Silencing IFNγ inhibits A1 astrocytes and attenuates neurogenesis decline and cognitive impairment in endotoxemia

Lü, Yanyan; Yang, Yanliang; Peng, Zhouyangfan; Xie, Liling; Zhong, Xiaoli; Fang, Liang; Yuan, Chuang; Lü, Ben

doi:10.1016/j.bbrc.2020.10.084

Cited by 16 publications

(6 citation statements)

References 21 publications

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“…Previous investigations have demonstrated that berberine and its correlative derivate exhibited extensive anti-inflammation and anti-tumor roles, which could be a new potential therapeutic drug ( Kumar et al, 2015 ; Prajwala et al, 2020 ). Herein, our study revealed that the utilization of berberine before sepsis could avoid the progress of cognition function disorder in CLP-caused septic mice ( Lu et al, 2020 ). More studies unveiled that such protection effect for cognition damage was closely associated with the decrease of pro-inflammation cell factors and the mitigation A1 astrocyte ( Sun et al, 2019 ; Liu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 93%

“…And just as importantly, activated microglia can release a number of inflammatory mediators, the most important of which in SAE are TNF-α, IL-1α, and C1qA. These inflammatory mediators will further facilitate the formation of neuron-toxic A1 astrocytes and aggravate neuroinflammation ( Xu et al, 2019 ; Lu et al, 2020 ). Then sustained damage of endothelial cells caused neuroinflammation leads to cerebral perfusion disorder, which makes SAE a sophisticated and intractable problem.…”

Section: Discussionmentioning

confidence: 99%

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Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy

Shi

Cavagnaro

et al. 2021

Front. Pharmacol.

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As a life-threatening multiple organ dysfunction attributable to maladjusted host immune responses to infection, sepsis is usually the common pathway to serious prognosis and death for numerous infectious diseases all over the world. Sepsis-associated encephalopathy (SAE) is frequently complicated by septic conditions, and is one of the most important reasons for increased mortality and poor outcomes in septic patients which is still an urgent clinical problem need to be solved. In this research, a conspicuously discovery of treatment-related translational use for berberine was elaborated. The results revealed that berberine treatment significantly restored cognitive impairment in sepsis mice. Reduced expression levels of TNF-α, IL-1α, and C1qA were exhibited in the hippocampus of the berberine treatment group, and attenuated effect of declining neo-neuron, activation of microglia and astrocytes in the hippocampus of mice with sepsis were also found. Moreover, berberine inhibits microglia-stressed A1 astrocytes by inhibiting HMGB1 signaling was revealed, then the molecular mechanism of HMGB1/RAGE signaling inhibition leads to the better outcome of SAE was elucidated. To summarize, this research indicated that berberine targets HMGB1/RAGE signaling to inhibit microglia-stressed A1 astrocyte and neo-neuron decline, which consequently alleviates sepsis-induced cognitive impairment. Collectively, berberine may serve as potential therapeutic drug and HMGB1/RAGE signaling would be a novel target for medicine development for treating SAE.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy

Shi

Cavagnaro

et al. 2021

Front. Pharmacol.

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“…Hippocampal neurogenesis is largely regulated by environmental in uences, and functionally implicated in behavioral responses to sepsis in adult animals [12,38]. Sepsis-induced neuroin ammation is considered to be a major trigger for hippocampal neurogenesis de cits [39]. A recent study shows that LPS triggers in ammatory cytokines production of astrocytes cultured in vitro, and conditioned medium from LPS-incubated astrocytes can reduce NSCs proliferation and enhance its differentiation into astrocytes [40].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates neuroinflammation-mediated hippocampal neurogenesis impairment in sepsis-associated encephalopathy mice through central α2A-adrenoceptor

Guo,

Zhang,

Dai

et al. 2023

Preprint

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Sepsis-associated encephalopathy (SAE), one of the common complications of sepsis, is associated with higher ICU mortality, prolonged hospitalization and long-term cognitive decline. Sepsis can induce neuroinflammation, which negatively affects hippocampal neurogenesis. Dexmedetomidine has been shown to protect against SAE. However, the potential mechanism remains unclear. In this study, we added lipopolysaccharide (LPS)-stimulated astrocytes-conditioned media (LPS-CM) to neural stem cells (NSCs) culture, which were pretreated with dexmedetomidine in the presence or absence of the α2-adrenoceptor antagonist yohimbine or the α2A-adrenoceptor antagonist BRL-44408. LPS-CM impaired the neurogenesis of NSCs, characterized by decreased proliferation, enhanced gliogenesis and declined viability. Dexmedetomidine alleviated LPS-CM-induced impairments of neurogenesis in a dose-dependent manner. Yohimbine, as well as BRL-44408, reversed the effects of dexmedetomidine. We established a mouse model of SAE by cecal ligation and perforation (CLP). CLP induced astrocyte-related neuroinflammation and hippocampal neurogenesis deficits, companied with learning and memory decline, which was reversed by dexmedetomidine. The effect of dexmedetomidine was blocked by BRL-44408. Collectively, our findings support the conclusion that dexmedetomidine can protect against SAE, likely mediated by the combination of inhibiting neuroinflammation via astrocytic α2A-adrenoceptor with attenuating neuroinflammation-induced hippocampal neurogenesis deficits via NSCs α2A-adrenoceptor.

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“…In addition, IFN-γ promotes cognitive impairment in endotoxemia by enhancing microglia-induced A1 astrocytes. Targeting IFN-γ is a novel strategy for preventing or treating cognitive dysfunction in patients with SAE [52]. The activation of the NLRP3 inflammasome in microglia induces the conversion of A1 astrocytes, thereby exacerbating a decline in neo-neurons and leading to cognitive impairment following exposure to LPS [53].…”

Section: Crosstalk Between Microglia Neurons and Astrocytesmentioning

confidence: 99%

Microglial Activation: Key Players in Sepsis-Associated Encephalopathy

Hu,

Xie,

Zhang

et al. 2023

Brain Sciences

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Sepsis-associated encephalopathy (SAE) is a common brain dysfunction, which results in severe cognitive and neurological sequelae and an increased mortality rate in patients with sepsis. Depending on the stimulus, microglia (resident macrophages in the brain that are involved in SAE pathology and physiology) can adopt two polarization states (M1/M2), corresponding to altered microglial morphology, gene expression, and function. We systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE and demonstrated that microglia are closely related to SAE occurrence and development, and concomitant cognitive impairment. Finally, some potential therapeutic approaches that can prime microglia and neuroinflammation toward the beneficial restorative microglial phenotype in SAE were outlined.

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Silencing IFNγ inhibits A1 astrocytes and attenuates neurogenesis decline and cognitive impairment in endotoxemia

Cited by 16 publications

References 21 publications

Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy

Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy

Dexmedetomidine attenuates neuroinflammation-mediated hippocampal neurogenesis impairment in sepsis-associated encephalopathy mice through central α2A-adrenoceptor

Microglial Activation: Key Players in Sepsis-Associated Encephalopathy

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