scholarly journals Exercise conditioned plasma dampens inflammation via clusterin and boosts memory

2019 ◽  
Author(s):  
Zurine De Miguel ◽  
Michael J. Betley ◽  
Drew Willoughby ◽  
Benoit Lehallier ◽  
Niclas Olsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Aging ◽  
Animal Health ◽  
Brain Inflammation ◽  
Cognitively Impaired ◽  
Complement Cascade ◽  
Striking Increase ◽  
Cognitive Benefits ◽  
Anti Inflammatory ◽  
The Brain

Physical exercise seems universally beneficial to human and animal health, slowing cognitive aging and neurodegeneration. Cognitive benefits are tied to increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms mediating these effects. We discovered “runner” plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and prominently suppresses experimentally induced brain inflammation. Plasma proteomic analysis shows a striking increase in complement cascade inhibitors including clusterin, which is necessary for the anti-inflammatory effects of runner plasma. Cognitively impaired patients participating in structured exercise for 6 months showed higher plasma clusterin levels, which correlated positively with improvements in endurance and aerobic capacity. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferrable, benefit the brain, and are present in humans engaging in exercise.

Death receptors on reactive astrocytes

Neurology ◽  
2003 ◽  
Vol 60 (4) ◽  
pp. 548-554 ◽  
Author(s):  
Pierre-Yves Dietrich ◽  
Paul R. Walker ◽  
Philippe Saas
Keyword(s):  
Brain Injury ◽  
Immune Responses ◽  
Death Receptors ◽  
Reactive Astrocytes ◽  
Brain Inflammation ◽  
Fine Tuning ◽  
Immune Mediated ◽  
Anti Inflammatory ◽  
The Brain

Immune responses protect the CNS against pathogens. However, the fact that there is little dispensable tissue in the brain makes regulation necessary to avoid disastrous immune-mediated damage. Astrocytes respond vigorously to any brain injury (e.g., tumor, stroke, AD, MS, HIV) and are postulated to play an important role in the fine tuning of brain inflammation. The authors propose that astrocytes use death receptors to modulate pro- and anti-inflammatory effects.

scholarly journals Royal Jelly Acid, 10-Hydroxy-Trans-2-Decenoic Acid,for Psychiatric and Neurological Disorders: How helpful could it be?!

2019 ◽  
pp. 1-4 ◽  
Author(s):  
Mohammed Ali Amira ◽  
Omar Hendawy Amin
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Molecular Mechanism ◽  
Neurological Disorders ◽  
Royal Jelly ◽  
Decenoic Acid ◽  
Lipid Component ◽  
Main Fatty Acid ◽  
Anti Inflammatory ◽  
The Brain

10-hydroxy-trans-2-decenoic acid (10H2DA), also known as royal jelly acid, is the main lipid component of RJ. It possesses anti-tumor, neurogenic, anti-inflammatory, antioxidant, bactericidal, nematocidal, and estrogen-like properties. A limited number of studies demonstrate the potentials of its main fatty acid, 10-H2DA, for alleviating anxiety and depressive-like behaviors as well as for enhancing neuronal functioning. However, the exact mechanism through which 10-H2DA produces its effect is not well-understood. This mini review gives examples of how 10H2DA might positively contribute to the treatment of psychiatric and neurological disorders. In addition, it surveys the available knowledge about the molecular mechanism through which it regulates transcriptional processes and gene expression in the brain.

