The Role of Brain Interleukin-1 in Stress-Enhanced Fear Learning

Jones, Meghan E.; Lebonville, Christina L.; Barrus, Daniel; Lysle, Donald T.

doi:10.1038/npp.2014.317

Cited by 72 publications

(91 citation statements)

References 53 publications

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“…Although these secreted molecules can aid in host defense against invading pathogens, many are neurotoxic and must be quickly inactivated upon pathogen clearance to prevent neuronal injury. For example, an imbalance of pro-inflammatory cytokines is implicated in numerous neurodegenerative diseases and is considered detrimental for cognition (Jones et al, 2015;Kilic et al, 2008;Williamson et al, 2011). Taken together, there is growing evidence that TLR-induced inflammatory products impact not only immune signaling, but also behavior.…”

Section: Microgliamentioning

confidence: 99%

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

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

223

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: Microgliamentioning

confidence: 99%

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

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

223

170

View full text Add to dashboard Cite

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“…Moreover, whether the success of these interventions is in part due to inhibition of stress-induced inflammatory responses or even through glucocorticoid-mediated trafficking of neuroprotective T cells to the brain has yet to be established. Interestingly, recent laboratory animal data suggest that blockade of IL-1 can reduce stress-enhanced fear learning in an animal model of PTSD (Jones et al, 2015). Clearly, more work on the role of inflammatory pathways in the development and treatment of fear and anxiety-related disorders in the context of trauma is warranted.…”

Section: Reviewmentioning

confidence: 99%

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

Miller

Haroon

Felger

2016

Neuropsychopharmacol

118

124

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A wealth of data has been amassed that details a complex, yet accessible, series of pathways by which the immune system, notably inflammation, can influence the brain and behavior. These data have opened the window to a diverse array of novel targets whose potential efficacy is tied to specific neurotransmitters and neurocircuits as well as specific behaviors. What is clear is that the impact of inflammation on the brain cuts across psychiatric disorders and engages dopaminergic and glutamatergic pathways that regulate motivation and motor activity as well as the sensitivity to threat. Given the ability to identify patient populations with increased inflammation, the precision of interventions can be further tuned, in conjunction with the ability to establish target engagement in the brain through the use of multiple neuroimaging strategies. After a brief overview of the mechanisms by which inflammation affects the brain and behavior, this review examines the extant literature on the efficacy of anti-inflammatory treatments, while forging guidelines for future intelligent clinical trial design. An examination of the most promising therapeutic strategies is also provided, along with some of the most exciting clinical trials that are currently being planned or underway.

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“…Chronic morphine has been shown to elevate astrocyte activation in the hippocampus (Song and Zhao, 2001), but again, it is unclear whether this would occur following five doses of heroin or whether this would lead to increased release of IL-1β. Stress-induced IL-1β expression was reduced in the dentate gyrus by morphine (Jones et al, 2015), indicating that opioids may have differential effects in different subregions of the hippocampus or that opioid action might depend on prior inflammatory states.…”

Section: Discussionmentioning

confidence: 99%

Acquisition of heroin conditioned immunosuppression requires IL-1 signaling in the dorsal hippocampus

Lebonville

Jones

Hutson

et al. 2016

Brain, Behavior, and Immunity

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Opioid users experience increased incidence of infection, which may be partially attributable to both direct opiate-immune interactions and conditioned immune responses. Previous studies have investigated the neural circuitry governing opioid conditioned immune responses, but work remains to elucidate the mechanisms mediating this effect. Our laboratory has previously shown that hippocampal IL-1 signaling, specifically, is required for the expression of heroin conditioned immunosuppression following learning. The current studies were designed to further characterize the role of hippocampal IL-1 in this phenomenon by manipulating IL-1 during learning. Experiment 1 tested whether hippocampal IL-1 is also required for the acquisition of heroin conditioned immunosuppression, while Experiment 2 tested whether hippocampal IL-1 is required for the expression of unconditioned heroin immunosuppression. We found that blocking IL-1 signaling in the dorsal hippocampus with IL-1RA during each conditioning session, but not on interspersed non-conditioning days, significantly attenuated the acquisition of heroin conditioned immunosuppression. Strikingly, we found that the same IL-1RA treatment did not alter unconditioned immunosuppression to a single dose of heroin. Thus, IL-1 signaling is not a critical component of the response to heroin but rather may play a role in the formation of the association between heroin and the context. Collectively, these studies suggest that IL-1 signaling, in addition to being involved in the expression of a heroin conditioned immune response, is also involved in the acquisition of this effect. Importantly, this effect is likely not due to blocking the response to the unconditioned stimulus since IL-1RA did not affect heroin’s immunosuppressive effects.

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The Role of Brain Interleukin-1 in Stress-Enhanced Fear Learning

Cited by 72 publications

References 53 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

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

Acquisition of heroin conditioned immunosuppression requires IL-1 signaling in the dorsal hippocampus

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