Senkyunolide I Protects against Sepsis‐Associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

Xie, Jian; Zhao, Zhenzhen; Zhu, Chenglong; Guo, Yu; Wang, Jun; Deng, Xiaoming; Wang, Jiafeng

doi:10.1155/2021/6647258

Cited by 22 publications

(15 citation statements)

References 33 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mice were housed in SD devices under an LD cycle as previously described. 51 , 53 , 54 After two weeks of acclimatization, the mice were divided into four groups including the non-SD group, the SD group, a forced-recovery-in-normal-sleep-condition (SD-FR-NSC) mouse model for four weeks after the four weeks of SD, and a normal-sleep-condition (SD-NSC) mouse model for four weeks after the four weeks of SD. For the SD group, the sweep bar worked every 1.5 minutes during the light cycle (ZT0–12) for four weeks.…”

Section: Methodsmentioning

confidence: 99%

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Huang

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose Sleep loss markedly affects the structure and function of the lacrimal gland and may cause ocular surface disease as a common public health problem. This study aims to investigate the circadian disturbance caused by sleep loss leading to dysfunction of extraorbital lacrimal glands (ELGs). Methods A mouse sleep deprivation (SD) model for sleep loss studies was built in C57BL/6J male mice. After four weeks, the ELGs were collected at three-hour intervals during a 24-hour period. The Jonckheere-Terpstra-Kendall algorithm was used to determine the composition, phase, and rhythmicity of transcriptomic profiles in ELGs. Furthermore, we compared the non-sleep-deprived and SD-treated mouse ELG (i) reactive oxygen species (ROS) by fluorescein staining, (ii) DNA damage by immunostaining for γ-H2Ax, and (iii) circadian migration of immune cells by immunostaining for CD4, CD8, γδ-TCR, CD64, and CX3CR1. Finally, we also evaluated (i) the locomotor activity and core body temperature rhythm of mice and (ii) the mass, cell size, and tear secretion of the ELGs. Results SD dramatically altered the composition and phase-associated functional enrichment of the circadian transcriptome, immune cell trafficking, metabolism, cell differentiation, and neural secretory activities of mouse ELGs. Additionally, SD caused the ROS accumulation and consequent DNA damage in the ELGs, and the ELG dysfunction caused by SD was irreversible. Conclusions SD damages the structure, function, and diurnal oscillations of ELGs. These results highlight comprehensive characterization of insufficient sleep–affected ELG circadian transcriptome that may provide a new therapeutic approach to counteract the effects of SD on ELG function.

show abstract

Section: Methodsmentioning

confidence: 99%

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Huang

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…On the other hand, it has been reported that the progression of SAE could lead to the secretion of pro-inflammatory cytokines [27, 32]. In addition, IL-1β, IL-6, and TNF-α levels were upregulated during the development of SAE [32]. Thus, these 3 cytokines were selected for analysis in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Another research also demonstrated that Emodin attenuated LPS-induced apoptosis and inflammation in ATDC5 cells [13]. On the other hand, it has been reported that the progression of SAE could lead to the secretion of pro-inflammatory cytokines [27, 32]. In addition, IL-1β, IL-6, and TNF-α levels were upregulated during the development of SAE [32].…”

Section: Discussionmentioning

confidence: 99%

Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

Gao

Wang

et al. 2021

Pathobiology

View full text Add to dashboard Cite

Objective: Sepsis-associated encephalopathy (SAE) is a severe and common complication of sepsis and can induce cognitive dysfunction and apoptosis of neurons and neuroinflammation. Emodin has been confirmed to have anti-inflammatory effects. Thus, we sought to investigate the role of Emodin in SAE. Methods: The cecal ligation and puncture (CLP) method was used for the establishment of SAE in mice model. For treatment of Emodin, intraperitoneal injection of 20 mg/kg Emodin was performed before the surgery. The Morris water maze and open field tests were carried for measurement of cognitive dysfunction. Hematoxylin and eosin staining was for histological analysis of hippocampus. Cell apoptosis of hippocampus neurons was measured by TUNEL staining. Pro-inflammatory and anti-inflammatory cytokines in hippocampus tissue homogenate were evaluated by ELISA. BDNF/TrkB signaling-related proteins (TrkB, p-TrkB, and BDNF), autophagy-related proteins (LC3 II/I and Beclin-1), and apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were detected by Western blotting. Results: Emodin significantly inhibited apoptosis and induced autophagy in hippocampal neurons of CLP-treated mice. In addition, Emodin significantly ameliorated CLP-induced cognitive dysfunction and pathological injury in mice. Meanwhile, Emodin notably inhibited CLP-induced inflammatory responses in mice via upregulation of BDNF/TrkB signaling, while the effect of Emodin was partially reversed in the presence of K252a (BDNF/TrkB signaling inhibitor). Conclusion: Emodin significantly inhibited the progression of SAE via mediation of BDNF/TrkB signaling. Thus, Emodin might serve as a new agent for SAE treatment.

