Role of lipocalin-2 in surgery-induced cognitive decline in mice: a signal from neuron to microglia

Xiang, Xuwu; Tang, Xiaodong; Yu, Yang; Xie, Shulan; Liu, Lu; Chen, ManLi; Zhang, Rong; Kang, Xianhui; Zheng, Yan‐Song; Yang, Guang; Gan, Shuyuan; Zhu, Shengmei

doi:10.1186/s12974-022-02455-5

Cited by 14 publications

(12 citation statements)

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“…Inhibition of NF‐κB can reduce the expression of pro‐inflammatory cytokines (such as IL‐6, IL‐1β, and TNF‐α) and increase the expression of BDNF, thereby ameliorating the cognitive decline of diabetic mice 51 . The involvement of Lcn2 in apoptosis extends to insulin resistance, cancer, and nervous system diseases 52,53 . However, further investigation is required to determine its potential role in particle‐induced conditions.…”

Section: Discussionmentioning

confidence: 99%

“… 51 The involvement of Lcn2 in apoptosis extends to insulin resistance, cancer, and nervous system diseases. 52 , 53 However, further investigation is required to determine its potential role in particle‐induced conditions. Our findings that CS exposure augmented astrocytic Lcn2 and neurotoxicity in the hippocampus are in agreement with the bulk of the research.…”

Section: Discussionmentioning

confidence: 99%

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Nicotine suppresses crystalline silica‐induced astrocyte activation and neuronal death by inhibiting NF‐κB in the mouse hippocampus

Cao,

Li,

et al. 2023

CNS Neurosci Ther

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AimsExposure to crystalline silica (CS) in occupational settings induces chronic inflammation in the respiratory system and, potentially, the brain. Some workers are frequently concurrently exposed to both CS and nicotine. Here, we explored the impact of nicotine on CS‐induced neuroinflammation in the mouse hippocampus.MethodsIn this study, we established double‐exposed models of CS and nicotine in C57BL/6 mice. To assess depression‐like behavior, experiments were conducted at 3, 6, and 9 weeks. Serum inflammatory factors were analyzed by ELISA. Hippocampus was collected for RNA sequencing analysis and examining the gene expression patterns linked to inflammation and cell death. Microglia and astrocyte activation and hippocampal neuronal death were assessed using immunohistochemistry and immunofluorescence staining. Western blotting was used to analyze the NF‐κB expression level.ResultsMice exposed to CS for 3 weeks showed signs of depression. This was accompanied by elevated IL‐6 in blood, destruction of the blood–brain barrier, and activation of astrocytes caused by an increased NF‐κB expression in the CA1 area of the hippocampus. The elevated levels of astrocyte‐derived Lcn2 and upregulated genes related to inflammation led to higher neuronal mortality. Moreover, nicotine mitigated the NF‐κB expression, astrocyte activation, and neuronal death, thereby ameliorating the associated symptoms.ConclusionSilica exposure induces neuroinflammation and neuronal death in the mouse hippocampal CA1 region and depressive behavior. However, nicotine inhibits CS‐induced neuroinflammation and neuronal apoptosis, alleviating depressive‐like behaviors in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nicotine suppresses crystalline silica‐induced astrocyte activation and neuronal death by inhibiting NF‐κB in the mouse hippocampus

Cao,

Li,

et al. 2023

CNS Neurosci Ther

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“…Excess in ammatory factor production in the aged brain following peripheral trauma is dependent on the activation of microglia [44][45][46]. Microglia, which are important immune cells in the CNS, are regarded as tissue macrophages in the brain [47].…”

Section: Discussionmentioning

confidence: 99%

Adiponectin attenuates splenectomy-induced cognitive deficits by alleviating neuroinflammation and oxidative stress via the TLR4/MyD88/NF-κb signaling pathway in aged rats

