NLRC3 Delays the Progression of AD in APP/PS1 Mice via Inhibiting PI3K Activation

Zha, Lihuang; Yu, Zaixin; Fang, Jian; Zhou, Li; Zhou, Jun

doi:10.1155/2020/5328031

Cited by 20 publications

(12 citation statements)

References 39 publications

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“…Dietary supplemented baicalin zinc reduced DON-induced expression of p-Nrf2 and HO-1 in the piglets intestine (Zha et al 2020a ). Similar effect was observed for the complex of baicalin copper in another study (Zha et al 2020b ). Grape seed proanthocyanidin extract increased the expression of Nrf2 and its downstream genes decreased in the response to oxidative stress triggered by ZEA in murine liver and Sertoli cells (Long et al 2016 , 2017 ) as well as AFB1 induced oxidative stress and inflammation in broilers (Rajput et al 2019 ).…”

Section: Natural Antioxidantssupporting

confidence: 88%

Nrf2: a main responsive element in cells to mycotoxin-induced toxicity

Kozieł

Kowalska

Piastowska-Ciesielska

2021

Arch Toxicol

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Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor participating in response to cellular oxidative stress to maintain the redox balance. Generation of reactive oxygen species (ROS) and, in consequence, oxidative stress, are physiological as well as pathological processes which take place in almost all types of cells. Nrf2, in response to oxidative stress, activates expression and production of antioxidant enzymes to remove free radicals. However, the role of Nrf2 seems to be more sophisticated and its increased expression observed in cancer cells allows to draw a conclusion that its role is tissue—and condition—dependent. Interestingly, Nrf2 might also play a crucial role in response to environmental factors like mycotoxins. Thus, the aim of the study is to review the role of Nrf2 in cells exposed to most common mycotoxins to check if the Nrf2 signaling pathway serves as the main response element to mycotoxin-induced oxidative stress in human and animal cells and if it can be a target of detoxifying agents.

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Section: Natural Antioxidantssupporting

confidence: 88%

Nrf2: a main responsive element in cells to mycotoxin-induced toxicity

Kozieł

Kowalska

Piastowska-Ciesielska

2021

Arch Toxicol

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“…Mounting evidence indicated that in ammation may affect mitochondrial function, membrane polarity and oxidative phosphorylation, which may further lead to oxidative stress and apoptosis [11,[52][53][54]. Microglia and astrocytes are main mediators of in ammation in the brain [55]. In our study reported here, the EDA administration signi cantly decreased microglial activation and attenuated astrocyte dysfunction.…”

Section: Discussionsupporting

confidence: 58%

Edaravone Ameliorates Depressive and Anxiety-like Behaviors via Sirt1/Nrf2/HO-1/Gpx4 Pathway

Dang

Wang

et al. 2021

Preprint

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Background: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms.Methods: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. C57BL/6J mice were intraperitoneally injected with EDA or Vehicle daily for 10 days. Behaviors tests were then carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, measurement of MDA, SOD, GSH and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi(GPX4)-EGFP infusion.Results: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. Additionally, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage and energy metabolism in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors.Conclusion: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

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“…Mounting evidence indicated that inflammation may affect mitochondrial function, membrane polarity and oxidative phosphorylation, which may further lead to OS and apoptosis [ 11 , 65 – 67 ]. Microglia and astrocytes are main mediators of inflammation in the brain [ 68 ]. In our study reported here, the EDA administration significantly decreased microglial activation and attenuated astrocyte dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway

Dang

Wang

et al. 2022

J Neuroinflammation

195

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Background The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. Methods A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)–EGFP infusion. Results The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. Conclusion These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

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NLRC3 Delays the Progression of AD in APP/PS1 Mice via Inhibiting PI3K Activation

Cited by 20 publications

References 39 publications

Nrf2: a main responsive element in cells to mycotoxin-induced toxicity

Nrf2: a main responsive element in cells to mycotoxin-induced toxicity

Edaravone Ameliorates Depressive and Anxiety-like Behaviors via Sirt1/Nrf2/HO-1/Gpx4 Pathway

Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway

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