Activation of TLR4/STAT3 signaling in VTA contributes to the acquisition and maintenance of morphine-induced conditioned place preference

Chen, Jiaxin; Huang, Kang-Mei; Li, Meng; Jiang, Jinxiang; Jianpeng, Liu; Zhang, Yuxiang; Chen, Yang; Xin, Wenjun; Zhang, Xueqin

doi:10.1016/j.bbr.2017.08.022

Cited by 31 publications

(13 citation statements)

References 32 publications

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“…The immunoblotting assay demonstrated that expression of TLR4 and its downstream molecules was inhibited by geniposide in HCC cells, including MyD88, p‐p38 MAPK, p65 and IκB‐α (Figure 5c,d). As the alteration of TLR4/MyD88 expression is commonly linked to the downstream regulation of STAT3 and Sp1 (J. X. Chen et al, 2017; Xiao et al, 2017), we examined if reactivation of TLR4 by its agonist LPS could reverse geniposide‐induced inhibition of STAT3 and Sp1 in HCC cells. Our experiments showed that LPS restored the expression of TLR4 and MyD88.…”

Section: Resultsmentioning

confidence: 99%

Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF‐1α‐independent VEGF expression and angiogenesis in hepatocellular carcinoma

Zhang

Wang

Tan

et al. 2020

British J Pharmacology

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Background and Purpose: As a typical hypervascular tumour, hepatocellular carcinoma (HCC) is predominantly grown through angiogenesis. Geniposide is a promising anti-inflammatory compound found in Gardenia jasminoides, but its effects on the progression of HCC remain untested. Experimental Approach: The anti-HCC effects of geniposide was investigated in cellular models and orthotopic HCC mice. Transcriptional regulation of the VEGF promoter was measured by dual-luciferase reporter assay. The anti-angiogenic action of geniposide was measured by tube formation assay. Both surface plasmon resonance techniques and human phospho-kinase array analysis were utilized to validate the relationship between targets of geniposide and hepatocarcinogenesis. Key Results: Geniposide exhibited significant disruption of HCC proliferation, invasion, angiogenesis and lung metastasis in orthotopic HCC mice. Geniposide inhibited secretion of VEGF by HCC and suppressed the migration of endothelial cells and the formation of intra-tumour blood vessels, without cytotoxicity and independently of the transcription factor HIF-1α. Direct inhibition of TLR4 by geniposide led to the shutdown of the TLR4/MyD88 pathway and STAT3/Sp1-dependent VEGF production. However, LPS, an agonist of TLR4, restored STAT3/Sp1-related VEGF production in geniposide-inhibited HCC angiogenesis. Conclusion and Implications: The direct inhibitory effect of geniposide on TLR4/ MyD88 activation contributes to the suppression of STAT3/Sp1-dependent VEGF overexpression in HCC angiogenesis and pulmonary metastasis. This action of geniposide was not affected by stabilization of HIF-1α. Our study offers a novel anti-VEGF mechanism for the inhibition of HCC.

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Section: Resultsmentioning

confidence: 99%

Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF‐1α‐independent VEGF expression and angiogenesis in hepatocellular carcinoma

Zhang

Wang

Tan

et al. 2020

British J Pharmacology

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“…PTPRD-mediated changes in the phosphorylation of STAT3 Y705 phosphotyrosine alter the ability of this transcription factor to homodimerize, move into the nucleus, and change transcription of other genes (36). Acute changes in tyrosine phosphorylation provide plausible mechanisms for influencing drug reward; both Cdk5 and STAT3 activities have been implicated in addictions (42,43). There is thus now a substantial rationale for optimizing 7-BIArelated structures and advancing improved PTPRD phosphatase inhibitors to clinical testing for substance use disorders.…”

