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https://www.readbyqxmd.com/read/28319103/microglia-activation-due-to-obesity-programs-metabolic-failure-leading-to-type-two-diabetes
#1
REVIEW
R Maldonado-Ruiz, L Montalvo-Martínez, L Fuentes-Mera, A Camacho
Obesity is an energy metabolism disorder that increases susceptibility to the development of metabolic diseases. Recently, it has been described that obese subjects have a phenotype of chronic inflammation in organs that are metabolically relevant for glucose homeostasis and energy. Altered expression of immune system molecules such as interleukins IL-1, IL-6, IL-18, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), and plasminogen activator inhibitor-1 (PAI-1), among others, has been associated with the development of chronic inflammation in obesity...
March 20, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28296539/high-salt-induced-activation-and-expression-of-inflammatory-cytokines-in-cultured-astrocytes
#2
Zhezhi Deng, Yuge Wang, Li Zhou, Yilong Shan, Sha Tan, Wei Cai, Siyuan Liao, Lisheng Peng, Zhengqi Lu
Salt (sodium chloride, NaCl) accumulation in the brain is associated with various diseases of central nervous system (CNS). Activation of astrocytes is an important manifestation of pathophysiological processes in the CNS. However, the direct impact of high salt (HS) environment on astrocytes is unclear. In the current study, we found that high salt treatment can induce activation of astrocytes both in vivo and in vitro, manifested as morphological alteration coupled with increased expression of glial fibrillary acidic protein (GFAP)...
March 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28293439/proteomic-analysis-of-hdac3-selective-inhibitor-in-the-regulation-of-inflammatory-response-of-primary-microglia
#3
Mingxu Xia, Qiuchen Zhao, He Zhang, Yanting Chen, Zengqiang Yuan, Yun Xu, Meijuan Zhang
HDAC3 has been shown to regulate inflammation. However, the role of HDAC3 in primary microglia is largely unknown. RGFP966 is a newly discovered selective HDAC3 inhibitor. In this study, we used protein mass spectrometry to analyze protein alterations in LPS-treated primary microglia with the application of RGFP966. Generally, about 2000 proteins were studied. 168 of 444 (37.8%) LPS-induced proteins were significantly reduced with the treatment of RGFP966, which mainly concentrated on Toll-like receptor signaling pathway...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28264445/equol-a-dietary-daidzein-gut-metabolite-attenuates-microglial-activation-and-potentiates-neuroprotection-in-vitro
#4
Lalita Subedi, Eunhee Ji, Dongyun Shin, Jongsik Jin, Joo Hong Yeo, Sun Yeou Kim
Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max) as primary isoflavones, possess anti-inflammatory activity, but the effect of its active metabolite Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) has not been well established. In this study, we investigated the anti-neuroinflammatory and neuroprotective effect of Equol in vitro. To evaluate the potential effects of Equol, three major types of central nervous system (CNS) cells, including microglia (BV-2), astrocytes (C6), and neurons (N2a), were used...
February 27, 2017: Nutrients
https://www.readbyqxmd.com/read/28245546/luteolin-inhibits-fibrillary-%C3%AE-amyloid1-40-induced-inflammation-in-a-human-blood-brain-barrier-model-by-suppressing-the-p38-mapk-mediated-nf-%C3%AE%C2%BAb-signaling-pathways
#5
Jun-Xia Zhang, Jian-Guo Xing, Lin-Lin Wang, Hai-Lun Jiang, Shui-Long Guo, Rui Liu
Amyloid-β peptides (Aβ) exist in several forms and are known as key modulators of Alzheimer's disease (AD). Fibrillary Aβ (fAβ) has been found to disrupt the blood-brain barrier (BBB) by triggering and promoting inflammation. In this study, luteolin, a naturally occurring flavonoid that has shown beneficial properties in the central nervous system, was evaluated as a potential agent to preserve barrier function and inhibit inflammatory responses at the BBB that was injured by fAβ1-40. We established an in vitro BBB model by co-culturing human brain microvascular endothelial cells (hBMECs) and human astrocytes (hAs) under fAβ1-40-damaged conditions and investigated the effect of luteolin by analyzing cellular toxicity, barrier function, cytokine production and inflammation-related intracellular signaling pathways...
