Scutellarin alleviates depression-like behaviors induced by LPS in mice partially through inhibition of astrocyte-mediated neuroinflammation

Lu, Liang; Yang, Liu-kun; Yue, Jiao; Wang, Xin‐shang; Qi, Jing-yu; Yang, Fan; Feng, Bo

doi:10.1016/j.neulet.2021.136284

Cited by 14 publications

(4 citation statements)

References 31 publications

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“…However, the changes were consistent with astrocyte activation. Activated astrocytes can promote the secretion of the anti-inflammatory cytokine IL-4 (Lu et al, 2021;Zhang et al, 2021). Hence, the increase in IL-4 after the 2-week CUS intervention may be associated with astrocyte activation.…”

Section: Discussionmentioning

confidence: 99%

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression

Guo

Qiu

Wang

et al. 2022

Front. Cell. Neurosci.

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Major depression is a serious and chronic mental illness. However, its etiology is poorly understood. Although glial cells have been increasingly implicated in the pathogenesis of depression, the specific role of microglia and astrocytes in stress-induced depression remains unclear. Translocator protein (TSPO) has long been considered a marker of neuroinflammation and microglial activation. However, this protein is also present on astrocytes. Thus, it is necessary to explore the relationships between TSPO, microglia, and astrocytes in the context of depression. In this study, C57BL/6J male mice were subjected to chronic unpredictable stress (CUS) for 5 weeks. Subsequently, sucrose preference and tail suspension tests (TSTs) were performed to assess anhedonia and despair in these mice. [18F]DPA-714 positron emission tomography (PET) was adopted to dynamically assess the changes in glial cells before and 2, 4, or 5 weeks after CUS exposure. The numbers of TSPO+ cells, ionized calcium-binding adaptor molecule (Iba)-1+ microglial cells, TSPO+/Iba-1+ cells, glial fibrillary acidic protein (GFAP)+ astrocytes, TSPO+/GFAP+ cells, and TUNEL-stained microglia were quantified using immunofluorescence staining. Real-time PCR was used to evaluate interleukin (IL)-1β, IL-4, and IL-18 expression in the hippocampus. We observed that hippocampal [18F]DPA-714 uptake significantly increased after 2 weeks of CUS. However, the signal significantly decreased after 5 weeks of CUS. CUS significantly reduced the number of Iba-1+, TSPO+, and TSPO+/Iba-1+ cells in the hippocampus, especially in the CA1 and dentate gyrus (DG) subregions. However, this intervention increased the number of GFAP+ astrocytes in the CA2/CA3 subregions of the hippocampus. In addition, microglial apoptosis in the early stage of CUS appeared to be involved in microglia loss. Further, the expression of pro-inflammatory cytokines (IL-1β and IL-18) was significantly decreased after CUS. In contrast, the expression of the anti-inflammatory cytokine IL-4 was significantly increased after 2 weeks of CUS. These results suggested that the CUS-induced dynamic changes in hippocampal [18F]DPA-714 uptake and several cytokines may be due to combined microglial and astrocyte action. These findings provide a theoretical reference for the future clinical applications of TSPO PET.

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Section: Discussionmentioning

confidence: 99%

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression

Guo

Qiu

Wang

et al. 2022

Front. Cell. Neurosci.

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“…The neurons were incubated with glucose-free RPMI 1640 medium and placed in an anaerobic chamber under an atmosphere of 95% N 2 and 5% CO 2 at 37 °C for 3 h. Then, the normal medium was replaced, and the cells were returned to normoxic conditions for reperfusion at 37 °C for 24 h, indicating that the OGD/R model was successfully established [ 18 ]. The breviscapine administration group was pretreated with 50µM breviscapine [ 19 ] before OGD and during reperfusion. Breviscapine were provided by the Kunming Longjin Pharmaceutical Co., Ltd ,Yunnan, China.…”

