The role of damage associated molecular pattern molecules (DAMPs) and permeability of the blood-brain barrier in depression and neuroinflammation

Serna-Rodríguez, María Fernanda; Bernal-Vega, Sofía; Barquera, José Alfonso Ontiveros-Sánchez de la; Camacho‐Morales, Alberto; Pérez-Maya, Antonio Alí

doi:10.1016/j.jneuroim.2022.577951

Cited by 41 publications

(26 citation statements)

References 116 publications

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“…However, in depression, astrocyte activation may play an important role in promoting inflammation, and the relationship between astrocyte activation and inflammation is bidirectional. The BBB stands as a unique architectural marvel within the brain, composed of intricate capillary vessels lined by vascular endothelial cells, pericytes, basement membrane constituents, and essential glial cells such as astrocytes and microglia 54 . Stimulation by stress hormones or cytokines, as part of the inflammatory process, can lead to the opening of tight junction and adherent junction proteins in the BBB 39,55,56 .…”

Section: Discussionmentioning

confidence: 99%

Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment‐resistant depression following electroconvulsive therapy

Xu,

Xie,

Yao

et al. 2023

Psychiatry Clin Neurosci

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AimThis study aimed to investigate the neuroinflammatory hypothesis of depression and the potential anti‐inflammatory effect of electroconvulsive therapy (ECT) in vivo, utilizing astrocyte‐derived extracellular vesicles (ADEVs) isolated from plasma.MethodsA total of 40 patients with treatment‐resistant depression (TRD) and 35 matched healthy controls (HCs) were recruited at baseline, and 34 TRD patients completed the post‐ECT visits. Blood samples were collected at baseline and post‐ECT. Plasma ADEVs were isolated and confirmed, and the concentrations of two astrocyte markers (glial fibrillary acidic protein (GFAP) and S100β), an EV marker cluster of differentiation (CD) 81, and nine inflammatory markers in ADEVs were measured as main analyses. Additionally, correlation analysis was conducted between clinical features and ADEV protein levels as exploratory analysis.ResultsAt baseline, the TRD group exhibited significantly higher levels of two astrocyte markers GFAP and S100β, as well as CD81 compared to the HCs. Inflammatory markers interferon (IFN)‐γ, interleukin (IL)‐1β, IL‐4, IL‐6, tumor necrosis factor (TNF)‐α, IL‐10, and IL‐17A were also significantly higher in the TRD group. After ECTs, there was a significant reduction in the levels of GFAP, S100β, and CD81, along with a significant decrease in the levels of IFN‐γ and IL‐4. Furthermore, higher levels of GFAP, S100β, CD81 and inflammatory cytokines were associated with more severe depressive symptoms and poorer cognitive function.ConclusionThis study provides direct insight supporting the astrocyte activation and neuroinflammatory hypothesis of depression using ADEVs. ECT may exert anti‐inflammatory effect through inhibition of such activation of astrocytes.This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 99%

Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment‐resistant depression following electroconvulsive therapy

Xu,

Xie,

Yao

et al. 2023

Psychiatry Clin Neurosci

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“…29,30 Also, IL-2, −5, −7, −12, interferon-γ (IFN-γ), granulocyte colony-stimulating factor (G-CSF), granulocyte monocyte colony-stimulating factor (GM-CSF), regulated on activation, normal T cell expressed and secreted (RANTES), interferon gamma-induced protein 10 (IP-10) are recognized as pleiotropic regulators of inflammation. [31][32][33][34][35][36] Major antiinflammatory cytokines encompass IL-1 receptor antagonist (IL-1ra), IL-4, −9, −10, −11, and IL-13. 30,37 Studies that can "visualize" the body's response to the formation of an aneurysm in the brain may help understand the mechanisms responsible for their formation as well as in the search for non-invasive targets for aneurysm pharmacotherapy.…”

