the hippocampus. The number of bromodeoxyuridine (BrdU)+/DCX+ cells, BrdU+/neuronal nuclei (NeuN)+ neurons, and BrdU+/GFAP+ glial cells in the dentate gyrus were assessed by immunofluorescence. CLP mice showed progressive increases in SOX2OT and SOX2 mRNA levels on days 3, 7, and 14 after CLP surgery, accompanied by impaired cognitive function. Sepsis led to decrease in all neuronal markers in the hippocampus, except GFAP. Immunofluorescence confirmed the decreased numbers of BrdU+/DCX+ cells and BrdU+/NeuN+ neurons, and increased numbers of BrdU+/GFAP+ cells. SOX2OT knockdown partially inhibited the effects of CLP on levels of SOX2 and neuronal markers, neuronal populations in the hippocampus, and cognitive function. SOX2 deficiency recapitulated the effects of SOX2OT knockdown. SOX2OT knockdown improves sepsis-induced deficits in hippocampal neurogenesis and cognitive function by downregulating SOX2 in mice. Inhibiting SOX2OT/SOX2 signaling may be effective for treating or preventing neurodegeneration in sepsis-associated encephalopathy.

中文翻译:

敲除长链非编码 RNA SOX2OT 下调 SOX2 以改善败血症相关脑病小鼠模型的海马神经发生和认知功能

海马神经发生异常是败血症相关脑病的重要病理特征。在目前的研究中,我们检查了长链非编码 RNA (lncRNA) 性别决定区 Y-box 2 (SOX2) 重叠转录物 (SOX2OT) 的潜在作用,SOX2OT 是败血症诱导的海马神经发生缺陷中成人神经发生的已知调节剂和认知功能。通过盲肠结扎和穿孔 (CLP) 手术在成年 C57BL/6 J 雄性小鼠中诱导败血症。随机选择的 CLP 小鼠用针对 SOX2OT 或 SOX2 的短干扰 RNA (siRNA) 或乱序对照 siRNA 转染。使用莫里斯水迷宫在手术后 8-12 天测试认知行为。使用蛋白质印迹和 RT-qPCR 测定 SOX2、Ki67、双皮质素 (DCX)、巢蛋白、脑脂质结合蛋白、和海马中的胶质纤维酸性蛋白(GFAP)。通过免疫荧光评估齿状回中溴脱氧尿苷 (BrdU)+/DCX+ 细胞、BrdU+/神经元核 (NeuN)+ 神经元和 BrdU+/GFAP+ 神经胶质细胞的数量。CLP 小鼠在 CLP 手术后第 3、7 和 14 天显示 SOX2OT 和 SOX2 mRNA 水平逐渐增加,并伴有认知功能受损。脓毒症导致海马中所有神经元标记物的减少,但 GFAP 除外。免疫荧光证实 BrdU+/DCX+ 细胞和 BrdU+/NeuN+ 神经元数量减少,而 BrdU+/GFAP+ 细胞数量增加。SOX2OT 敲低部分抑制了 CLP 对 SOX2 和神经元标记物水平、海马神经元群和认知功能的影响。SOX2 缺乏概括了 SOX2OT 敲低的影响。SOX2OT 敲低通过下调小鼠的 SOX2 来改善败血症引起的海马神经发生和认知功能缺陷。抑制 SOX2OT/SOX2 信号可能有效治疗或预防脓毒症相关脑病的神经变性。
更新日期:2020-10-26
down
wechat
bug