Zhang

Guo

Yang

et al. 2022

Preprint

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Background Perioperative neurocognitive disorder (PND) is a common adverse event after surgical trauma in elderly patients. The pathogenesis of PND is still unclear. Adiponectin (APN) is a plasma protein secreted by adipose tissue. We have reported that decreased APN expression is associated with PND patients. APN may be a promising therapeutic agent for PND. However, the neuroprotective mechanism of APN in PND is still unclear. Methods Eighteen month-old male Sprague Dawley rats were assigned to six groups: the sham, sham + APN (intragastric (i.g.) administration of 10 µg/kg/day for 20 days before splenectomy), PND (splenectomy), PND + APN, PND + TAK-242 (intraperitoneal (i.p.) administration of 3 mg/kg TAK-242) and PND + APN + LPS (i.p. administration of 2 mg/kg LPS). The cognitive function of the rats was assessed with the Morris water maze (MWM) test. Immunohistochemistry/ immunofluorescence, western blotting and ELISA were used to evaluate the activation of the TLR4/NF-κb axis, oxidative stress-mediated apoptosis, microglial activation and proinflammatory cytokine expression in the hippocampus. Results We first found that APN treatment significantly improved learning and cognitive function in the MWM test after surgical trauma. Further experiments showed that APN could inhibit the TLR4/MyD88/NF-κb p65 pathway to decrease the degree of oxidative damage (MDA, SOD and caspase 3) and microglia-mediated neuroinflammation (IBA1, TNF-α, IL-1β and IL-6). The TLR4 antagonist TAK-242 had a similar effect as APN, while the TLR4 agonist LPS abolished the beneficial effect of APN. Conclusions APN exerts a neuroprotective effect against cognitive deficits induced by peripheral trauma, and the possible mechanisms include inhibition of oxidative stress and neuroinflammation, which is mediated by suppression of the TLR4/MyD88/NF-κb signaling pathway. We propose that APN is a promising candidate for PND treatment.

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“…Perioperative neurocognitive disorders (PND), including POD and postoperative cognitive dysfunction (POCD), are common following anesthesia and surgery in older patients and signi cantly increase morbidity and mortality [16,17]. Neuroin ammation in the hippocampus, including microglial in ammatory response and neuronal apoptosis, plays an essential role in cognitive dysfunction [18,19]. Initial evidence has shown that rats transfused with old RBCs or receiving free-Hb and mice receiving intracerebral heme injection suffer from neuroin ammation and neurological de cits [9,20].…”

Section: Introductionmentioning

confidence: 99%

Free-heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4/MyD88/NF-kB signaling pathway

Wei,

Zhang,

Cheng

et al. 2023

Preprint

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Background: Red blood cells (RBCs) transfusion is related to perioperative neurocognitive disorders. The toxic effect of free-heme has been identified in many pathologies. However, the underlying mechanisms of RBCs transfusion or free-heme in cognitive impairment have not been clearly explored. Therefore, this research was conducted to determine the mechanism of heme-induced neuroinflammation and cognitive impairment. Methods: Rats were received intraperitoneal injection of hemin alone or combined with intracerebroventricular injection of Hemopexin (HPX), and MWM test was conducted to measure cognitive function. The elimination condition of heme-HPX complexes was evaluated by flow cytometry for CD91+ cells. The microglial inflammatory response in rat brain and BV2 cells was observed by immunofluorescence staining of Iba-1 and ELISA analysis of TNF-α, IL-1β and IL-6. Furthermore, neuronal apoptosis in HT22 cells alone and in HT22 + BV2 coculture system was detected by flow cytometry and immunofluorescence staining. Finally, western blot was conducted to detect TLR4/MyD88/NF-kB proteins in rat brain and BV2 cells treated with hemin or combined with pathway inhibitors. Additionally, the M1 surface marker CD86 was observed in BV2 cells to further confirm neuroinflammation. Results: Intraperitoneal injection of hemin induced cognitive impairment, increase of CD91+ cells, up-regulation of TNF-α and IL-1β, down-regulation of IL-6, activation of microglia, and activation of the TLR4/MyD88/NF-kB signaling pathway in rat brain. Significantly, intracerebroventricular injection of HPX reduced the above effects. Hemin induced boost of TNF-α, IL-1β and IL-6 in BV2 cells, as well as apoptosis in HT22 cells. Notably, when HT22 cells were cocultured with BV2 cells, apoptosis was significantly increased. Hemin also induced activation of the TLR4/MyD88/NF-kB signaling pathway and increased the M1 surface marker CD86 in BV2 cells, and inhibiting this pathway reduced the inflammatory responses. Conclusions: Free-heme induces cognitive impairment, and the underlying mechanism may involve neuronal apoptosis and microglial inflammation via the TLR4/MyD88/NF-kB signaling pathway. HPX may have potential therapeutic effects.

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Role of lipocalin-2 in surgery-induced cognitive decline in mice: a signal from neuron to microglia

Cited by 14 publications

References 58 publications

Nicotine suppresses crystalline silica‐induced astrocyte activation and neuronal death by inhibiting NF‐κB in the mouse hippocampus

Nicotine suppresses crystalline silica‐induced astrocyte activation and neuronal death by inhibiting NF‐κB in the mouse hippocampus

Adiponectin attenuates splenectomy-induced cognitive deficits by alleviating neuroinflammation and oxidative stress via the TLR4/MyD88/NF-κb signaling pathway in aged rats

Free-heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4/MyD88/NF-kB signaling pathway

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