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Inflammasome microglia

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https://www.readbyqxmd.com/read/28830026/progesterone-therapy-induces-an-m1-to-m2-switch-in-microglia-phenotype-and-suppresses-nlrp3-inflammasome-in-a-cuprizone-induced-demyelination-mouse-model
#1
Roya Aryanpour, Parichehr Pasbakhsh, Kazem Zibara, Zeinab Namjoo, Fatemeh Beigi Boroujeni, Saeed Shahbeigi, Iraj Ragerdi Kashani, Cordian Beyer, Adib Zendehdel
Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice...
August 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28821266/endogenous-hydrogen-sulphide-attenuates-nlrp3-inflammasome-mediated-neuroinflammation-by-suppressing-the-p2x7-receptor-after-intracerebral-haemorrhage-in-rats
#2
Hengli Zhao, Pengyu Pan, Yang Yang, Hongfei Ge, Weixiang Chen, Jie Qu, Jiantao Shi, Gaoyu Cui, Xin Liu, Hua Feng, Yujie Chen
BACKGROUND: Emerging studies have demonstrated the important physiological and pathophysiological roles of hydrogen sulphide (H2S) as a gasotransmitter for NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-associated neuroinflammation in the central nervous system. However, the effects of H2S on neuroinflammation after intracerebral haemorrhage (ICH), especially on the NLRP3 inflammasome, remain unknown. METHODS: We employed a Sprague-Dawley rat of collagenase-induced ICH in the present study...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28798666/nlrp6-inflammasome-ameliorates-brain-injury-after-intracerebral-hemorrhage
#3
Peng-Fei Wang, Zhen-Guang Li, Yong Zhang, Xiao-Hua Ju, Xin-Wu Liu, Ai-Ming Zhou, Jing Chen
NLRP6 inflammasome, one of the important intracellular innate immune sensors, has been shown to regulate immune responses. However, its roles in the intracerebral hemorrhage (ICH) are completely not clear. In the present study, we investigated the expression profile and biological roles of NLRP6 inflammasome in perihematomal brain tissues of mice subjected to ICH. In this study, we investigated the expression profile of NLRP6 inflammasome in the perihematomal brain tissues and explored the biological role of NLRP6 inflammasome upon acute brain injury in mice subjected to ICH...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28655515/early-life-lipopolysaccharide-exposure-potentiates-forebrain-expression-of-nlrp3-inflammasome-proteins-and-anxiety-like-behavior-in-adolescent-rats
#4
Yuan Lei, Chu-Jun Chen, Xiao-Xin Yan, Zhiyuan Li, Xiao-Hua Deng
BACKGROUND: Neonatal inflammation may affect brain development and lead to cognitive and emotional deficits at adolescence and adulthood. The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is the core component of NLRP3 inflammasome, which may involve in neuroinflammation. We explored if early-life exposure to the bacterial endotoxin lipopolysaccharide (LPS) could promote the expression of proteins related to NLRP3 inflammasome, including NLRP3, the apoptosis-associated speck-like protein (ASC) and cysteiny aspartate-specific protease (Caspase-1) in the forebrain and behavioral alteration in adolescent rats...
June 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28630327/virus-induced-inflammasome-activation-is-suppressed-by-prostaglandin-d2-dp1-signaling
#5
Rahul Vijay, Anthony R Fehr, Ann M Janowski, Jeremiah Athmer, Dorthea L Wheeler, Matthew Grunewald, Ramakrishna Sompallae, Samarchith P Kurup, David K Meyerholz, Fayyaz S Sutterwala, Shuh Narumiya, Stanley Perlman
Prostaglandin D2 (PGD2), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD2 signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression analyses indicated that PGD2/DP1 signaling is required for up-regulation of a putative inflammasome inhibitor, PYDC3, in CD11b(+) cells in the CNS of infected mice...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#6
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28605578/roflupram-a-phosphodiesterase-4-inhibitior-suppresses-inflammasome-activation-through-autophagy-in-microglial-cells
#7
Tingting You, Yufang Cheng, Jiahong Zhong, Bingtian Bi, Bingqing Zeng, Wenhua Zheng, Haitao Wang, Jiangping Xu
Inhibition of phosphodiesterase 4 (PDE4) suppressed the inflammatory responses in the brain. However, the underlying mechanisms are poorly understood. Roflupram (ROF) is a novel PDE4 inhibitor. In the present study, we found that ROF enhanced the level of microtubule-associated protein 1 light chain 3 II (LC3-II) and decreased p62 in microglial BV-2 cells. Enhanced fluorescent signals were observed in BV-2 cells treated with ROF by Lysotracker red and acridine orange staining. In addition, immunofluorescence indicated a significant increase in punctate LC3...
