Esketamine alleviates postoperative cognitive decline via stimulator of interferon genes/ TANK‐binding kinase 1 signaling pathway in aged rats

Li, Yan; Wu, Zhi‐You; Zheng, Wenhua; Wang, Jie-Xia; Yuexin,; Song, Rong‐Xin; Gao, Joseph

doi:10.1016/j.brainresbull.2022.07.004

Cited by 34 publications

(12 citation statements)

References 43 publications

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“…29,31−33 Inhibition of the astrocyte caspase-1 canonical pyroptosis pathway may be a key mechanism underlying the amelioration of POCD in older rats by esketamine. 16 Caspase-1 is also activated in the microglia of elderly mice exposed to isoflurane, regardless of surgery. 9,34 In neonatal rat hippocampal neurons, sevoflurane can trigger the cleavage and activation of caspase-1 substrates, including GSDMD.…”

Section: ■ Discussionmentioning

confidence: 98%

“…The NOD-like receptor protein 3 (NLRP3)/caspase-1 classical pyroptosis pathway is now recognized as a potential culprit of POCD. − Most studies do not distinguish neuronal or glial pyroptosis. ,− Inhibition of the astrocyte caspase-1 canonical pyroptosis pathway may be a key mechanism underlying the amelioration of POCD in older rats by esketamine . Caspase-1 is also activated in the microglia of elderly mice exposed to isoflurane, regardless of surgery. , In neonatal rat hippocampal neurons, sevoflurane can trigger the cleavage and activation of caspase-1 substrates, including GSDMD .…”

Section: Discussionmentioning

confidence: 99%

“…14 Microglia or astrocyte pyroptosis in a caspase-1/GSDMD-dependent manner aggravates POCD. 15,16 Emerging evidence for the abundance of gasdermin E (GSDME) rather than GSDMD in the brain and various neuronal cell lines (e.g., SH-SY5Y neuroblastoma and HT-22 hippocampal neurons) 14,17,18 suggests its potential involvement in the pathogenesis of POCD. Upon activation by caspase-3, the cleaved GSDME-N-terminal fragment forms the transmembrane pore and engages pyroptosis in response to chemotherapeutic drugs and lipopolysaccharide (LPS).…”

Section: ■ Introductionmentioning

confidence: 99%

“…Gasdermin D (GSDMD) downstream of caspase-1 inflammasome activation, the best-characterized pyroptosis pathway, yields an N-terminal domain (N-GSDMD) that triggers pyroptosis in immune cells and gastrointestinal epithelium . Microglia or astrocyte pyroptosis in a caspase-1/GSDMD-dependent manner aggravates POCD. , Emerging evidence for the abundance of gasdermin E (GSDME) rather than GSDMD in the brain and various neuronal cell lines (e.g., SH-SY5Y neuroblastoma and HT-22 hippocampal neurons) ,, suggests its potential involvement in the pathogenesis of POCD. Upon activation by caspase-3, the cleaved GSDME-N-terminal fragment forms the transmembrane pore and engages pyroptosis in response to chemotherapeutic drugs and lipopolysaccharide (LPS). , Several studies have documented that several molecules or drugs attenuate infammasome activation and pyroptosis by facilitating PINK1/Parkin-mediated mitophagy. , However, it remains unclear whether caspase-3/GSDME-dependent pyroptosis exerts detrimental effects on postoperative cognitive capacity.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

Wang

Zhao

Gao

et al. 2023

ACS Chem. Neurosci.

