Cytokine-induced sleep: Neurons respond to TNF with production of chemokines and increased expression of Homer1a in vitro

Karrer, Maureen; López, Martín; Meier, Daniel T.; Mikhail, Cyril; Ogunshola, Omolara O.; Müller, Andreas; Strauss, Laura; Tafti, Mehdi; Fontana, Adriano

doi:10.1016/j.bbi.2014.11.008

Cited by 20 publications

(14 citation statements)

References 49 publications

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“…This model is suggested by long-lasting elevation in cytokines even after the period of acute illness has passed. It is notable that both CCL2 and CXCL10, which are increased 50 days after CLP, have been shown in vitro to be induced by TNFα in immune and endothelial cells [ 73 , 74 ] and that TNFα also induces neuronal expression of these cytokines [ 75 ]. Conversely, CCR2 mediated signaling may potentiate release of TNFα from macrophages [ 76 ] and also contributes to dysfunction of the blood brain barrier [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Cecal Ligation and Puncture Results in Long-Term Central Nervous System Myeloid Inflammation

et al. 2016

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Survivors of sepsis often experience long-term cognitive and functional decline. Previous studies utilizing lipopolysaccharide injection and cecal ligation and puncture in rodent models of sepsis have demonstrated changes in depressive-like behavior and learning and memory after sepsis, as well as evidence of myeloid inflammation and cytokine expression in the brain, but the long-term course of neuroinflammation after sepsis remains unclear. Here, we utilize cecal ligation and puncture with greater than 80% survival as a model of sepsis. We found that sepsis survivor mice demonstrate deficits in extinction of conditioned fear, but no acquisition of fear conditioning, nearly two months after sepsis. These cognitive changes occur in the absence of neuronal loss or changes in synaptic density in the hippocampus. Sepsis also resulted in infiltration of monocytes and neutrophils into the CNS at least two weeks after sepsis in a CCR2 independent manner. Cellular inflammation is accompanied by long-term expression of pro-inflammatory cytokine and chemokine genes, including TNFα and CCR2 ligands, in whole brain homogenates. Gene expression analysis of microglia revealed that while microglia do express anti-microbial genes and damage-associated molecular pattern molecules of the S100A family of genes at least 2 weeks after sepsis, they do not express the cytokines observed in whole brain homogenates. Our results indicate that in a naturalistic model of infection, sepsis results in long-term neuroinflammation, and that this sustained inflammation is likely due to interactions among multiple cell types, including resident microglia and peripherally derived myeloid cells.

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Section: Discussionmentioning

confidence: 99%

Cecal Ligation and Puncture Results in Long-Term Central Nervous System Myeloid Inflammation

et al. 2016

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“…Some have speculated that this same signaling pathway may also mediate sleep-associated synaptic weakening. However, because the in vitro effects of TNFα on glutamatergic (Beattie et al, 2002 ; Karrer et al, 2015 ) and GABAergic (Stellwagen et al, 2005 ; Pribiag and Stellwagen, 2013 ) synapses are diverse, it remains unclear whether glial-derived TNFα signaling offers a plausible molecular mechanism for synaptic weakening during sleep.…”

Section: Part I: the Synaptic Homeostasis Hypothesismentioning

confidence: 99%

Linking Network Activity to Synaptic Plasticity during Sleep: Hypotheses and Recent Data

Puentes-Mestril

Aton

2017

Front. Neural Circuits

111

123

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Research findings over the past two decades have supported a link between sleep states and synaptic plasticity. Numerous mechanistic hypotheses have been put forth to explain this relationship. For example, multiple studies have shown structural alterations to synapses (including changes in synaptic volume, spine density, and receptor composition) indicative of synaptic weakening after a period of sleep. Direct measures of neuronal activity and synaptic strength support the idea that a period of sleep can reduce synaptic strength. This has led to the synaptic homeostasis hypothesis (SHY), which asserts that during slow wave sleep, synapses are downscaled throughout the brain to counteract net strengthening of network synapses during waking experience (e.g., during learning). However, neither the cellular mechanisms mediating these synaptic changes, nor the sleep-dependent activity changes driving those cellular events are well-defined. Here we discuss potential cellular and network dynamic mechanisms which could underlie reductions in synaptic strength during sleep. We also discuss recent findings demonstrating circuit-specific synaptic strengthening (rather than weakening) during sleep. Based on these data, we explore the hypothetical role of sleep-associated network activity patterns in driving synaptic strengthening. We propose an alternative to SHY—namely that depending on experience during prior wake, a variety of plasticity mechanisms may operate in the brain during sleep. We conclude that either synaptic strengthening or synaptic weakening can occur across sleep, depending on changes to specific neural circuits (such as gene expression and protein translation) induced by experiences in wake. Clarifying the mechanisms underlying these different forms of sleep-dependent plasticity will significantly advance our understanding of how sleep benefits various cognitive functions.

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“…TNFa also induces the neuronal production of chemokines, including CCL2 [104,105]. Ccl2 is typically upregulated during CNS virus infections and is a potent chemoattractant for Ly6C hi CCR2-bearing inflammatory monocytes [106][107][108][109] that can differentiate during viral encephalomyelitis into M1-type pro-inflammatory macrophages that express TNFa [108,110].…”

Section: Irf3à/à Mice Develop Fatal Disease After Infection With Wnvmentioning

confidence: 99%

Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis

Schultz

Troisi

Baxter

et al. 2019

Journal of General Virology

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Interferon (IFN) regulatory factors (IRFs) are important determinants of the innate response to infection. We evaluated the role(s) of combined and individual IRF deficiencies in the outcome of infection of C57BL/6 mice with Sindbis virus, an alphavirus that infects neurons and causes encephalomyelitis. The brain and spinal cord levels of Irf7, but not Irf3 mRNAs, were increased after infection. IRF3/5/7À/À and IRF3/7À/À mice died within 3-4 days with uncontrolled virus replication, similar to IFNa receptordeficient mice, while all wild-type (WT) mice recovered. IRF3À/À and IRF7À/À mice had brain levels of IFNa that were lower, but brain and spinal cord levels of IFNb and IFN-stimulated gene mRNAs that were similar to or higher than WT mice without detectable serum IFN or increases in Ifna or Ifnb mRNAs in the lymph nodes, indicating that the differences in outcome were not due to deficiencies in the central nervous system (CNS) type I IFN response. IRF3À/À mice developed persistent neurological deficits and had more spinal cord inflammation and higher CNS levels of Il1b and Ifng mRNAs than WT mice, but all mice survived. IRF7À/À mice died 5-8 days after infection with rapidly progressive paralysis and differed from both WT and IRF3À/À mice in the induction of higher CNS levels of IFNb, tumour necrosis factor (TNF) a and Cxcl13 mRNA, delayed virus clearance and more extensive cell death. Therefore, fatal disease in IRF7À/À mice is likely due to immune-mediated neurotoxicity associated with failure to regulate the production of inflammatory cytokines such as TNFa in the CNS.

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Cytokine-induced sleep: Neurons respond to TNF with production of chemokines and increased expression of Homer1a in vitro

Cited by 20 publications

References 49 publications

Cecal Ligation and Puncture Results in Long-Term Central Nervous System Myeloid Inflammation

Cecal Ligation and Puncture Results in Long-Term Central Nervous System Myeloid Inflammation

Linking Network Activity to Synaptic Plasticity during Sleep: Hypotheses and Recent Data

Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis

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