show abstract

“…The FCT was performed following the protocol as previously described [54,55]. On the day of training, mice were placed into an enclosed training chamber and allowed to explore for 180 s. Mice were then exposed to a tone (30 s, 70 dB, 3 kHz), followed by a 2 s foot shock (0.45 mA).…”

Section: Behavioral Testsmentioning

confidence: 99%

SIRT3 Protects Against Cognitive Dysfunction Induced by Sepsis-associated Encephalopathy Via JNK/p66Shc-Regulated Mitochondrial Apoptosis in Mice

Lyu

Luo

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Sepsis-associated encephalopathy (SAE) is one of the severe central nervous system complications. Oxidative stress and synaptic dysfunction were involved in cognitive impairment induced by SAE. The mitochondrial nicotinamide adenine dinucleotide (NAD+) dependent deacetylase, sirtuin3 (SIRT3), plays a critical role in regulating mitochondrial function. The aim of this study was to evaluate the effect of SIRT3 in cognitive dysfunction induced by SAE.Methods: Mice were treated with lipopolysaccharide (LPS, 10 mg/kg, i.p.). Contextual and cue memory were evaluated by fear conditioning test in wild-type (WT) and SIRT3-deficient (SIRT3-/-) mice. Synapse-associated proteins and mitochondrial apoptosis-associated protein were examined by western blotting. In vitro studies, acetylation levels of cyclophilin D (CypD) were detected with different SIRT3 deacetylase activity in HT22 cells after LPS-induced microglia supernatant (Mi-sup) exposure. Oxidative stress was detected by reactive oxygen species (ROS) staining, and mitochondrial membrane potential (MMP) was detected by JC-1 staining, and mitochondrial membrane permeability transition pore (MPTP) opening was detected by Calcein and Co2+ staining. Furthermore, the phosphorylation levels of mitochondrial p66Shc and JNK were evaluated by western blotting.Results: SIRT3 expression was diminished in hippocampus of mice after LPS treatment. SIRT3-deficiency contributed to more severe contextual memory loss and synaptic dysfunction, decreased ratio of Bcl-2/Bax and increased Cyt C release to cytoplasm in hippocampus compared with wild-type controls. In HT22 cells, lysine acetylation levels of CypD were significantly increased after Mi-sup exposure and further enhanced with 3-TYP (SIRT3 deacetylation inhibitor) pretreatment, in association with the accumulation of ROS, declined MMP and increased MPTP opening, as well as the increased mitochondrial Cyt C release and phosphorylation levels of mitochondrial JNK and p66Shc-Ser36. SIRT3 overexpression restored CypD lysine acetylation levels and MPTP opening in HT22 cells after Mi-sup exposure and reduced mitochondrial JNK and p66Shc activation. Conclusions: Taken together, our results showed that SIRT3-mediated CypD deacetylation was involved in LPS-induced hippocampal synaptic dysfunction, via ROS accumulation, declined MMP, increased MPTP opening, mitochondrial Cyt C release and mitochondrial apoptosis of hippocampal neuron via JNK/p66Shc pathway. Our results revealed that SIRT3 may be a promising therapeutic and diagnostic target for cognitive dysfunction induced by SAE.

show abstract

Senkyunolide I Protects against Sepsis‐Associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

Cited by 22 publications

References 33 publications

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

SIRT3 Protects Against Cognitive Dysfunction Induced by Sepsis-associated Encephalopathy Via JNK/p66Shc-Regulated Mitochondrial Apoptosis in Mice

Contact Info

Product

Resources

About