Effects of MFHAS1 on cognitive impairment and dendritic pathology in the hippocampus of septic rats
Effects of MFHAS1 on cognitive impairment and dendritic pathology in the hippocampus of septic rats
复制标题
MFHAS1 对脓毒症大鼠认知障碍和海马树突状病理的影响，
DOI：
10.1016/j.lfs.2019.116822
复制
发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Miao Changhong
中科院分区：
文献类型：
--
作者：
Zhong Jing;Guo Chenyue;Hou Wenting;Shen Na;Miao Changhong
目的 探讨恶性纤维组织细胞瘤扩增序列1（MFHAS1）对认知功能障碍、海马肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β和淀粉样蛋白β肽（Aβ）表达以及海马CA1区树突状病理的影响。 脓毒症相关脑病（SAE）大鼠。主要方法将大鼠随机分为4组：1）对照组（进行假手术），2）对照组+Mfhas1siRNA组（假手术后大鼠脑室内注射Mfhas1siRNA），3）CLP+对照siRNA组（大鼠脑室内注射对照siRNA） 盲肠结扎穿刺（CLP）后），4）CLP加Mfhas1siRNA组（CLP后大鼠脑室内注射Mfhas1siRNA）。通过恐惧条件反射和巴恩斯迷宫测试来检查大鼠的学习和记忆能力。采用酶联免疫吸附法测定TNF-α和IL-1β的浓度。 Western blotting检测siRNA转染效率、MFHAS1和Aβ表达。通过高尔基染色测定 CA1 基底树锥体树突的总分支长度和树突棘密度。主要发现我们观察到，脑室内注射 Mfhas1siRNA 敲低 MFHAS1 可以改善认知障碍，减少 CLP 诱导的海马 TNF-α、IL-1β 和 Aβ 的表达，减轻树突 脊髓锥体神经元损失，以及增加脓毒症大鼠 CA1 基底树的树突状分支。意义 MFHAS1 敲低可以减轻 SAE 大鼠的认知障碍、神经炎症和树突状脊髓损失。
AimsTo investigate the effects of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) on cognitive dysfunction, the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and amyloid β peptide (Aβ) in the hippocampus, as well as dendritic pathology in the hippocampal CA1 region in sepsis-associated encephalopathy (SAE) rats.Main methodsThe rats were randomly divided into four groups: 1) control group (subjected to sham surgery), 2) control plusMfhas1siRNA group (rats received intracerebroventricular injection ofMfhas1siRNA after sham surgery), 3) CLP plus control siRNA group (rats received intracerebroventricular injection of control siRNA after cecal ligation and puncture (CLP)), 4) CLP plusMfhas1siRNA group (rats received intracerebroventricular injection ofMfhas1siRNA after CLP). The learning and memory capabilities of the rats were examined by means of fear conditioning and Barnes maze test. The concentration of TNF-α and IL-1β was determined by enzyme-linked immunosorbent assay. The efficiency of siRNA transfection, MFHAS1 and Aβ expression were detected by Western blotting. Total branch lengths of pyramidal dendrites of the CA1 basilar trees and spine density were determined by Golgi staining.Key findingsWe observed that MFHAS1 knock-down byMfhas1siRNA intracerebroventricular injection could improve cognitive impairment, reduce the expression of TNF-α, IL-1β and Aβ in the hippocampus induced by CLP, and alleviate the dendritic spinal loss of the pyramidal neurons, as well as increase the dendritic branching of the CA1 basilar trees of septic rats.SignificanceMFHAS1 knock-down can alleviate cognitive impairment, neuroinflammation and dendritic spinal loss in SAE rats.