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Effects of MFHAS1 on Cognitive Impairment and Dendritic Pathology in the Hippocampus of Septic Rats

Jing Zhong  ¹ , Chenyue Guo  ¹ , Wenting Hou  ¹ , Na Shen  ² , Changhong Miao  ³

• ¹ Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
• ² Department of Otolaryngology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: shen.na@zs-hospital.sh.cn.
• ³ Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: ziteng1934@aliyun.com.

Abstract

Aims: 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.

Main methods: 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.

Key findings: 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.

Significance: MFHAS1 knock-down can alleviate cognitive impairment, neuroinflammation and dendritic spinal loss in SAE rats.

Keywords: Dendritic spine density; IL-1β; MFHAS1; Sepsis-associated encephalopathy.