Neuronal ‘On’ and ‘Off’ signals control microglia

Biber, Knut; Neumann, Harald; Inoue, Kazuhide; Boddeke, Hendrikus

doi:10.1016/j.tins.2007.08.007

Cited by 697 publications

(583 citation statements)

References 73 publications

Supporting

Mentioning

557

Contrasting

Unclassified

Order By: Relevance

“…In this state, microglia rapidly switch to a ramified appearance, characterized by transcriptional and functional remodeling where P2X7 plays a critical role in IL-1ß release from LPS-primed microglia [40]. While in the healthy CNS, microglia normally exist in a quiescent state, characterized by a small soma and ramified processes where P2X7 receptor shows little or no functional activity [16,41]. In our study, it is a chronic and long-term active effect of morphine on microglia.…”

Section: Discussionmentioning

confidence: 62%

Morphine enhances IL-1β release through toll-like receptor 4-mediated endocytic pathway in microglia

Liang

Jiang

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

Morphine creates a neuroinflammatory response and enhances release of the proinflammatory cytokines like interleukin-1β (IL-1β), which compromises morphine analgesia as well as induces morphine tolerance. In this study, we attempted to investigate the mechanisms of morphine induced IL-1β synthesis and release. Microglial cells were treated with morphine (100 μM) once daily for 3 days. Control groups underwent the same procedure but received sterile saline injection instead of morphine. Toll-like receptor 4 (TLR4) and P2X4 receptor (P2X4R) signaling were analyzed using Western blot; immunofluorescence was used to detect the signaling of CD68; real-time RT-PCR and ELISA kit was used to measure the messenger RNA and protein synthesis and release level of IL-1β. Morphine enhanced IL-1β synthesis and P2X4R protein expression. TLR4 were responsible for morphine-induced IL-1β synthesis, while morphineinduced IL-1β release was via P2X4R. Morphineinduced IL-1β release is mediated by endocytosis of TLR4. These results indicated that TLR4 and P2X4R pathways mediated IL-1β synthesis and release in microglia followed chronic morphine. TLR4 internalization is the main mechanism of morphine-induced microglia activation and IL-1β release.

show abstract

Section: Discussionmentioning

confidence: 62%

Morphine enhances IL-1β release through toll-like receptor 4-mediated endocytic pathway in microglia

Liang

Jiang

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…In addition to these signaling principles that are initiated by the presence of exogenous factors that are not usually seen in the CNS or endogenous factors not normally seen at such concentrations (such as intracellular release of heat shock proteins), there are also a number of endogenous membranebound and secreted factors originating from neurons that influence microglial activity (Hanisch et al, 2007). These so called 'on' and 'off' signals that regulate microglial responses are extremely varied and beyond the scope of this review (see Biber et al, 2007). We focus in the sections that follow on the signaling pathways associated with Toll-like receptor (TLR) complexes, as these are the most extensively characterized receptors for host defense, as well as in the response to drugs of abuse (Gay et al, 2014;Trotta et al, 2014).…”

Section: Microgliamentioning

confidence: 99%

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

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

218

170

View full text Add to dashboard Cite

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.

show abstract

“…42,43 Thus, we determined the neuronal response to rotenone exposure in the presence of primary glia with or without MPO. Primary mesencephalic neuron-enriched cultures from WT mice were incubated with glial cells from Mpo Ϫ/Ϫ or WT mice using transwell chambers, after which the extent of neuronal cell death was determined using LDH analysis and CCK-8.…”

Section: Rotenone-triggered Neuronal Injury Is More Apparent In Co-cumentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOClproducing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo ؊/؊ mice than in those from wildtype mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.

show abstract

Neuronal ‘On’ and ‘Off’ signals control microglia

Cited by 697 publications

References 73 publications

Morphine enhances IL-1β release through toll-like receptor 4-mediated endocytic pathway in microglia

Morphine enhances IL-1β release through toll-like receptor 4-mediated endocytic pathway in microglia

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

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Contact Info

Product

Resources

About