Section: Discussionmentioning

confidence: 99%

Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist

Uhl

Martínez

Paik

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Receptor-type protein tyrosine phosphatase D (PTPRD) is a neuronal cell-adhesion molecule/synaptic specifier that has been implicated in addiction vulnerability and stimulant reward by human genomewide association and mouse cocaine-conditioned place-preference data. However, there have been no reports of effects of reduced expression on cocaine self-administration. There have been no reports of PTPRD targeting by any small molecule. There are no data about behavioral effects of any PTPRD ligand. We now report (i) robust effects of heterozygous PTPRD KO on cocaine self-administration (These data substantially extend prior conditioned place-preference data and add to the rationale for PTPRD as a target for addiction therapeutics.); (ii) identification of 7-butoxy illudalic acid analog (7-BIA) as a small molecule that targets PTPRD and inhibits its phosphatase with some specificity; (iii) lack of toxicity when 7-BIA is administered to mice acutely or with repeated dosing; (iv) reduced cocaine-conditioned place preference when 7-BIA is administered before conditioning sessions; and (v) reductions in well-established cocaine self-administration when 7-BIA is administered before a session (in WT, not PTPRD heterozygous KOs). These results add to support for PTPRD as a target for medications to combat cocaine use disorders. 7-BIA provides a lead compound for addiction therapeutics.

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“…As evidenced above, morphine CPP is regulated by glutamatergic, cholinergic, and dopaminergic systems. In addition to this, preclinical evidence suggests that morphine-context associations rely on signaling from another neurotransmitter, hormonal, and neuromodulatory systems, including opioid, GABA, norepinephrine, serotonin, cannabinoid, nitric oxide, hypocretin/orexin, neuropeptide S, and cholecystokinin (Tzschentke, 1998 , 2007 ; Le Merrer et al, 2009 ; Li et al, 2009 ; Billa et al, 2010 ; Karimi et al, 2013 ; Ghavipanjeh et al, 2015 ; Loureiro et al, 2016 ; Zhang et al, 2016 ; Azizbeigi et al, 2019 ) as well as systems involved in immune function and inflammation (Ghahremani et al, 2006 ; Zhang et al, 2012 ; Chen et al, 2017 ). Additionally, evidence suggests that morphine-induced suppression of endogenous histamine is important for morphine CPP as bilateral lesions of the tuberomammillary nucleus, a brain region that expresses histamine-releasing neurons, potentiated the development of morphine CPP (Gong et al, 2007 ).…”

Section: Neurobiology Of Drug-induced Cpp: Focus On Opioid Cppmentioning

confidence: 99%

Drug-Induced Conditioned Place Preference and Its Practical Use in Substance Use Disorder Research

McKendrick

Graziane

2020

Front. Behav. Neurosci.

128

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The conditioned place preference (CPP) paradigm is a well-established model utilized to study the role of context associations in reward-related behaviors, including both natural rewards and drugs of abuse. In this review article, we discuss the basic history, various uses, and considerations that are tied to this technique. There are many potential takeaway implications of this model, including negative affective states, conditioned drug effects, memory, and motivation, which are all considered here. We also discuss the neurobiology of CPP including relevant brain regions, molecular signaling cascades, and neuromodulatory systems. We further examine some of our prior findings and how they integrate CPP with self-administration paradigms. Overall, by describing the fundamentals of CPP, findings from the past few decades, and implications of using CPP as a research paradigm, we have endeavored to support the case that the CPP method is specifically advantageous for studying the role of a form of Pavlovian learning that associates drug use with the surrounding environment.

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Activation of TLR4/STAT3 signaling in VTA contributes to the acquisition and maintenance of morphine-induced conditioned place preference

Cited by 31 publications

References 32 publications

Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF‐1α‐independent VEGF expression and angiogenesis in hepatocellular carcinoma

Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF‐1α‐independent VEGF expression and angiogenesis in hepatocellular carcinoma

Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist

Drug-Induced Conditioned Place Preference and Its Practical Use in Substance Use Disorder Research

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