SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction

BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) p...
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Autor*in:	Yi Sun [verfasserIn] Yuzhu Wang [verfasserIn] Fan Ye [verfasserIn] Victoria Cui [verfasserIn] Dandan Lin [verfasserIn] Hui Shi [verfasserIn] Yan Zhang [verfasserIn] Anshi Wu [verfasserIn] Changwei Wei [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	SIRT1 microglial activation synaptic engulfment neuroinflammation postoperative cognitive dysfunction

Übergeordnetes Werk:	In: Frontiers in Aging Neuroscience - Frontiers Media S.A., 2010, 14(2022)
Übergeordnetes Werk:	volume:14 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fnagi.2022.943842

Katalog-ID:	DOAJ086515950

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520			\|a BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
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allfields	10.3389/fnagi.2022.943842 doi (DE-627)DOAJ086515950 (DE-599)DOAJ97ca9999f69b4807b783c665615716cd DE-627 ger DE-627 rakwb eng RC321-571 Yi Sun verfasserin aut SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD. SIRT1 microglial activation synaptic engulfment neuroinflammation postoperative cognitive dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry Yuzhu Wang verfasserin aut Fan Ye verfasserin aut Victoria Cui verfasserin aut Dandan Lin verfasserin aut Hui Shi verfasserin aut Yan Zhang verfasserin aut Anshi Wu verfasserin aut Changwei Wei verfasserin aut In Frontiers in Aging Neuroscience Frontiers Media S.A., 2010 14(2022) (DE-627)629834350 (DE-600)2558898-9 16634365 nnns volume:14 year:2022 https://doi.org/10.3389/fnagi.2022.943842 kostenfrei https://doaj.org/article/97ca9999f69b4807b783c665615716cd kostenfrei https://www.frontiersin.org/articles/10.3389/fnagi.2022.943842/full kostenfrei https://doaj.org/toc/1663-4365 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022
spelling	10.3389/fnagi.2022.943842 doi (DE-627)DOAJ086515950 (DE-599)DOAJ97ca9999f69b4807b783c665615716cd DE-627 ger DE-627 rakwb eng RC321-571 Yi Sun verfasserin aut SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD. SIRT1 microglial activation synaptic engulfment neuroinflammation postoperative cognitive dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry Yuzhu Wang verfasserin aut Fan Ye verfasserin aut Victoria Cui verfasserin aut Dandan Lin verfasserin aut Hui Shi verfasserin aut Yan Zhang verfasserin aut Anshi Wu verfasserin aut Changwei Wei verfasserin aut In Frontiers in Aging Neuroscience Frontiers Media S.A., 2010 14(2022) (DE-627)629834350 (DE-600)2558898-9 16634365 nnns volume:14 year:2022 https://doi.org/10.3389/fnagi.2022.943842 kostenfrei https://doaj.org/article/97ca9999f69b4807b783c665615716cd kostenfrei https://www.frontiersin.org/articles/10.3389/fnagi.2022.943842/full kostenfrei https://doaj.org/toc/1663-4365 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022
allfields_unstemmed	10.3389/fnagi.2022.943842 doi (DE-627)DOAJ086515950 (DE-599)DOAJ97ca9999f69b4807b783c665615716cd DE-627 ger DE-627 rakwb eng RC321-571 Yi Sun verfasserin aut SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD. SIRT1 microglial activation synaptic engulfment neuroinflammation postoperative cognitive dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry Yuzhu Wang verfasserin aut Fan Ye verfasserin aut Victoria Cui verfasserin aut Dandan Lin verfasserin aut Hui Shi verfasserin aut Yan Zhang verfasserin aut Anshi Wu verfasserin aut Changwei Wei verfasserin aut In Frontiers in Aging Neuroscience Frontiers Media S.A., 2010 14(2022) (DE-627)629834350 (DE-600)2558898-9 16634365 nnns volume:14 year:2022 https://doi.org/10.3389/fnagi.2022.943842 kostenfrei https://doaj.org/article/97ca9999f69b4807b783c665615716cd kostenfrei https://www.frontiersin.org/articles/10.3389/fnagi.2022.943842/full kostenfrei https://doaj.org/toc/1663-4365 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022
allfieldsGer	10.3389/fnagi.2022.943842 doi (DE-627)DOAJ086515950 (DE-599)DOAJ97ca9999f69b4807b783c665615716cd DE-627 ger DE-627 rakwb eng RC321-571 Yi Sun verfasserin aut SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD. SIRT1 microglial activation synaptic engulfment neuroinflammation postoperative cognitive dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry Yuzhu Wang verfasserin aut Fan Ye verfasserin aut Victoria Cui verfasserin aut Dandan Lin verfasserin aut Hui Shi verfasserin aut Yan Zhang verfasserin aut Anshi Wu verfasserin aut Changwei Wei verfasserin aut In Frontiers in Aging Neuroscience Frontiers Media S.A., 2010 14(2022) (DE-627)629834350 (DE-600)2558898-9 16634365 nnns volume:14 year:2022 https://doi.org/10.3389/fnagi.2022.943842 kostenfrei https://doaj.org/article/97ca9999f69b4807b783c665615716cd kostenfrei https://www.frontiersin.org/articles/10.3389/fnagi.2022.943842/full kostenfrei https://doaj.org/toc/1663-4365 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022
