Resveratrol Mitigates Hippocampal Tau Acetylation and Cognitive Deficit by Activation SIRT1 in Aged Rats following Anesthesia and Surgery

Yan, Jing; Luo, Ailin; Sun, Renhua; Tang, Xiaole; Zhao, Yilin; Zhang, Jie; Zhou, Bing; Zheng, Hua; Yu, Honghui; Li, Shiyong

doi:10.1155/2020/4635163

Cited by 32 publications

(18 citation statements)

References 68 publications

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“…We observed a decreased SIRT1 expression in the hippocampus 1 and 3 days after anesthesia and surgery. Our results are in keeping with recent works [39,40]. SIRT1 is enriched in the nuclei and cytoplasm of microglia, implicating microglia as the target of SIRT1 in hippocampus.…”

Section: Discussionsupporting

confidence: 93%

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

Sun¹,

Wang²,

Ye³

et al. 2021

Preprint

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BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current studies mainly focus on microglia activation, however, less is known about the mechanism underlying neuronal synaptic changes involved in microglia activation. Recent studies indicate that silent information regulator 1 (SIRT1) plays critical roles in different neurological disorders, and is involved in microglia activation. Herein, we evaluated the effects of SIRT1 activation on POCD.MethodsExploratory laparotomy were employed on mice (12-14 month) under sevoflurane anesthesia to establish model of POCD. Transcriptional changes in hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression were verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, as well as dystrophic neurites and dendritic spine density were determined. Cognitive functions were evaluated by Y maze and Morris water maze.ResultsSIRT1 expression levels were downregulated in anesthesia and surgery group. Anesthesia and surgery lead to microglia morphology alteration, enhanced synaptic engulfment, dendritic spine loss, and cognitive deficits in our mice model, all of which were alleviated by SRT1720 administration.ConclusionOur study unveils one of the roles of SIRT1 in POCD pathogenesis. SIRT1 activation may represent a therapeutic strategy for prevention and treatment of POCD.

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Section: Discussionsupporting

confidence: 93%

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

Sun¹,

Wang²,

Ye³

et al. 2021

Preprint

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“… 140 Our study and other studies found that the reduction of SIRT1 was associated with postoperative cognitive impairment by activating the neuroinflammatory pathway and inhibiting neurotrophic factors. 141 , 142 Considering our previous findings that SIRT1 mediated abnormal tau modification in an aged POCD model, 143 it is plausible that SIRT1 is involved in sleep disturbance-related POCD. Future studies are needed to validate this hypothesis.…”

Section: Potential Mechanisms Underlying Perioperative Sleep Disturbance-associated Pocdmentioning

confidence: 98%

The Role of Perioperative Sleep Disturbance in Postoperative Neurocognitive Disorders

Wang¹,

Duan²,

Tang³

et al. 2021

NSS

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Postoperative neurocognitive disorder (PND) increases the length of hospital stay, mortality, and risk of long-term cognitive impairment. Perioperative sleep disturbance is prevalent and commonly ignored and may increase the risk of PND. However, the role of perioperative sleep disturbances in PND remains unclear. Nocturnal sleep plays an indispensable role in learning, memory, and maintenance of cerebral microenvironmental homeostasis. Hospitalized sleep disturbances also increase the incidence of postoperative delirium and cognitive dysfunction. This review summarizes the role of perioperative sleep disturbances in PND and elucidates the potential mechanisms underlying sleep-deprivation-mediated PND. Activated neuroinflammation and oxidative stress; impaired function of the blood-brain barrier and glymphatic pathway; decreased hippocampal brain-derived neurotrophic factor, adult neurogenesis, and sirtuin1 expression; and accumulated amyloid-beta proteins are associated with PND in individuals with perioperative sleep disorders. These findings suggest that the improvement of perioperative sleep might reduce the incidence of postoperative delirium and postoperative cognitive dysfunction. Future studies should further investigate the role of perioperative sleep disturbance in PND.

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“…Postoperative cognitive dysfunction (POCD) is one of the most common postoperative complications in elderly patients ( Granger and Barnett, 2021 ) and is characterized by declines in learning, memory, attention, and executive capability following anesthesia and surgery ( Chen et al, 2019 ; Yan et al, 2020 ). Clinical evidence indicates that POCD may contribute to increased mortality, decreased quality of life, prolonged hospitalization, and increased burden on the medical care system ( Steinmetz et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

Wang

Zhou

et al. 2021

Front. Mol. Neurosci.

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Postoperative cognitive dysfunction (POCD) is a common postoperative neurocognitive complication in elderly patients. However, the specific pathogenesis is unknown, and it has been demonstrated that neuroinflammation plays a key role in POCD. Recently, increasing evidence has proven that the locus coeruleus noradrenergic (LCNE) system participates in regulating neuroinflammation in some neurodegenerative disorders. We hypothesize that LCNE plays an important role in the neuroinflammation of POCD. In this study, 400 μg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected intracerebroventricularly into each rat 7 days before anesthesia/surgery to deplete the locus coeruleus (LC) noradrenaline (NE). We applied a simple laparotomy and brief upper mesenteric artery clamping surgery as the rat POCD model. The open field test, novel objection and novel location (NL) recognition, and Morris water maze (MWM) were performed to assess postoperative cognition. High-performance liquid chromatography (HPLC) was used to measure the level of NE in plasma and brain tissues, and immunofluorescence staining was applied to evaluate the activation of microglia and astrocytes. We also used enzyme-linked immune-sorbent assay (ELISA) to assess the levels of inflammatory cytokines and brain-derived neurotrophic factor (BDNF). Pretreatment with DSP-4 decreased the levels of systemic and central NE, increased the level of interleukin-6 (IL-6) in the plasma at 6 h after the surgery, decreased the concentration of IL-6 in the prefrontal cortex and hippocampus, and decreased the level of interleukin-1β (IL-1β) in the plasma, prefrontal cortex, and hippocampus at 1 week postoperatively. In addition, DSP-4 treatment attenuated hippocampal-dependent learning and memory impairment in rats with POCD, with a downregulation of the activation of microglia and astrocytes in the prefrontal cortex and hippocampus. In conclusion, these findings provide evidence of the effects of LCNE in modulating neuroinflammation in rats with POCD and provide a new perspective in the prevention and treatment of POCD.

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Resveratrol Mitigates Hippocampal Tau Acetylation and Cognitive Deficit by Activation SIRT1 in Aged Rats following Anesthesia and Surgery

Cited by 32 publications

References 68 publications

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

The Role of Perioperative Sleep Disturbance in Postoperative Neurocognitive Disorders

A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

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