Carrageenan-induced brain inflammation

1986 ◽  
Vol 65 (5) ◽  
pp. 679-685 ◽  
Author(s):  
Daniel A. Gamache ◽  
John T. Povlishock ◽  
Earl F. Ellis
Keyword(s):  
Arachidonic Acid ◽  
Vascular Permeability ◽  
Brain Inflammation ◽  
Intraventricular Injection ◽  
Arachidonic Acid Metabolite ◽  
Maximum Increase ◽  
Peripheral Tissues ◽  
Neutrophil Extravasation ◽  
Anti Inflammatory ◽  
The Brain

✓ Administration of the mucopolysaccharide, carrageenan (CAR), into the hind paw of the rat or mouse induces a local inflammation characterized by increased arachidonic acid metabolism, increased vascular permeability, edema, and neutrophil extravasation. Carrageenan-induced hind-paw inflammation is inhibited by prostaglandin synthesis inhibitors, and this assay predicts the clinical success of anti-inflammatory agents in reducing peripheral inflammation. The purpose of this study was to determine if intraventricular injection of CAR would induce brain inflammation similar to that evoked by CAR in peripheral tissues. The present study demonstrates that CAR injection into the ventricles of the mouse brain does in fact induce an inflammatory response very similar to that caused by injection of CAR into the peripheral tissues. The brain response to CAR was dose-dependent, with the maximum increase in cerebrovascular permeability to iodine-125-labeled human serum albumin and percent brain water occurring after injection of 50 µg CAR. As is seen in CAR-induced inflammation of the hind paw, the maximum increase in brain vascular permeability occurred 4 hours after CAR injection. Histological analysis of brains 4 hours after CAR administration showed global neutrophil extravasation into the subarachnoid space and evidence of focal neuronal swelling. Methotrexate-induced neutropenia, however, failed to diminish the permeability response to CAR. Gas chromatographic and mass spectrometric measurements of brain prostaglandins 4 hours after CAR injection revealed a significantly increased level of 6-keto-prostaglandin F1α. These results indicate that a significant increase in prostacyclin, the pro-inflammatory arachidonic acid metabolite, during CAR-induced brain inflammation is likely. These studies suggest that CAR-induced brain inflammation may be a useful model on which to test the efficacy of anti-inflammatory agents in the brain, as well as providing information concerning the mediators and mechanisms by which the brain may sustain inflammatory injury.

scholarly journals 4R-Cembranoid Treatment Alters Gene Expression of RAW264.7 Macrophages in Basal and Inflammatory Conditions

2020 ◽  
Author(s):  
Maxine N. Gonzalez-Vega ◽  
Sandeep sreerama ◽  
Kelvin Carrasquillo-Carrion ◽  
Abiel Roche-Lima ◽  
Susan Corey Best ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Parenchyma ◽  
Inflammatory Conditions ◽  
Raw264.7 Macrophages ◽  
Blood Brain Barrier Model ◽  
Peripheral Immune Response ◽  
Anti Inflammatory ◽  
Macrophage Adhesion ◽  
The Brain ◽  
Inflammatory Effect

Inflammation is considered an important target for stroke therapy because it induces secondary brain damage after the initial ischemic insult. Peripheral monocytes migrate to the brain parenchyma after a central insult. They then differentiate to macrophages in a positive feedback fashion contributing to damage instead of ischemic resolution and inflammation control. A cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R), decreases neurodegeneration after ischemia with central anti-inflammatory activity. This study aims to determine whether the central anti-inflammatory effect of 4R is effective against peripheral inflammation triggered by brain ischemia. To investigate the anti-inflammatory effect of 4R, we treated macrophages with lipopolysaccharide (LPS) as an inflammatory model, followed by treatment with 4R. Microarray transcriptome analysis of over 30,000 genes identified the differential expression of 393 genes. Genes related to inflammation, cell adhesion, and transcription were validated with qPCR, and reduced expression was determined. Quantification of NF-kB phosphorylation served as a marker for the modulation of inflammation through gene transcription. Our results show that 4R was associated with a reduction in NFKB1 and ITGB5 gene expression, increased phosphorylation of NF-kB, and a decrease in macrophage adhesion in a blood-brain barrier model. These results indicate that 4R can partially modulate the peripheral immune response, making 4R a potential drug against post-ischemic inflammation.