Section: Methodsmentioning

confidence: 99%

Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods

Wan,

Pei,

Wang

et al. 2023

BMC Med Genomics

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Background Cerebral ischaemia‒reperfusion (I/R) frequently causes late-onset neuronal damage. Breviscapine promotes autophagy in microvascular endothelial cells in I/R and can inhibit oxidative damage and apoptosis. However, the mediation mechanism of breviscapine on neuronal cell death is unclear. Methods First, transcriptome sequencing was performed on three groups of mice: the neuronal normal group (Control group), the oxygen-glucose deprivation/ reoxygenation group (OGD/R group) and the breviscapine administration group (Therapy group). Differentially expressed genes (DEGs) between the OGD/R and control groups and between the Therapy and OGD/R groups were obtained by the limma package. N6-methyladenosine (m6A) methylation-related DEGs were selected by Pearson correlation analysis. Then, prediction and confirmation of drug targets were performed by Swiss Target Prediction and UniProt Knowledgebase (UniProtKB) database, and key genes were obtained by Pearson correlation analysis between m6A-related DEGs and drug target genes. Next, gene set enrichment analysis (GSEA) and Ingenuity pathway analysis (IPA) were used to obtain the pathways of key genes. Finally, a circRNA-miRNA‒mRNA network was constructed based on the mRNAs, circRNAs and miRNAs. Results A total of 2250 DEGs between the OGD/R and control groups and 757 DEGs between the Therapy and OGD/R groups were selected by differential analysis. A total of 7 m6A-related DEGs, including Arl4d, Gm10653, Gm1113, Kcns3, Olfml2a, Stk26 and Tfcp2l1, were obtained by Pearson correlation analysis. Four key genes (Tfcp2l1, Kcns3, Olfml2a and Arl4d) were acquired, and GSEA showed that these key genes significantly participated in DNA repair, e2f targets and the g2m checkpoint. IPA revealed that Tfcp2l1 played a significant role in human embryonic stem cell pluripotency. The circRNA-miRNA‒mRNA network showed that mmu_circ_0001258 regulated Tfcp2l1 by mmu-miR-301b-3p. Conclusions In conclusion, four key genes, Tfcp2l1, Kcns3, Olfml2a and Arl4d, significantly associated with the treatment of OGD/R by breviscapine were identified, which provides a theoretical basis for clinical trials.

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“…In LPS-induced depressed mice, severe body inflammation occurred due to impaired gut barrier as well as the combined effect of endogenous (increased gram-negative bacteria presence) and exogenous (administered intraperitoneally) LPS, activating TLR-4/NF-𝜅B signaling. [23,24] Notably, the expression of TLR-4 in colonic cells significantly increased in the LPS group (p < 0.05), resulting in the phosphorylation and degrada-tion of the NF-𝜅B inhibitor I𝜅B [25] (Figure 3E,F). Consequently, NF-𝜅B P65 inflammatory factor activity surged, prompting the expression of proinflammatory mediators such as TNF-𝛼, IL-1𝛽, and COX-2 [26] (Figure 3G1,G2), collectively contributing to severe gut inflammation.…”

Section: Rk Supplementation Improves Lps-induced Depressed Mice Of Gu...mentioning

confidence: 97%

Raspberry Ketone Prevents LPS‐Induced Depression‐Like Behaviors in Mice by Inhibiting TLR‐4/NF‐κB Signaling Pathway via the Gut‐Brain Axis

Liu,

Dai,

Wang

et al. 2024

Molecular Nutrition Food Res

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ScopeDepression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food‐derived phenolics. Raspberries, renowned globally for their delectable flavor, harbor a phenolic compound known as raspberry ketone (RK). However, the impact of RK on depressive symptoms remains ambiguous. This study aims to investigate the impact of RK on lipopolysaccharide (LPS)‐induced depressed mice and elucidates its potential mechanisms, focusing on the gut‐brain axis.Methods and resultsThrough behavioral tests, RK exerts a notable preventive effect on LPS‐induced depression‐like behaviors in mice. RK proves capable of attenuating gut inflammation, repairing gut barrier impairment, modulating the composition of the gut microbiome (Muribaculaceae, Streptococcus, Lachnospiraceae, and Akkermansia), and promoting the production of short‐chain fatty acids. Furthermore, RK alleviates neuroinflammation by suppressing the TLR‐4/NF‐κB pathway and bolsters synaptic function by elevating levels of neurotrophic factors and synapse‐associated proteins.ConclusionThe current study provides compelling evidence that RK effectively inhibits the TLR‐4/NF‐κB pathway via the gut‐brain axis, leading to the improvement of LPS‐induced depression‐like behaviors in mice. This study addresses the research gap in understanding the antidepressant effects of RK and illuminates the potential of utilizing RK as a functional food for preventing depression.

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Scutellarin alleviates depression-like behaviors induced by LPS in mice partially through inhibition of astrocyte-mediated neuroinflammation

Cited by 14 publications

References 31 publications

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression

Identification of m6A methylation-related genes in cerebral ischaemia‒reperfusion of Breviscapus therapy based on bioinformatics methods

Raspberry Ketone Prevents LPS‐Induced Depression‐Like Behaviors in Mice by Inhibiting TLR‐4/NF‐κB Signaling Pathway via the Gut‐Brain Axis

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