Section: Introductionmentioning

confidence: 99%

Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients

Kamińska¹,

Maciejczyk²,

Ćwiklińska³

et al. 2022

JIR

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Introduction Identifying all the relevant “players” in the formation and development of brain aneurysms may help understand the mechanisms responsible for the formation of an aneurysm, as well as in the search for non-invasive targets for aneurysm pharmacotherapy. Aim The evaluation of the concentration of pro-inflammatory and anti-inflammatory cytokines in cerebrospinal fluid (CSF) and serum of patients with unruptured intracranial aneurysms (UIA) in comparison to individuals without vascular lesions in the brain. Methods The concentration of 27 proteins in the CSF and serum of UIA patients (N = 40) and individuals without vascular lesions in the brain (N = 15) was evaluated using a multiplex ELISA kit (Bio-Plex Pro Human Cytokine 27-Plex Panel). Results In the CSF 13 out of 27 proteins evaluated presented a concentration 1.36-fold or greater in UIA patients in comparison to the control group. Significantly higher were IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-7, IL-8, IL-12, IL-13, TNF-α, INF-γ, MCP-1, and VEGF. In the serum none of the proteins evaluated significantly differ between UIA patients and the control group. The correlation coefficient analysis showed that CSF IL-1β, IL-8, and TNF-α positively, while IL-13 negatively correlated with the size of aneurysms. CSF IL-6 and MCP-1 concentrations positively correlated with the number of aneurysms. Conclusion In patients with UIA, pro-inflammatory and anti-inflammatory mechanisms are activated simultaneously, because the concentration of promoting and suppressing inflammatory response proteins was significantly higher in CSF of UIA patients compared to the control group. The preventive therapy of brain aneurysm development should be focused on IL-1β, IL-6, IL-8, MCP-1, and TNF-α, the concentration of which in CSF positively correlated with the size and number of aneurysms.

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“…CUMS-induced depression is accompanied by neuro-inflammatory response. Peripheral cytokines can be involved in the pathways that affect the central synthesis of HPA hormones and neurotransmitters ( Serna-Rodríguez et al, 2022 ). TNF-α might contribute to the pathogenesis of depression by activation of the HPA axis.…”

Section: Discussionmentioning

confidence: 99%

Echinacoside exerts antidepressant-like effects through enhancing BDNF-CREB pathway and inhibiting neuroinflammation via regulating microglia M1/M2 polarization and JAK1/STAT3 pathway

Zhang

et al. 2023

Front. Pharmacol.

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The present study was performed to investigate the antidepressant effect of echinacoside (ECH) using chronic unpredictable mild stress (CUMS) induced depression mice and lipopolysaccharide (LPS)-stimulated N9 microglial cells. CUMS treatment was performed on C57BL/6 mice for 28 days, followed by gavaging with different doses of echinacoside (15 and 60 mg/kg) for 21 consecutive days. Sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were measured to assess the effects of echinacoside on CUMS-Induced Depressive-Like Behaviors. After that, the pathological changes of hippocampus were determined by Hematoxylin and eosin (HE) staining and Nissl staining; the neurotransmitters, pro-inflammatory cytokines and indoleamine 2,3-dioxygenase (IDO) levels, and the hypothalamic–pituitary–adrenal (HPA) axis activity were determined by enzyme linked immunosorbent assay (ELISA); Iba 1were evaluated by Immunofluorescence assay; Key protein expression levels of CREB/BDNF signal pathway were measured by western blotting. Subsequently, N9 cells were stimulated with 1 μg/ml LPS to induce N9 microglia activation, and were treated with 5–20 μM of echinacoside for 24 h. After that, the levels of NO, interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), IL-4, IL-10, and transforming growth factor beta (TGF-β) in N9 cell culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA) kits; morphology and Iba 1 expression level were observed by high-content screening assay; the M1 markers of CD11b, CD86 and M2 markers of CD206 were analyzed by imaging flow cytometry. Results show that treatment with echinacoside reversed CUMS-increased immobility time in OFT, TST, FST and reversed CUMS-reduced sucrose preference in SPT. In addition, echinacoside reduced the levels of pro-inflammatory cytokines and Iba 1. Moreover, echinacoside significantly increased p-CREB/CREB ratio and BDNF level in hippocampus. Furthermore, echinacoside reduced the secretion of inflammatory factors and inhibited microglia M1 polarization in N9 cells. In conclusion, echinacoside may be beneficial for the treatment of depression diseases through regulating the microglia balance by inhibiting the polarization of microglia to M1 phenotype, and improving hippocampal neurogenesis by the CREB-BDNF signaling pathway.

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The role of damage associated molecular pattern molecules (DAMPs) and permeability of the blood-brain barrier in depression and neuroinflammation

Cited by 41 publications

References 116 publications

Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment‐resistant depression following electroconvulsive therapy

Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment‐resistant depression following electroconvulsive therapy

Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients

Echinacoside exerts antidepressant-like effects through enhancing BDNF-CREB pathway and inhibiting neuroinflammation via regulating microglia M1/M2 polarization and JAK1/STAT3 pathway

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