Curcumin Prevents Neuroinflammation by Inducing Microglia to Transform into the M2-phenotype via CaMKKβ-dependent Activation of the AMP-Activated Protein Kinase Signal Pathway

2020 ◽  
Vol 17 (8) ◽  
pp. 735-752
Author(s):  
Peifeng Qiao ◽  
Jingxi Ma ◽  
Yangyang Wang ◽  
Zhenting Huang ◽  
Qian Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Ampk Activation ◽  
Ampk Signaling ◽  
M2 Polarization ◽  
Bv2 Cells ◽  
Anti Inflammatory ◽  
Amp Activated Protein Kinase ◽  
The Brain

Background: Neuroinflammation plays an important role in the pathophysiological process of various neurodegenerative diseases. It is well known that curcumin has obvious anti-inflammatory effects in various neuroinflammation models. However, its effect on the modulation of microglial polarization is largely unknown. Objective: This study aimed to investigate whether curcumin changed microglia to an anti-inflammatory M2-phenotype by activating the AMP-activated protein kinase (AMPK) signaling pathway. Methods: LPS treatment was used to establish BV2 cells and primary microglia neuroinflammation models. The neuroinflammation mouse model was established by an intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) in the lateral septal complex region of the brain. TNF-α was measured by ELISA, and cell viability was measured by Cell Counting Kit-8 (CCK-8). The expression of proinflammatory and anti-inflammatory cytokines was examined by Q-PCR and Western blot analysis. Phenotypic polarization of BV2 microglia was detected by immunofluorescence. Results: Curcumin enhanced AMPK activation in BV2 microglial cells in the presence and absence of LPS. Upon LPS stimulation, the addition of curcumin promoted M2 polarization of BV2 cells, as evidenced by suppressed M1 and the elevated M2 signature protein and gene expression. The effects of curcumin were inhibited by an AMPK inhibitor or AMPK knockdown. Calmodulin-dependent protein kinase kinase β (CaMKKβ) and liver kinase B1 (LKB1) are upstream kinases that activate AMPK. Curcumin can activate AMPK in Hela cells, which do not express LKB1. However, both the CaMKKβ inhibitor and siRNA blocked curcumin activation of AMPK in LPS-stimulated BV2 cells. Moreover, the CaMKKβ inhibitor and siRNA weaken the effect of curcumin suppression on M1 and enhancement of M2 protein and gene expression in LPS-stimulated BV2 cells. Finally, curcumin enhanced AMPK activation in the brain area where microglia were over-activated upon LPS stimulation in an in vivo neuroinflammation model. Moreover, curcumin also suppressed M1 and promoted M2 signature protein and gene expression in this in vivo model. Conclusion: Curcumin enhances microglia M2 polarization via the CaMKKβ-dependent AMPK signaling pathway. Additionally, curcumin treatment was found to be neuroprotective and thus might be considered as a novel therapeutic agent to treat the neurodegenerative disease such as Alzheimer‘s disease, Parkinson's disease, etc.

scholarly journals Myeloid cell and transcriptome signatures associated with inflammation resolution in a model of self-limiting acute brain inflammation

2018 ◽  
Author(s):  
Claire L Davies ◽  
Anirudh Patir ◽  
Barry W McColl
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Current Model ◽  
Gene Clusters ◽  
Brain Inflammation ◽  
Intracerebral Injection ◽  
Irreversible Damage ◽  
Inflammation Resolution ◽  
The Brain