August 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#8
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28595078/amyloidogenic-proteins-associated-with-neurodegenerative-diseases-activate-the-nlrp3-inflammasome
#9
REVIEW
Qian-Hang Shao, Xiao-Ling Zhang, Peng-Fei Yang, Yu-He Yuan, Nai-Hong Chen
Neuroinflammation has been shown as an essential factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and Multiple Sclerosis. Furthermore, activated microglia and increased pro-inflammatory cytokines are the major hallmarks in neurodegenerative diseases. A multimolecular complex named as inflammasome is involved in the process of inflammatory response, which can activate inflammatory caspases, leading to the cleavage and secretion of inflammatory cytokines, and finally generates a potent inflammatory response...
June 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28523794/mineralocorticoid-receptor-associates-with-pro-inflammatory-bias-in-hippocampus-of-spontaneously-hypertensive-rats
#10
María Elvira Brocca, Luciana Pietranera, Maria Meyer, Analia Lima, Paulina Roig, E Ronald de Kloet, Alejandro F De Nicola
Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry...
May 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28487495/naoling-decoction-restores-cognitive-function-by-inhibiting-the-neuroinflammatory-network-in-a-rat-model-of-alzheimer-s-disease
#11
Zian Xia, Weijun Peng, Shunhua Cheng, Bingwu Zhong, Chenxia Sheng, Chunhu Zhang, Wei Gong, Shuai Cheng, Jun Li, Zhe Wang
Neuroinflammation is central to the pathogenesis of Alzheimer's disease (AD). We previously showed that Naoling decoction (NLD), a traditional Chinese medicine, was effective against AD, acting by inhibiting expression of IL-1β and IL-6. In the present study, we generated the rat model of AD by injecting Aβ1-42 peptide intracerebroventricularly and evaluated the dose-dependent effects of NLD treatment. The NLD-treated rats exhibited significant improvements in cognitive function as evaluated by the Morris water maze test...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28486969/activation-of-p2x7-receptor-and-nlrp3-inflammasome-assembly-in-hippocampal-glial-cells-mediates-chronic-stress-induced-depressive-like-behaviors
#12
Na Yue, Huijie Huang, Xiaocang Zhu, Qiuqin Han, Yalin Wang, Bing Li, Qiong Liu, Gencheng Wu, Yuqiu Zhang, Jin Yu
BACKGROUND: In recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28486508/strong-upregulation-of-inflammatory-genes-accompanies-photoreceptor-demise-in-canine-models-of-retinal-degeneration
#13
Tatyana Appelbaum, Evelyn Santana, Gustavo D Aguirre
We have analyzed the complex pattern of the inflammatory response in early-onset canine models of human retinitis pigmentosa, rcd1, xlpra2 and erd, as well as late-onset xlpra1, in comparative manner. The time course of immune response genes and proteins expression was examined along the timeline of photoreceptors degeneration. Gene expression analysis of the early-onset models prior to and after the peak of photoreceptors death identified the involvement of multiple immune response genes including those encoding constituents of the NLRP3 inflammasome, its substrates, pro-IL1B, pro-IL18, and common components of IL1B, IL18 and TLR4 pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28438165/microglia-derived-il-1%C3%AE-promotes-chemokine-expression-by-m%C3%A3-ller-cells-and-rpe-in-focal-retinal-degeneration
#14
Riccardo Natoli, Nilisha Fernando, Michele Madigan, Joshua A Chu-Tan, Krisztina Valter, Jan Provis, Matt Rutar
BACKGROUND: Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we explore the role of interleukin-1β (IL-1β) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10 during photo-oxidative retinal damage, and the effect on both the accumulation of outer-retinal macrophages, and death of photoreceptors. METHODS: Inhibition of retinal IL-1β expression was performed using either siRNA or antibody neutralisation, which was intravitreally injected in SD rats prior to photo-oxidative damage...
