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Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a common complication in the elderly. Histone deacetylases (HDACs) are a class of enzymes that control the acetylation status of intracellular proteins. Thus, we explored whether HDACs trigger the release of high mobility group box 1 (HMGB1...

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Autores principales: Huang, Chen-miao, Cai, Jia-jing, Jin, Shao-wu, Lin, Qi-cheng, Fang, Qian-juan, Nan, Ke, Han, Yuan, Ge, Wen-wei, Liu, Yu, Tao, Yuan-xiang, Cao, Hong, Li, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180279/
https://www.ncbi.nlm.nih.gov/pubmed/34103963
http://dx.doi.org/10.2147/JIR.S304060
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author Huang, Chen-miao
Cai, Jia-jing
Jin, Shao-wu
Lin, Qi-cheng
Fang, Qian-juan
Nan, Ke
Han, Yuan
Ge, Wen-wei
Liu, Yu
Tao, Yuan-xiang
Cao, Hong
Li, Jun
author_facet Huang, Chen-miao
Cai, Jia-jing
Jin, Shao-wu
Lin, Qi-cheng
Fang, Qian-juan
Nan, Ke
Han, Yuan
Ge, Wen-wei
Liu, Yu
Tao, Yuan-xiang
Cao, Hong
Li, Jun
author_sort Huang, Chen-miao
collection PubMed
description OBJECTIVE: Perioperative neurocognitive disorders (PND) are a common complication in the elderly. Histone deacetylases (HDACs) are a class of enzymes that control the acetylation status of intracellular proteins. Thus, we explored whether HDACs trigger the release of high mobility group box 1 (HMGB1) through altering the acetylation status in the hippocampi of aged mice. MATERIALS AND METHODS: The effect of the Class IIa HDAC in PND was explored using an in vivo form of splenectomy. Sixteen-month-old healthy male C57BL/6J mice were randomly divided into five groups: control, anesthesia plus sham surgery, anesthesia plus splenectomy, LMK235 treatment, and PBS treatment. The hippocampi were harvested on either first, third, or seventh postoperative day. Cognitive function was assessed via a Morris water maze (MWM) test. Quantitative RT-PCR, Western blots and ELISAs were carried out to assess the targeted gene expression at transcriptional and translational levels. RESULTS: Splenectomy led to a significant deficiency in spatial memory acquisition, marked decreases in mRNA and protein levels of HDAC4 and HDAC5 in the hippocampus, and increases in the levels of total HMGB1 and acetylated HMGB1. In a similar fashion to splenectomy, treatment with the HDAC4/5 inhibitor LMK235 produced impaired spatial memory and an increase in the expression of HMGB1 and its acetylated counterpart in the hippocampus. CONCLUSION: These results suggest that surgery leads to PND through class IIa HDAC downregulation-triggered HMGB1 release in hippocampus of aged mice. HDACs may be a potential therapeutic target for postoperative cognitive dysfunction.
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spelling pubmed-81802792021-06-07 Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice Huang, Chen-miao Cai, Jia-jing Jin, Shao-wu Lin, Qi-cheng Fang, Qian-juan Nan, Ke Han, Yuan Ge, Wen-wei Liu, Yu Tao, Yuan-xiang Cao, Hong Li, Jun J Inflamm Res Original Research OBJECTIVE: Perioperative neurocognitive disorders (PND) are a common complication in the elderly. Histone deacetylases (HDACs) are a class of enzymes that control the acetylation status of intracellular proteins. Thus, we explored whether HDACs trigger the release of high mobility group box 1 (HMGB1) through altering the acetylation status in the hippocampi of aged mice. MATERIALS AND METHODS: The effect of the Class IIa HDAC in PND was explored using an in vivo form of splenectomy. Sixteen-month-old healthy male C57BL/6J mice were randomly divided into five groups: control, anesthesia plus sham surgery, anesthesia plus splenectomy, LMK235 treatment, and PBS treatment. The hippocampi were harvested on either first, third, or seventh postoperative day. Cognitive function was assessed via a Morris water maze (MWM) test. Quantitative RT-PCR, Western blots and ELISAs were carried out to assess the targeted gene expression at transcriptional and translational levels. RESULTS: Splenectomy led to a significant deficiency in spatial memory acquisition, marked decreases in mRNA and protein levels of HDAC4 and HDAC5 in the hippocampus, and increases in the levels of total HMGB1 and acetylated HMGB1. In a similar fashion to splenectomy, treatment with the HDAC4/5 inhibitor LMK235 produced impaired spatial memory and an increase in the expression of HMGB1 and its acetylated counterpart in the hippocampus. CONCLUSION: These results suggest that surgery leads to PND through class IIa HDAC downregulation-triggered HMGB1 release in hippocampus of aged mice. HDACs may be a potential therapeutic target for postoperative cognitive dysfunction. Dove 2021-05-31 /pmc/articles/PMC8180279/ /pubmed/34103963 http://dx.doi.org/10.2147/JIR.S304060 Text en © 2021 Huang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Huang, Chen-miao
Cai, Jia-jing
Jin, Shao-wu
Lin, Qi-cheng
Fang, Qian-juan
Nan, Ke
Han, Yuan
Ge, Wen-wei
Liu, Yu
Tao, Yuan-xiang
Cao, Hong
Li, Jun
Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice
title Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice
title_full Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice
title_fullStr Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice
title_full_unstemmed Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice
title_short Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice
title_sort class iia hdac downregulation contributes to surgery-induced cognitive impairment through hmgb1-mediated inflammatory response in the hippocampi of aged mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180279/
https://www.ncbi.nlm.nih.gov/pubmed/34103963
http://dx.doi.org/10.2147/JIR.S304060
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