February 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#6
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28164283/monocytes-microglia-and-cd200-cd200r1-signaling-are-essential-in-the-transmission-of-inflammation-from-the-periphery-to-the-central-nervous-system
#7
Xin Xie, Xiaoguang Luo, Na Liu, Xiaohong Li, Fan Lou, Yumin Zheng, Yan Ren
Peripheral inflammation is known to trigger neuroinflammation and neurodegenerative disease. However, the key components during the propagation of inflammation from the periphery to the central nervous system (CNS) remain unclear. Lipopolysaccharide (LPS) was administered to Sprague-Dawley rats to induce peripheral inflammation. An intravenous injection and an intranigral injection of clodronate liposomes (CL) were given to deplete monocytes and microglia, respectively. Recombinant CD200 fusion protein (CD200Fc) or an anti-CD200R1 antibody was injected into the substantia nigra (SN) to manipulate the involvement of CD200 and CD200R1...
February 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28112393/psoriasin-has-divergent-effects-on-the-innate-immune-responses-of-murine-glial-cells
#8
Sandra Jansen, Eugenia Kress, Athanassios Fragoulis, Christoph J Wruck, Ronald Wolf, Joachim Grötzinger, Matthias Michalek, Thomas Pufe, Simone C Tauber, Lars-Ove Brandenburg
Antimicrobial peptides are an important part of the innate immune defense in the central nervous system (CNS). The expression of the antimicrobial peptides psoriasin (S100A7) is up-regulated during bacterial meningitis. However, the exact mechanisms induced by psoriasin to modulate glial cell activity are not yet fully understood. Our hypothesis is that psoriasin induced pro- and anti-inflammatory signaling pathways as well as regenerative factors to contribute in total to a balanced immune response. Therefore, we used psoriasin-stimulated glial cells and analyzed the translocation of the pro-inflammatory transcription factor nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) in murine glial cells and the expression of pro- and anti-inflammatory mediators by real time RT-PCR, ELISA technique, and western blotting...
January 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28112182/hippocampal-cyslt1r-knockdown-or-blockade-represses-lps-induced-depressive-behaviors-and-neuroinflammatory-response-in-mice
#9
Jing-Ran Lin, Shun-Chang Fang, Su-Su Tang, Mei Hu, Yan Long, Arijit Ghosh, Hong-Bin Sun, Ling-Yi Kong, Hao Hong
Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLT1R) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLT1R in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLT1R knockdown and CysLT1R blockade on LPS-induced depressive-like behavior in mice. We found that injection of LPS (0...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28057080/combination-of-alpha-synuclein-immunotherapy-with-anti-inflammatory-treatment-in-a-transgenic-mouse-model-of-multiple-system-atrophy
#10
Elvira Valera, Brian Spencer, Jerel A Fields, Ivy Trinh, Anthony Adame, Michael Mante, Edward Rockenstein, Paula Desplats, Eliezer Masliah
Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by the pathological accumulation of alpha-synuclein (α-syn) in oligodendrocytes. Therapeutic efforts to stop or delay the progression of MSA have yielded suboptimal results in clinical trials, and there are no efficient treatments currently available for MSA patients. We hypothesize that combining therapies targeting different aspects of the disease may lead to better clinical outcomes. To test this hypothesis, we combined the use of a single-chain antibody targeting α-syn modified for improved central nervous system penetration (CD5-D5) with an unconventional anti-inflammatory treatment (lenalidomide) in the myelin basic protein (MBP)-α-syn transgenic mouse model of MSA...