allfieldsSound	10.3389/fnagi.2022.943842 doi (DE-627)DOAJ086515950 (DE-599)DOAJ97ca9999f69b4807b783c665615716cd DE-627 ger DE-627 rakwb eng RC321-571 Yi Sun verfasserin aut SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD. SIRT1 microglial activation synaptic engulfment neuroinflammation postoperative cognitive dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry Yuzhu Wang verfasserin aut Fan Ye verfasserin aut Victoria Cui verfasserin aut Dandan Lin verfasserin aut Hui Shi verfasserin aut Yan Zhang verfasserin aut Anshi Wu verfasserin aut Changwei Wei verfasserin aut In Frontiers in Aging Neuroscience Frontiers Media S.A., 2010 14(2022) (DE-627)629834350 (DE-600)2558898-9 16634365 nnns volume:14 year:2022 https://doi.org/10.3389/fnagi.2022.943842 kostenfrei https://doaj.org/article/97ca9999f69b4807b783c665615716cd kostenfrei https://www.frontiersin.org/articles/10.3389/fnagi.2022.943842/full kostenfrei https://doaj.org/toc/1663-4365 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022
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Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. 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callnumber-first	R - Medicine
author	Yi Sun
spellingShingle	Yi Sun misc RC321-571 misc SIRT1 misc microglial activation misc synaptic engulfment misc neuroinflammation misc postoperative cognitive dysfunction misc Neurosciences. Biological psychiatry. Neuropsychiatry SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction
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topic_title	RC321-571 SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction SIRT1 microglial activation synaptic engulfment neuroinflammation postoperative cognitive dysfunction
topic	misc RC321-571 misc SIRT1 misc microglial activation misc synaptic engulfment misc neuroinflammation misc postoperative cognitive dysfunction misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_unstemmed	misc RC321-571 misc SIRT1 misc microglial activation misc synaptic engulfment misc neuroinflammation misc postoperative cognitive dysfunction misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_browse	misc RC321-571 misc SIRT1 misc microglial activation misc synaptic engulfment misc neuroinflammation misc postoperative cognitive dysfunction misc Neurosciences. Biological psychiatry. Neuropsychiatry
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title	SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction
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title_full	SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction
author_sort	Yi Sun
journal	Frontiers in Aging Neuroscience
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author_browse	Yi Sun Yuzhu Wang Fan Ye Victoria Cui Dandan Lin Hui Shi Yan Zhang Anshi Wu Changwei Wei
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doi_str_mv	10.3389/fnagi.2022.943842
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title_sort	sirt1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction
callnumber	RC321-571
title_auth	SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction
abstract	BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
abstractGer	BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
abstract_unstemmed	BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
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title_short	SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction
url	https://doi.org/10.3389/fnagi.2022.943842 https://doaj.org/article/97ca9999f69b4807b783c665615716cd https://www.frontiersin.org/articles/10.3389/fnagi.2022.943842/full https://doaj.org/toc/1663-4365
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author2	Yuzhu Wang Fan Ye Victoria Cui Dandan Lin Hui Shi Yan Zhang Anshi Wu Changwei Wei
author2Str	Yuzhu Wang Fan Ye Victoria Cui Dandan Lin Hui Shi Yan Zhang Anshi Wu Changwei Wei
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doi_str	10.3389/fnagi.2022.943842
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up_date	2024-07-03T21:09:06.461Z
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Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. 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SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction

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