CRF-Amplified Neuronal TLR4/MCP-1 Signaling Regulates Alcohol Self-Administration

June, Harry L.; Liu, Juan; Warnock, Kaitlin T.; Bell, Kimberly; Balan, Irina; Bollino, Dominique; Puché, Adam C.; Aurelian, Laure

doi:10.1038/npp.2015.4

Cited by 92 publications

(148 citation statements)

References 60 publications

(99 reference statements)

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“…Viral mediated delivery of siRNA to knockdown expression of TLR4 in the central amygdala was found to inhibit binge drinking in rats (Liu et al, 2011). In a similar fashion, delivery of siRNA against either TLR4 or CCL2 into the VTA produced a reduction in voluntary alcohol consumption in rats, while consumption of sucrose was unaffected (June et al, 2015). Although these results suggest a potential role for both TLR4 and TLR2, there are still many questions that remain regarding their relative contributions to neuroimmune signaling cascades induced by alcohol.…”

Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 72%

“…Nonetheless, not all TLRs are localized exclusively on microglia. TLR4, for example, has been observed on microglia, neurons, astrocytes, neural progenitor cells, and endothelial cells (AlfonsoLoeches et al, 2010;Grace et al, 2014b;Jack et al, 2005;June et al, 2015;Liu et al, 2011;Rolls et al, 2007). Advanced transcriptome analysis of purified cell populations in rodent cortex confirms that these other cells have transcript copies for TLR4 .…”

Section: Microgliamentioning

confidence: 78%

“…In alcohol-preferring rats, self-administration of alcohol is associated with increased TLR4 protein expression in the VTA, but not ventral pallidum (June et al, 2015). Several members of the receptor complex-TLR4, MD-2, and CD14-are critical for alcohol-induced activation of astrocytes in culture, as small interfering RNA (siRNA) to knockdown expression of any of these three targets prevented nuclear translocation of the NF-κB-p65 subunit in response to alcohol (Alfonso-Loeches et al, 2010).…”

Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 99%

See 2 more Smart Citations

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

218

170

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Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders.

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Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 72%

Section: Microgliamentioning

confidence: 78%

Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

218

170

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“…Similarly, stimulation PPARγ that is expressed in microglia also reduce alcohol drinking in a 3-h and 24-h two-bottle choice paradigm and a drinking-in-the-dark procedure, potentially through the anti-inflammatory properties of PPARγ agonists (Blednov et al, 2015; Ferguson et al, 2014; Stopponi et al, 2013). Self-administration of alcohol is also associated with increased TLR4 protein expression in the ventral tegmental area of alcohol preferring P rats (June et al, 2015). The C3H/HeJ mouse strain possesses a TLR4 point mutation that can disrupt TLR4 signaling.…”

Section: Drugs Of Abuse and Glial Cell Activitymentioning

confidence: 99%

Glial and neuroinflammatory targets for treating substance use disorders

Bachtell

Jones

Heinzerling

et al. 2017

Drug and Alcohol Dependence

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Background The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders. Methods Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders. Results Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders. Conclusions The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

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“…26 Furthermore, in preclinical models global knockout and selective knockout (via siRNA) of immune receptors and related molecules attenuate addiction-like behaviours such as impulsive consumption and craving. 27,28 Drugs of abuse act at the cellular, receptor and molecular level, engaging multiple overlapping neuroimmune pathways. However, it is important to appreciate that these systems do not work in isolation.…”

Section: Evidence For Neuroimmune System Involvement In Addictionmentioning

confidence: 99%

Drug addiction: targeting dynamic neuroimmune receptor interactions as a potential therapeutic strategy

Jacobsen

Hutchinson

Mustafa

2016

Current Opinion in Pharmacology

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After the embargo period via non-commercial hosting platforms such as their institutional repository  via commercial sites with which Elsevier has an agreement In all cases accepted manuscripts should: link to the formal publication via its DOI  bear a CC-BY-NC-ND license -this is easy to do, click here to find out how  if aggregated with other manuscripts, for example in a repository or other site, be shared in alignment with our hosting policy  not be added to or enhanced in any way to appear more like, or to substitute for, the published journal article Embargo 1471-4892 Current Opinion in Pharmacology 12months6 March 2017 Highlights• Drugs of abuse activate the neuroimmune system• The neuroimmune system is pivotal to the progression of addiction• Multiple independent parallel systems are not sufficient to explain complex states• Integrated signalling networks are crucial for addictive behaviours• Targeting receptor interactions may offer a novel therapeutic intervention AbstractDrug addiction and dependence have proven to be difficult psychiatric disorders to treat. The limited efficacy of neuronally-acting medication such as, acamprosate and naltrexone, highlights the need to identify novel targets. Recent research has underscored the importance of the neuroimmune system in many behavioural manifestations of drug addiction. In this review, we propose that our appreciation for complex phenotypes such as drug addiction and dependence will come with a greater understanding that these disorders are the result of intricate, interconnected signalling pathways that are, if only partially, determined at the receptor level. The idea of receptor heteromerisation and receptor mosaics will be introduced to explain cross talk between the receptors and signalling molecules implicated in neuroimmune signalling pathways.

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CRF-Amplified Neuronal TLR4/MCP-1 Signaling Regulates Alcohol Self-Administration

Cited by 92 publications

References 60 publications

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Glial and neuroinflammatory targets for treating substance use disorders

Drug addiction: targeting dynamic neuroimmune receptor interactions as a potential therapeutic strategy

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