Association between toll-like receptors expression and major depressive disorder

Hung, Yi-Yung; Kang, Hong-Yo; Huang, Kuan-Gen; Huang, Tiao‐Lai

doi:10.1016/j.psychres.2014.07.074

Cited by 90 publications

(75 citation statements)

References 38 publications

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“…Molecular pathway analysis both on mRNA and microRNA levels revealed that apoptosis, cell-cell communication, adhesion and immune function related transcripts were significantly altered in the MD samples. These results were consistent with the previous postmortem and in vivo findings (Shelton et al, 2011, Hung et al, 2014), and provided further validation of transcriptome similarities between the brain and peripheral tissue of patients with MD.…”

Section: Understanding Pathophysiological Processes Using Hdfssupporting

confidence: 91%

Human dermal fibroblasts in psychiatry research

et al. 2016

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Summary In order to decipher the disease etiology, progression and treatment of multifactorial human brain diseases we utilize a host of different experimental models. Recently, patient-derived human dermal fibroblast (HDF) cultures have re-emerged as promising in vitro functional system for examining various cellular, molecular, metabolic and (patho)physiological states and traits of psychiatric disorders. HDF studies serve as a powerful complement to postmortem and animal studies, and often appear to be informative about the altered homeostasis in neural tissue. Studies of HDFs from patients with schizophrenia, depression, bipolar disorder, autism, attention deficit and hyperactivity disorder and other psychiatric disorders have significantly advanced our understanding of these devastating diseases. These reports unequivocally prove that signal transduction, redox homeostasis, circadian rhythms and gene*environment interactions are all amenable for assessment by the HDF model. Furthermore, the reported findings suggest that this underutilized patient biomaterial, combined with modern molecular biology techniques, may have both diagnostic and prognostic value, including prediction of response to therapeutic agents.

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Section: Understanding Pathophysiological Processes Using Hdfssupporting

confidence: 91%

Human dermal fibroblasts in psychiatry research

et al. 2016

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“…The levels of the TLRs have also been studied in the blood of depressed patients by Hung et al (2014). They found that the mRNA levels of TLR3, TLR4, TLR5 and TLR7 were significantly increased in the peripheral blood of depressed patients, but had lower expression of TLR1and TLR6 in patients with major depression.…”

Section: Discussionmentioning

confidence: 99%

Innate immunity in the postmortem brain of depressed and suicide subjects: Role of Toll-like receptors

Pandey

Rizavi

Bhaumik

et al. 2019

Brain, Behavior, and Immunity

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Abnormalities of Toll-like receptors (TLRs) have been implicated in the pathophysiology of depression and suicide. Interactions of TLRs with pathogen-associated molecular patterns (PAMP) and damage-associated molecular patterns (DAMP) initiate signaling through myeloid differentiation primary response-88 (MyD88) and produce cytokines through the activation of the transcription factor nuclear factor kappa beta (NF-kB). We have earlier shown an increase in the protein and mRNA expression of TLR3 and TLR4 in the prefrontal cortex (PFC) of depressed suicide (DS) subjects compared with normal control (NC) subjects. To examine if other TLRs are altered in postmortem brain, we have now determined the protein and mRNA expression of other TLRs (TLR1, TLR2, TLR5, TLR6, TLR7, TLR8, TLR9 and TLR10) in the PFC of DS, depressed non-suicide (DNS), non-depressed suicide (NDS) and NC subjects. We determined the protein expression by Western blot and mRNA expression levels by real-time PCR (qPCR) in the PFC of 24 NC, 24 DS, 12 DNS and 11 NDS subjects. Combined with our previous study of TLR3 and TLR4, we found that the protein expression of TLR2, TLR3, TLR4, TLR6 and TLR10, and mRNA expression of TLR2 and TLR3 was significantly increased in the DS group compared with NC group. This study demonstrated that certain specific TLRs are altered in DS subjects, and hence those TLRs may be appropriate targets for the development of therapeutic agents for the treatment of suicidal behavior.

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“…activation of cell-mediated immunity (CMI), including T cell activation, e.g. a T helper (Th)1 shift [9]; activation of oxidative stress pathways [10][11][12]; decreased levels of key antioxidants, including coenzyme Q10 [12,13]; hypernitrosylation [12,14]; autoimmune responses directed against oxidative and nitroso-specific epitopes [12,14]; increased bacterial translocation followed by increased immune responses to lipopolysaccharides (LPS) of gram negative bacteria [15]; and activation of the Toll-like Receptor (TLR) 2/4 Radical Cycle [16][17][18][19].…”

Section: Inflammation Is Not the Only Drug Target In Depressionmentioning

confidence: 99%

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

et al. 2015

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Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g. C-reactive protein, and pro-inflammatory cytokines, e.g. interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways.Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g. activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, activation of the Toll-like Receptor and neuroprogressive pathways. Thirdly, antiinflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e. path and drug discovery processes, omics-based techniques and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics and microbiomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular 4 networks, pathways and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.

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Association between toll-like receptors expression and major depressive disorder

Cited by 90 publications

References 38 publications

Human dermal fibroblasts in psychiatry research

Human dermal fibroblasts in psychiatry research

Innate immunity in the postmortem brain of depressed and suicide subjects: Role of Toll-like receptors

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

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