AbstractInflammation contributes to tissue repair and restoration of function after infection or injury. However, some forms of inflammation can cause tissue damage and disease, particularly if inappropriately activated, excessive, or not resolved adequately. The mechanisms that prevent excessive or chronic inflammation are therefore important to understand. This is particularly important in the central nervous system where some effects of inflammation can have particularly harmful consequences, including irreversible damage. An increasing number of neurological disorders, both acute and chronic, and their complications are associated with aberrant neuroinflammatory activity.Here we describe a model of self-limiting acute brain inflammation optimised to study mechanisms underlying inflammation resolution. Inflammation was induced by intracerebral injection of lipopolysaccharide (LPS) and the temporal profile of key cellular and molecular changes were defined during the progression of the inflammatory response. The kinetics of accumulation and loss of neutrophils in the brain enabled well demarcated phases of inflammation to be operatively defined, including induction and resolution phases. Microglial reactivity and accumulation of monocyte-derived macrophages were maximal at the onset of and during the resolution phase. We profiled the transcriptome-wide gene expression changes at representative induction and resolution timepoints and used gene coexpression network analysis to identify gene clusters. This revealed a distinct cluster of genes associated with inflammation resolution that were induced selectively or maximally during this phase and indicated an active programming of gene expression that may drive resolution as has been described in other tissues. Induction of gene networks involved in lysosomal function, lipid metabolism and a comparative switch to MHC-II antigen presentation (relative to MHC-I during induction) were prominent during the resolution phase. The restoration and/or further induction of microglial homeostatic signature genes was notable during the resolution phase.We propose the current model as a tractable reductionist system to complement more complex models for further understanding how inflammation resolution in the brain is regulated and as a platform for in vivo testing/screening of candidate resolution-modifying interventions. Our data highlight how resolution involves active cellular and transcriptome reprogramming and identify candidate gene networks associated with resolution-phase adaptations that warrant further study.

1805-P: Insulin Regulates a Broad Network of Gene Expression in the Brain to Regulated Brain Metabolism and Neurotransmission

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1805-P
Author(s):  
WEIKANG CAI ◽  
THIAGO M. BATISTA ◽  
RUBEN GARCIA MARTIN ◽  
ALFRED RAMIREZ ◽  
MASAHIRO KONISHI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Metabolism ◽  
The Brain

Relative Expression of Mouse Udp-glucuronosyl Transferase 2b1 Gene in the Livers, Kidneys, and Hearts: The Influence of Nonsteroidal Anti-inflammatory Drug Treatment

2019 ◽  
Vol 20 (11) ◽  
pp. 918-923 ◽  
Author(s):  
Yazun Jarrar ◽  
Qais Jarrar ◽  
Mohammad Abu-Shalhoob ◽  
Abdulqader abed ◽  
Esra'a Sha'ban
Keyword(s):  
Gene Expression ◽  
Strongly Correlated ◽  
Chain Reaction ◽  
Inflammatory Drug ◽  
Relative Expression ◽  
Elimination Half ◽  
Endogenous Compounds ◽  
Polymerase Chain ◽  
Anti Inflammatory ◽  
Glucuronosyl Transferase

Background: Mouse Udp-glucuronosyl Transferase (UGT) 2b1 is equivalent to the human UGT2B7 enzyme, which is a phase II drug-metabolising enzyme and plays a major role in the metabolism of xenobiotic and endogenous compounds. This study aimed to find the relative expression of the mouse ugt2b1 gene in the liver, kidney, and heart organs and the influence of Nonsteroidal Anti-inflammatory Drug (NSAID) administration. Methods: Thirty-five Blab/c mice were divided into 5 groups and treated with different commonly-used NSAIDs; diclofenac, ibuprofen, meloxicam, and mefenamic acid for 14 days. The livers, kidneys, and hearts were isolated, while the expression of ugt2b1 gene was analysed with a quantitative real-time polymerase chain reaction technique. Results: It was found that the ugt2b1 gene is highly expressed in the liver, and then in the heart and the kidneys. NSAIDs significantly upregulated (ANOVA, p < 0.05) the expression of ugt2b1 in the heart, while they downregulated its expression (ANOVA, p < 0.05) in the liver and kidneys. The level of NSAIDs’ effect on ugt2b1 gene expression was strongly correlated (Spearman’s Rho correlation, p < 0.05) with NSAID’s lipophilicity in the liver and its elimination half-life in the heart. Conclusion: This study concluded that the mouse ugt2b1 gene was mainly expressed in the liver, as 14-day administration of different NSAIDs caused alterations in the expression of this gene, which may influence the metabolism of xenobiotic and endogenous compounds.

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