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PTEN-induced kinase 1 (PINK1)-mediated mitophagy and caspase-1/gasdermin D canonical pyroptosis pathways have been implicated in the pathogenesis of postoperative cognitive dysfunction (POCD). However, gasdermin E (GSDME), another recently identified executioner of pyroptosis that can be specifically cleaved by caspase-3, is highly expressed in the brain and neurons. This study aimed to ascertain whether PINK1-dependent mitophagy governs postoperative cognitive capacity through caspase-3/GSDME. Twelve month old male Sprague-Dawley rats underwent exploratory laparotomy under isoflurane anesthesia. Lipopolysaccharide (LPS)-primed SH-SY5Y cells were used to mimic postsurgical neuroinflammation. For the interventional study, rats were administered with adeno-associated virus serotype 9 (AAV9)-mediated silencing of Pink1 and/or caspase-3 inhibitor Ac-DEVD-CHO (Ac-DC). SH-SY5Y cells were treated with siPINK1 and/or Ac-DC. Cognitive performance was assessed using the Morris water maze test. The mitophagy-and pyroptosis-related parameters were determined in the hippocampus and SH-SY5Y cells. Anesthesia/surgery and LPS caused defective PINK1-mediated mitophagy and activation of caspase-3/GSDME-dependent pyroptosis. AAV-9 mediated Pink1 overexpression mitigated cognitive impairment and caspase-3/ GSDME-dependent pyroptosis. Conversely, inhibition of PINK1 aggravates POCD and overactivates neuronal pyroptosis. These abnormalities were rescued by Ac-DC treatment. Collectively, PINK1-mediated mitophagy regulates anesthesia and surgery-induced cognitive impairment by negatively affecting the caspase-3/GSDME pyroptosis pathway, which provides a promising therapeutic target for POCD.

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Section: ■ Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

Wang

Zhao

Gao

et al. 2023

ACS Chem. Neurosci.

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“…In addition, suppressing A1 astrocytes with octreotide cholecystokinin (CCK-8) enhances hippocampus glutamatergic synapse development and postoperative cognitive functions in aged mice [ 28 ] (p. 13). Most unexpectedly, the latest article reports that esketamine administration could alleviate PND post-surgery in aged rats by down-regulating neuronal Aβ-42 and up-regulating hippocampal type A2 astrocytes [ 29 ] (p. 13). Present data suggest that researchers have identified that changes in astrocyte phenotype will have a significant impact on PND.…”

Section: Different Phenotypes Of Reactive Astrocytes and Pndmentioning

confidence: 99%

The Role of Astrocytes in the Mechanism of Perioperative Neurocognitive Disorders

et al. 2022

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Recently, astrocytes are fast climbing the ladder of importance in cognitive-related diseases. Perioperative neurocognitive disorder (PND) is a common consequence of anesthesia and surgery, which is widely investigated in elderly and susceptible individuals. There is no doubt that astrocytes also play an irreplaceable role in the pathogenesis of PND. Reactive astrocytes can be found in the PND model, with an altered phenotype and morphology, suggesting a role in the development of the diseases. As a prominent participant cell in the central inflammatory response, the inflammatory response is unavoidably a crucial pathway in the development of the disease. Astrocytes also play a significant role in the homeostasis of the internal environment, neuronal metabolism, and synaptic homeostasis, all of which have an impact on cognitive function. In this article, we discuss the function of astrocytes in PND in order to establish a framework for investigating treatments for PND that target astrocytes.

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Research progress of postoperative cognitive dysfunction in cardiac surgery under cardiopulmonary bypass

Zhuang

Xu²,

Zheng

et al. 2023

Ibrain

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Cardiopulmonary bypass (CPB) is often used in cardiothoracic surgery because its nonphysiological state causes pathophysiological changes in the body, causing multiorgan and multitissue damage to varying degrees. Postoperative cognitive dysfunction (POCD) is a common central nervous system complication after cardiac surgery. The etiology and mechanism of POCD are not clear. Neuroinflammation, brain mitochondrial dysfunction, cerebral embolism, ischemia, hypoxia, and other factors are related to the pathogenesis of POCD. There is a close relationship between CPB and POCD, as CPB can cause inflammation, hypoxia and reperfusion injury, and microemboli formation, all of which can trigger POCD. POCD increases medical costs, seriously affects patients' quality of life, and increases mortality. Currently, there is a lack of effective treatment methods for POCD. Commonly used methods include preoperative health management, reducing inflammation response during surgery, preventing microemboli formation, and implementing individualized rehabilitation programs after surgery. Strengthening preventive measures can minimize the occurrence of POCD and its adverse effects.

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Esketamine alleviates postoperative cognitive decline via stimulator of interferon genes/ TANK‐binding kinase 1 signaling pathway in aged rats

Cited by 34 publications

References 43 publications

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

The Role of Astrocytes in the Mechanism of Perioperative Neurocognitive Disorders

Research progress of postoperative cognitive dysfunction in cardiac surgery under cardiopulmonary bypass

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