January 5, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28052249/opposing-functions-of-microglial-and-macrophagic-tnfr2-in-the-pathogenesis-of-experimental-autoimmune-encephalomyelitis
#11
Han Gao, Matt C Danzi, Claire S Choi, Mehran Taherian, Camilla Dalby-Hansen, Ditte G Ellman, Pernille M Madsen, John L Bixby, Vance P Lemmon, Kate L Lambertsen, Roberta Brambilla
In multiple sclerosis (MS), soluble tumor necrosis factor (TNF) is detrimental via activation of TNF receptor 1 (TNFR1), whereas transmembrane TNF is beneficial primarily by activating TNF receptor 2 (TNFR2). Here, we investigate the role of TNFR2 in microglia and monocytes/macrophages in experimental autoimmune encephalomyelitis (EAE), a model of MS, by cell-specific gene targeting. We show that TNFR2 ablation in microglia leads to early onset of EAE with increased leukocyte infiltration, T cell activation, and demyelination in the central nervous system (CNS)...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28028734/galectin-1-reduces-neuroinflammation-via-modulation-of-nitric-oxide-arginase-signaling-in-hiv-1-transfected-microglia-a-gold-nanoparticle-galectin-1-nanoplex-a-possible-neurotherapeutic
#12
Ravikumar Aalinkeel, Courtney S Mangum, Eliane Abou-Jaoude, Jessica L Reynolds, Maixian Liu, Karin Sundquist, Neil U Parikh, Lee D Chaves, Manoj J Mammen, Stanley A Schwartz, Supriya D Mahajan
Galectins are a family of β-galactoside-binding lectins that are important modulators of homeostasis in the central nervous system (CNS). Galectin-1 is a pivotal regulator of microglia activation that alters the immune balance from neurodegeneration to neuroprotection and could have therapeutic relevance in HIV associated neurocognitive disorders (HAND). We have previously shown that galectin-1 treatment decreased oxidative stress in microglia and hypothesize that the mechanism underlying this phenomenon is the cross regulatory interactions between Nitric oxide (NO) and Arginase I activity in microglia...
December 27, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28011263/prenatal-alcohol-exposure-potentiates-chronic-neuropathic-pain-spinal-glial-and-immune-cell-activation-and-alters-sciatic-nerve-and-drg-cytokine-levels
#13
Shahani Noor, Joshua J Sanchez, Arden G Vanderwall, Melody S Sun, Jessie R Maxwell, Suzy Davies, Lauren L Jantzie, Timothy R Petersen, Daniel D Savage, Erin D Milligan
A growing body of evidence indicates that prenatal alcohol exposure (PAE) may predispose individuals to secondary medical disabilities later in life. Animal models of PAE reveal neuroimmune sequelae such as elevated brain astrocyte and microglial activation with corresponding region-specific changes in immune signaling molecules such as cytokines and chemokines. The aim of this study was to evaluate the effects of moderate PAE on the development and maintenance of allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in adult male rat offspring...
March 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27927222/tollip-an-early-regulator-of-the-acute-inflammatory-response-in-the-substantia-nigra
#14
Marie Humbert-Claude, D Duc, D Dwir, L Thieren, J Sandström von Tobel, C Begka, F Legueux, D Velin, M H Maillard, K Q Do, F Monnet-Tschudi, L Tenenbaum
BACKGROUND: Tollip is a ubiquitously expressed protein, originally described as a modulator of the IL-1R/TLR-NF-κB signaling pathways. Although this property has been well characterized in peripheral cells, and despite some evidence of its expression in the central nervous system, the role of Tollip in neuroinflammation remains poorly understood. The present study sought to explore the implication of Tollip in inflammation in the substantia nigra pars compacta, the structure affected in Parkinson's disease...
