Qian-Juan Fang1,2, Bing-Huan Chi1,2, Qi-Cheng Lin1,2, Chen-Miao Huang1,2, Shao-Wu Jin1,2, Jia-Jing Cai1,2, Ke Nan1,2, Yuan Han1,2, Yuan-Xiang Tao3, Hong Cao1,2, Jun Li1,2. 1. Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027, Zhejiang, China. 2. Zhejiang Province Key Lab of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027, Zhejiang, China. 3. Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey Newark, NJ 07103, New Jersey, USA.
Abstract
OBJECTIVES: Elderly patients often suffer from cognitive dysfunction following surgery. However, the mechanisms underlying this phenomenon still remain unclear. This study investigated the critical part of Sirtuin-1 (SIRT1)-mediated autophagy and apoptosis in surgery-induced cognitive impairment. METHODS: The aged (16-month-old) male C57BL/6 mice underwent anesthesia and surgery. Some mice received intraperitoneal injections of resveratrol, which is an activator of SIRT1, prior to exposure to splenectomy. To examine learning and memory behavior in different sets, the study performed a Morris water maze. Tissues from the hippocampus were harvested 1, 3 and 7 days after surgery. Western blotting and immunofluorescence analysis determined the expression of autophagy- and apoptosis- associated protein. RESULTS: This article demonstrated surgery but not anesthesia considerably affected memory behavior and downregulated SIRT1 expression in the aged mice. Interestingly, rescue of hippocampal SIRT1 expression ameliorated the cognitive impairment in the elderly mice under splenectomy. In addition, surgical trauma decreased Beclin-1 protein levels and the LC3-II/LC3-I ratio, while expression of p62, Bax and cleaved caspase-3 in hippocampal neurons increased. However, rescue of hippocampal SIRT1 expression considerably attenuated the surgery-induced downregulation of Beclin-1, increased the ratio of LC3-II/LC3-I, and decreased expression of p62, Bax, and cleaved caspase-3. CONCLUSION: These findings suggest that surgery-induced downregulation of hippocampal SIRT1 participates in cognitive impairment after surgery by inhibiting the autophagy process and activating apoptosis. AJTR
OBJECTIVES: Elderly patients often suffer from cognitive dysfunction following surgery. However, the mechanisms underlying this phenomenon still remain unclear. This study investigated the critical part of Sirtuin-1 (SIRT1)-mediated autophagy and apoptosis in surgery-induced cognitive impairment. METHODS: The aged (16-month-old) male C57BL/6 mice underwent anesthesia and surgery. Some mice received intraperitoneal injections of resveratrol, which is an activator of SIRT1, prior to exposure to splenectomy. To examine learning and memory behavior in different sets, the study performed a Morris water maze. Tissues from the hippocampus were harvested 1, 3 and 7 days after surgery. Western blotting and immunofluorescence analysis determined the expression of autophagy- and apoptosis- associated protein. RESULTS: This article demonstrated surgery but not anesthesia considerably affected memory behavior and downregulated SIRT1 expression in the aged mice. Interestingly, rescue of hippocampal SIRT1 expression ameliorated the cognitive impairment in the elderly mice under splenectomy. In addition, surgical trauma decreased Beclin-1 protein levels and the LC3-II/LC3-I ratio, while expression of p62, Bax and cleaved caspase-3 in hippocampal neurons increased. However, rescue of hippocampal SIRT1 expression considerably attenuated the surgery-induced downregulation of Beclin-1, increased the ratio of LC3-II/LC3-I, and decreased expression of p62, Bax, and cleaved caspase-3. CONCLUSION: These findings suggest that surgery-induced downregulation of hippocampal SIRT1 participates in cognitive impairment after surgery by inhibiting the autophagy process and activating apoptosis. AJTR
Authors: Qun Wang; Jianfeng Xu; George E Rottinghaus; Agnes Simonyi; Dennis Lubahn; Grace Y Sun; Albert Y Sun Journal: Brain Res Date: 2002-12-27 Impact factor: 3.252
Authors: J T Moller; P Cluitmans; L S Rasmussen; P Houx; H Rasmussen; J Canet; P Rabbitt; J Jolles; K Larsen; C D Hanning; O Langeron; T Johnson; P M Lauven; P A Kristensen; A Biedler; H van Beem; O Fraidakis; J H Silverstein; J E Beneken; J S Gravenstein Journal: Lancet Date: 1998-03-21 Impact factor: 79.321
Authors: In Hye Lee; Liu Cao; Raul Mostoslavsky; David B Lombard; Jie Liu; Nicholas E Bruns; Maria Tsokos; Frederick W Alt; Toren Finkel Journal: Proc Natl Acad Sci U S A Date: 2008-02-22 Impact factor: 11.205