Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice
Neuroinflammation plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1...
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doaj-13ab18388863428da57d2f7b26726fb02020-11-24T23:07:59ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532018-07-011210.3389/fnbeh.2018.00138375882Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged MiceShangchun Duan0Xueqin Wang1Gong Chen2Chengxuan Quan3Shuangquan Qu4Jianbin Tong5Jianbin Tong6Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, ChinaCenter for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anesthesiology, Hunan Children’s Hospital, Changsha, ChinaDepartment of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, ChinaCenter for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, ChinaNeuroinflammation plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1 by necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in D-Galactose (D-Gal)-induced aged mice. The mice were subjected to anesthesia and partial hepatectomy, and necrostatin-1 was administered intraperitoneally 1 h prior to anesthesia and surgery. Cognitive function and movement were tested 24 h after surgery by open field, Barnes maze and puzzle box. The hippocampal tissues were collected to detect the following: neuroinflammation (Iba-1, IL-1α, IL-1β, TNF-α), Necroptosis (Propidium Iodide (PI) labeling, RIPK1, nuclear transcription factor kappa B (NF-κB) and neuroplasticity (doublecortin (DCX), NR2B, GluA1, GluA2). We found that anesthesia and surgery induced a significant deficit in spatial memory acquisition and impairment of executive function and memory to simple task in D-Galactose-induced aged mice. Inhibiting RIPK1 by necrostatin-1 strikingly mitigated cognitive impairment and alleviated postoperative amplified neuroinflammation, necroptosis and GluA1 loss in hippocampus. These suggest that targeting RIPK1 by necrostatin-1 may serve as a promising therapeutics for prevention of POCD in elderly patients.https://www.frontiersin.org/article/10.3389/fnbeh.2018.00138/fullsurgerycognitive deficitneuroinflammationnecrostatin-1elderly |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shangchun Duan Xueqin Wang Gong Chen Chengxuan Quan Shuangquan Qu Jianbin Tong Jianbin Tong |
spellingShingle |
Shangchun Duan Xueqin Wang Gong Chen Chengxuan Quan Shuangquan Qu Jianbin Tong Jianbin Tong Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice Frontiers in Behavioral Neuroscience surgery cognitive deficit neuroinflammation necrostatin-1 elderly |
author_facet |
Shangchun Duan Xueqin Wang Gong Chen Chengxuan Quan Shuangquan Qu Jianbin Tong Jianbin Tong |
author_sort |
Shangchun Duan |
title |
Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice |
title_short |
Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice |
title_full |
Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice |
title_fullStr |
Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice |
title_full_unstemmed |
Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice |
title_sort |
inhibiting ripk1 limits neuroinflammation and alleviates postoperative cognitive impairments in d-galactose-induced aged mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Behavioral Neuroscience |
issn |
1662-5153 |
publishDate |
2018-07-01 |
description |
Neuroinflammation plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1 by necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in D-Galactose (D-Gal)-induced aged mice. The mice were subjected to anesthesia and partial hepatectomy, and necrostatin-1 was administered intraperitoneally 1 h prior to anesthesia and surgery. Cognitive function and movement were tested 24 h after surgery by open field, Barnes maze and puzzle box. The hippocampal tissues were collected to detect the following: neuroinflammation (Iba-1, IL-1α, IL-1β, TNF-α), Necroptosis (Propidium Iodide (PI) labeling, RIPK1, nuclear transcription factor kappa B (NF-κB) and neuroplasticity (doublecortin (DCX), NR2B, GluA1, GluA2). We found that anesthesia and surgery induced a significant deficit in spatial memory acquisition and impairment of executive function and memory to simple task in D-Galactose-induced aged mice. Inhibiting RIPK1 by necrostatin-1 strikingly mitigated cognitive impairment and alleviated postoperative amplified neuroinflammation, necroptosis and GluA1 loss in hippocampus. These suggest that targeting RIPK1 by necrostatin-1 may serve as a promising therapeutics for prevention of POCD in elderly patients. |
topic |
surgery cognitive deficit neuroinflammation necrostatin-1 elderly |
url |
https://www.frontiersin.org/article/10.3389/fnbeh.2018.00138/full |
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