December 7, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27915186/role-of-the-purinergic-signaling-in-epilepsy
#15
REVIEW
Marek Cieślak, Andrzej Wojtczak, Michał Komoszyński
Adenine nucleotides and adenosine are signaling molecules that activate purinergic receptors P1 and P2. Activation of A1 adenosine receptors has an anticonvulsant action, whereas activation of A2A receptors might initiate seizures. Therefore, a significant limitation to the use of A1 receptor agonists as drugs in the CNS might be their peripheral side effects. The anti-epileptic activity of adenosine is related to its increased concentration outside the cell. This increase might result from the inhibition of the equilibrative nucleoside transporters (ENTs)...
February 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27862694/mesenchymal-stem-cell-derived-microvesicles-modulate-lipopolysaccharides-induced-inflammatory-responses-to-microglia-cells
#16
Yarúa Jaimes, Yahaira Naaldijk, Kerstin Wenk, Christiane Leovsky, Frank Emmrich
Microglia cells are the central nervous system immune cells and have been pointed out as the main mediators of the inflammation leading to neurodegenerative disorders. Mesenchymal stromal cells (MSCs) are a heterogeneous population of cells with very high self-renewal properties and uncomplicated in vitro culture. Research has shown that MSCs have the capacity to induce tissue regeneration and reduce inflammation. Studies demonstrated that MSCs have complex paracrine machineries involving shedding of cell-derived microvesicles (MVs), which entail part of the regulatory and regenerative activity of MSCs, as observed in animal models...
March 2017: Stem Cells
https://www.readbyqxmd.com/read/27814300/role-of-suppressor-of-cytokine-signaling-3-socs3-in-altering-activated-microglia-phenotype-in-appswe-ps1de9-mice
#17
Naotoshi Iwahara, Shin Hisahara, Jun Kawamata, Akihiro Matsumura, Kazuki Yokokawa, Taro Saito, Mai Fujikura, Tatsuo Manabe, Hiromi Suzuki, Takashi Matsushita, Syuuichirou Suzuki, Shun Shimohama
In response to changes of the central nervous system environment, microglia are capable of acquiring diverse phenotypes for cytotoxic or immune regulation and resolution of injury. Alzheimer's disease (AD) pathology also induces several microglial activations, resulting in production of pro-inflammatory cytokines and reactive oxygen species or clearance of amyloid-β (Aβ) through phagocytosis. We previously demonstrated that microglial activation and increase in oxidative stress started from the middle age in APPswe/PS1dE9 mice, and hypothesized that M1 activation occurs in middle-aged AD mice by Aβ stimulation...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27791020/essential-protective-role-of-tumor-necrosis-factor-receptor-2-in-neurodegeneration
#18
Yun Dong, Roman Fischer, Petrus J W Naudé, Olaf Maier, Csaba Nyakas, Maëlle Duffey, Eddy A Van der Zee, Doortje Dekens, Wanda Douwenga, Andreas Herrmann, Eric Guenzi, Roland E Kontermann, Klaus Pfizenmaier, Ulrich L M Eisel
Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNFR2, an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27760889/g-aminobutyric-acid-promotes-methionine-choline-deficient-diet-induced-nonalcoholic-steatohepatitis
#19
Seok Roh Yoon, Cho Ara, Zhou Zixiong, Jeong Hyuneui, Park Jeong-Eun, Cha Youn-Soo, Oh Suk-Heung, Lim Chae-Woong, Kim Bumseok
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27685630/pharmacologic-inhibition-of-reactive-gliosis-blocks-tnf-%C3%AE-mediated-neuronal-apoptosis
#20
Izhar Livne-Bar, Susy Lam, Darren Chan, Xiaoxin Guo, Idil Askar, Adrian Nahirnyj, John G Flanagan, Jeremy M Sivak
Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and increased polymerization of type III intermediate filaments (IFs), particularly glial fibrillary acidic protein and vimentin. However, the consequences of IF dynamics in the adult CNS remains unclear, and no pharmacologic tools have been available to target this mechanism in vivo...
September 29, 2016: Cell Death & Disease
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