Neurodegeneration by Activation of the Microglial Complement-Phagosome Pathway

Bodea, Liviu‐Gabriel; Wang, Yiner; Linnartz‐Gerlach, Bettina; Kopatz, Jens; Sinkkonen, Lasse; Musgrove, Ruth E.; Kaoma, Tony; Muller, Arnaud; Vallar, Laurent; Monte, Donato A. Di; Balling, Rudi; Neumann, Harald

doi:10.1523/jneurosci.5002-13.2014

Cited by 184 publications

(184 citation statements)

References 47 publications

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…The induction of a chronic inflammatory state by repeated LPS injections may be a more reliable method to test the effects of environmental changes, such as changes in diet or ambient temperature, e.g, on immune responses of pigs (67). This assumption is supported by a recent study that found that, compared with a single LPS injection, repeated injections of LPS resulted in higher brain proinflammatory cytokine responses in rats (68).…”

Section: Discussionmentioning

confidence: 94%

Maternal Fish Oil Supplementation Affects the Social Behavior, Brain Fatty Acid Profile, and Sickness Response of Piglets

Clouard

Souza

Gerrits

et al. 2015

The Journal of Nutrition

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 94%

Maternal Fish Oil Supplementation Affects the Social Behavior, Brain Fatty Acid Profile, and Sickness Response of Piglets

Clouard

Souza

Gerrits

et al. 2015

The Journal of Nutrition

View full text Add to dashboard Cite

show abstract

“…They comprise cytokines (Buffo et al 2010;Falsig et al 2004a;Garwood et al 2011); lipocalin 2 (Bi et al 2013), components of the complement system (Bodea et al 2014;Pekny et al 2007), or changes due to altered ATPase expression (Gallardo et al 2014). Besides these mostly proteinaceaous molecules, also some small molecules with cell death-inducing properties have been described.…”

Section: Discussionmentioning

confidence: 99%

Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation

et al. 2016

View full text Add to dashboard Cite

were involved in this neurodegeneration. The neurotoxicity-mediating effect of IMA was faithfully reproduced by human astrocytes. Moreover, glia-dependent toxicity was also observed, when IMA cultures were stimulated with CM, and the culture medium was transferred to neurons. Such neurotoxicity was prevented when astrocytes were treated by p38 kinase inhibitors or dexamethasone, whereas such compounds had no effect when added to neurons. Conversely, treatment of neurons with five different drugs, including resveratrol and CEP1347, prevented toxicity of astrocyte supernatants. Thus, the sequential IMA-LUHMES neuroinflammation model is suitable for separate profiling of both glial-directed and directly neuroprotective strategies. Moreover, direct evaluation in co-cultures of the same cells allows for testing of therapeutic effectiveness in more complex settings, in which astrocytes affect pharmacological properties of neurons.Keywords LUHMES · Astrocyte · p38 kinase · Neuroinflammation · Neuropharmacology Abstract Astrocytes, the largest cell population in the human brain, are powerful inflammatory effectors. Several studies have examined the interaction of activated astrocytes with neurons, but little is known yet about human neurotoxicity under such situations and about strategies of neuronal rescue. To address this question, immortalized murine astrocytes (IMA) were combined with human LUHMES neurons and stimulated with an inflammatory (TNF, IL-1) cytokine mix (CM). Neurotoxicity was studied both in co-cultures and in monocultures after transfer of conditioned medium from activated IMA. Interventions with >20 drugs were used to profile the model system. Control IMA supported neurons and protected them from neurotoxicants. Inflammatory activation reduced this protection, and prolonged exposure of co-cultures to CM triggered neurotoxicity. Neither the added cytokines nor the release of NO from astrocytes Liudmila Efremova and Petra Chovancova have contributed equally to this study.

show abstract

“…It has been corroborated that microglia can be primed toward a pro-inflammatory state by the C3 receptor [85]. An in vivo study that continually induced a microglial inflammatory phenotype in mice, using lipopolysaccharide (LPS), showed an activation of the microglial complement-phagosome pathway that subsequently induced neurodegeneration [86]. …”

Section: Microglia and Neuroinflammation: Beneficial And Detrimentmentioning

confidence: 99%

Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins

Swanson

Wolf

Sitzmann

et al. 2018

Behavioural Brain Research

View full text Add to dashboard Cite

Neuroinflammation is a potential factor speculated to underlie Alzheimer’s disease (AD) etiopathogenesis and progression. The overwhelming focus in this area of research to date has been on the chronic upregulation of pro-inflammatory cytokines to understand how neuroinflammatory mechanisms contribute to neurodegeneration. Yet, it is important to understand the pleiotropic roles of these cytokines in modulating neuroinflammation in which they cannot be labeled as a strictly “good” or “bad” biomarker phenotype. As such, biomarkers with more precise functions are needed to better understand how neuroinflammation impacts the brain in AD. Neuronal pentraxins are a concentration- dependent group of pro- or anti- inflammatory cytokines. There is contradictory evidence of these pentraxins as being both neuroprotective and potentially detrimental in AD. Potential neuroprotective examples include their ability to predict AD-related outcomes such as cognition, memory function and synaptic refinement. This review will briefly outline the basis of AD and subsequently summarize findings for neuropathological mechanisms of neuroinflammation, roles for traditional pro-and anti-inflammatory cytokines, and data found thus far on the neuronal pentraxins.

show abstract

Neurodegeneration by Activation of the Microglial Complement-Phagosome Pathway

Cited by 184 publications

References 47 publications

Maternal Fish Oil Supplementation Affects the Social Behavior, Brain Fatty Acid Profile, and Sickness Response of Piglets

Maternal Fish Oil Supplementation Affects the Social Behavior, Brain Fatty Acid Profile, and Sickness Response of Piglets

Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation

Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins

Contact Info

Product

Resources

About