title: Regulation of Sirtuin 3-Mediated Deacetylation of Cyclophilin D Attenuated Cognitive Dysfunction Induced by Sepsis-Associated Encephalopathy in Mice.
abstract: The present study aimed to investigate cognitive dysfunction in the hippocampus induced by sepsis-associated encephalopathy (SAE) via acetylation of cyclophilin D (CypD) and opening of mitochondrial permeability transition pore. It also explored whether activating sirtuin 3 (SIRT3) can mediate deacetylation of CypD and prevent the development of SAE. Male mice were randomly assigned to six groups: sham group, cecal ligation puncture group, CypD siRNA transfection (CypD-si) group, CypD control siRNA transfection (CypD-c) group, SIRT3 overexpression vector pcDNA3.1 (SIRT3-p) group, and SIRT3 empty vector pcDNA3.1 (SIRT3-v) group (n = 18). The CypD-si and CypD-c groups were transfected with CypD siRNA and CypD control siRNA, respectively. The SIRT3-p and SIRT3-v groups were injected with SIRT3 pcDNA3.1 and vector pcDNA3.1, respectively. The learning and memory function was assessed using the learning version of the Morris water maze test. Then, cell apoptosis and the levels of CypD, acetylated CypD, SIRT-3, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-3 in the hippocampus were determined. The levels of CypD and acetylation of CypD increased in the hippocampus induced by SAE. Increasing SIRT3 and decreasing CypD can attenuate cognitive impairment and neuroapoptosis, and protect the integrity of mitochondrial membrane from damage and restore the protein expressions of IL-6, TNF-α, and caspase-3. Activating SIRT3-mediated deacetylation of CypD attenuated learning and memory dysfunction induced by SAE.
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Si
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China. hongguang_bao@hotmail.com.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Bao
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: XiaoXiao
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Lingqing
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jing
mesh_terms: D000107:Acetylation; D000818:Animals; D060825:Cognitive Dysfunction / Q000150:complications / Q000378:metabolism*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D065166:Sepsis-Associated Encephalopathy / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D056566:Sirtuin 3 / Q000502:physiology*
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; C000631446:PPIF protein, mouse; C525046:Sirt3 protein, mouse; D056566:Sirtuin 3; D021983:Cyclophilins
keywords: Cognitive dysfunction; Cyclophilin D; Deacetylation; Mitochondrial permeability transition pore; Sepsis-associated encephalopathy; Sirtuin 3