April 24, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#15
Leslie Freeman, Haitao Guo, Clément N David, W June Brickey, Sushmita Jha, Jenny P-Y Ting
Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28401906/acrolein-acts-as-a-neurotoxin-in-the-nigrostriatal-dopaminergic-system-of-rat-involvement-of-%C3%AE-synuclein-aggregation-and-programmed-cell-death
#16
Yi-Ting Wang, Hui-Ching Lin, Wei-Zhong Zhao, Hui-Ju Huang, Yu-Li Lo, Hsiang-Tsui Wang, Anya Maan-Yuh Lin
Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28318352/the-role-of-nlrp3-casp1-in-inflammasome-mediated-neuroinflammation-and-autophagy-dysfunction-in-manganese-induced-hippocampal-dependent-impairment-of-learning-and-memory-ability
#17
Diya Wang, Jianbin Zhang, Wenkai Jiang, Zipeng Cao, Fang Zhao, Tongjian Cai, Michael Aschner, Wenjing Luo
Central nervous system (CNS) inflammation and autophagy dysfunction are known to be involved in the pathology of neurodegenerative diseases. Manganese (Mn), a neurotoxic metal, has the potential to induce microglia-mediated neuroinflammation as well as autophagy dysfunction. NLRP3 (NLR family, pyrin domain containing 3)- CASP1 (caspase 1) inflammasome-mediated neuroinflammation in microglia has specific relevance to neurological diseases. However, the mechanism driving these phenomena remains poorly understood...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#18
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28270571/hiv-1-tat-primes-and-activates-microglial-nlrp3-inflammasome-mediated-neuroinflammation
#19
Ernest T Chivero, Ming-Lei Guo, Palsamy Periyasamy, Ke Liao, Shannon E Callen, Shilpa Buch
Neuroinflammation associated with HIV-1 infection is a problem affecting ∼50% of HIV-infected individuals. NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in HIV-induced microglial activation, but the mechanism(s) remain unclear. Because HIV-1 Transactivator of Transcription (Tat) protein continues to be present despite antiretroviral therapy and activates NF-kB, we hypothesized that Tat could prime the NLRP3 inflammasome. We found a dose- and time-dependent induction of NLRP3 expression in microglia exposed to Tat compared with control...
March 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28255908/nlrp3-inflammasome-inhibitor-ameliorates-amyloid-pathology-in-a-mouse-model-of-alzheimer-s-disease
#20
Jun Yin, Fanpeng Zhao, Jeremy E Chojnacki, Jacob Fulp, William L Klein, Shijun Zhang, Xiongwei Zhu
The activation of the NLRP3 inflammasome signaling pathway plays an important role in the neuroinflammation in Alzheimer's disease (AD). In this study, we investigated the effects of JC-124, a rationally designed NLRP3 inflammasome inhibitor, on AD-related deficits in CRND8 APP transgenic mice (TgCRND8). We first demonstrated increased formation and activation of NLRP3 inflammasome in TgCRND8 mice compared to non-transgenic littermate controls, which was inhibited by the treatment with JC-124. Importantly, JC-124 treatment led to decreased levels of Aβ deposition and decreased levels of soluble and insoluble Aβ1-42 in the brain of CRND8 mice which was accompanied by reduced β-cleavage of APP, reduced activation of microglia but enhanced astrocytosis...
March 2, 2017: Molecular Neurobiology
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