Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Otolaryngology, Zhongshan Hospital, Fudan University, Shanghai, China.
Life Sci. 2019 Oct 15;235:116822. doi: 10.1016/j.lfs.2019.116822. Epub 2019 Aug 30.
To 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.
The rats were randomly divided into four groups: 1) control group (subjected to sham surgery), 2) control plus Mfhas1 siRNA group (rats received intracerebroventricular injection of Mfhas1 siRNA after sham surgery), 3) CLP plus control siRNA group (rats received intracerebroventricular injection of control siRNA after cecal ligation and puncture (CLP)), 4) CLP plus Mfhas1 siRNA group (rats received intracerebroventricular injection of Mfhas1 siRNA 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.
We observed that MFHAS1 knock-down by Mfhas1 siRNA 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.
MFHAS1 knock-down can alleviate cognitive impairment, neuroinflammation and dendritic spinal loss in SAE rats.
研究恶性纤维组织细胞瘤扩增序列 1（MFHAS1）对脓毒症相关性脑病（SAE）大鼠认知功能障碍、海马肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β和淀粉样β肽（Aβ）表达以及海马 CA1 区树突病理的影响。
将大鼠随机分为四组：1）对照组（接受假手术），2）对照组加 Mfhas1 siRNA 组（假手术后大鼠接受脑室注射 Mfhas1 siRNA），3）CLP 加对照组 siRNA 组（CLP 后大鼠接受脑室注射对照组 siRNA），4）CLP 加 Mfhas1 siRNA 组（CLP 后大鼠接受脑室注射 Mfhas1 siRNA）。通过恐惧条件反射和 Barnes 迷宫试验检测大鼠的学习记忆能力。酶联免疫吸附试验检测 TNF-α和 IL-1β浓度。Western blot 检测 siRNA 转染效率、MFHAS1 和 Aβ表达。高尔基染色检测 CA1 基底树总分支长度和棘突密度。
我们观察到脑室注射 Mfhas1 siRNA 敲低 MFHAS1 可以改善 CLP 诱导的认知障碍，降低海马 TNF-α、IL-1β和 Aβ的表达，减轻脓毒症大鼠锥体神经元的树突棘丢失，并增加 CA1 基底树的树突分支。
敲低 MFHAS1 可减轻 SAE 大鼠的认知障碍、神经炎症和树突棘丢失。
