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Microglia activation

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https://www.readbyqxmd.com/read/29676181/identification-of-glia-phenotype-modulators-based-on-select-glial-function-regulatory-signaling-pathways
#1
Sun-Hwa Lee, Kyoungho Suk
Despite the considerable social and economic burden on the healthcare system worldwide due to neurodegenerative diseases, there are currently few disease-altering treatment options for many of these conditions. Therefore, new approaches for both prevention and intervention for neurodegenerative diseases are urgently required. Microglia-mediated neurotoxicity is one of the pathologic hallmarks common to Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Current therapeutic approaches to target microglia-mediated neurotoxicity are focused on the identification of glia phenotype modulators (GPMs), which can inhibit the 'classical' pro-inflammatory and neurotoxic phenotypes of microglia...
April 20, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29675728/histone-deacetylase-2-inhibitor-cay10683-alleviates-lipopolysaccharide-induced-neuroinflammation-through-attenuating-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#2
Fang-Zhou Jiao, Yao Wang, Hai-Yue Zhang, Wen-Bin Zhang, Lu-Wen Wang, Zuo-Jiong Gong
Neuroinflammation involves in the progression of many central nervous system diseases. Several studies have shown that histone deacetylase (HDAC) inhibitors modulated inflammatory responses in lipopolysaccharide (LPS) stimulated microglia. While, the mechanism is still unclear. The aim of present study was to investigate the effect of HDAC2 inhibitor CAY10683 on inflammatory responses and TLR4/NF-κB signaling pathways in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. The effect of CAY10683 on cell viability of BV2 microglial cells was detected by CCK-8 assay...
April 19, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29674955/the-communication-between-the-immune-and-nervous-systems-the-role-of-il-1%C3%AE-in-synaptopathies
#3
REVIEW
Davide Pozzi, Elisabetta Menna, Alice Canzi, Genni Desiato, Cristina Mantovani, Michela Matteoli
In the last 15 years, groundbreaking genetic progress has underlined a convergence onto coherent synaptic pathways for most psychiatric and neurodevelopmental disorders, which are now collectively called "synaptopathies." However, the modest size of inheritance detected so far indicates a multifactorial etiology for these disorders, underlining the key contribution of environmental effects to them. Inflammation is known to influence the risk and/or severity of a variety of synaptopathies. In particular, pro-inflammatory cytokines, produced and released in the brain by activated astrocytes and microglia, may play a pivotal role in these pathologies...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29674348/rkip-mediates-autoimmune-inflammation-by-positively-regulating-il-17r-signaling
#4
Wenlong Lin, Ning Wang, Kangxing Zhou, Fasheng Su, Yu Jiang, Jianan Shou, Huan Liu, Chunmei Ma, Youchun Qian, Kai Wang, Xiaojian Wang
Th17 cells contribute to the development of autoimmune diseases by secreting interleukin-17 (IL-17), which activates its receptor (IL-17R) that is expressed on epithelial cells, macrophages, microglia, and resident neuroectodermal cells. However, the mechanisms through which IL-17R-mediated signaling contributes to the development of autoimmune disease have not been completely elucidated. Here, we demonstrate that Raf-1 kinase inhibitor protein (RKIP) deficiency in mice ameliorates the symptoms of experimental autoimmune encephalomyelitis (EAE)...
April 19, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29673913/epothilone-d-inhibits-microglia-mediated-spread-of-alpha-synuclein-aggregates
#5
Dario Valdinocci, Gary Grant, Tracey Dickson, Dean L Pountney
Multiple System Atrophy (MSA) is a progressive neurodegenerative disease characterized by chronic neuroinflammation and widespread α-synuclein (α-syn) cytoplasmic inclusions. Neuroinflammation associated with microglial cells is typically located in brain regions with α-syn deposits. The potential link between microglial cell migration and the transport of pathological α-syn protein in MSA was investigated. Qualitative analysis via immunofluorescence of MSA cases (n = 4) revealed microglial cells bearing α-syn inclusions distal from oligodendrocytes bearing α-syn cytoplasmic inclusions, as well as close interactions between microglia and oligodendrocytes bearing α-syn, suggestive of a potential transfer mechanism between microglia and α-syn bearing cells in MSA and the possibility of microglia acting as a mobile vehicle to spread α-syn between anatomically connected brain regions...
April 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29673550/complex-role-of-chemokine-mediators-in-animal-models-of-alzheimer-s-disease
#6
REVIEW
Elodie Martin, Cécile Delarasse
Chemokines are a family of cytokines, first described to play a role in the immune system. However, neurons and glial cells also express chemokines and their receptors. In the central nervous system, chemokines are involved in several neural functions, in particular in the control of cell communications and neuronal activity. In pathological conditions, chemokines participate in neuroinflammatory and neurodegenerative processes. In Alzheimer's disease (AD), chemokines play a role in the development of the two main lesions, amyloid β plaques and neurofibrillary tangles...
February 2018: Biomedical Journal
https://www.readbyqxmd.com/read/29672844/longitudinal-positron-emission-tomography-imaging-of-glial-cell-activation-in-a-mouse-model-of-mesial-temporal-lobe-epilepsy-toward-identification-of-optimal-treatment-windows
#7
Duc-Loc Nguyen, Catriona Wimberley, Charles Truillet, Benoit Jego, Fabien Caillé, Géraldine Pottier, Raphaël Boisgard, Irène Buvat, Viviane Bouilleret
OBJECTIVE: Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process...
April 19, 2018: Epilepsia
https://www.readbyqxmd.com/read/29670526/taraxasterol-inhibits-lps-induced-inflammatory-response-in-bv2-microglia-cells-by-activating-lxr%C3%AE
#8
Bin Liu, Zhaoqi He, Jingjing Wang, Zhuoyuan Xin, Jiaxin Wang, Fan Li, Yunhe Fu
Neuroinflammation plays a critical role in the development of neurodegenerative diseases. Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale , has been reported to have anti-inflammatory effect. The aim of this study was to investigate the anti-inflammatory effects and mechanism of taraxasterol in LPS-stimulated BV2 microglia cells. BV2 microglia cells were treated with taraxasterol 12 h before LPS stimulation. The effects of taraxasterol on LPS-induced TNF-α and IL-1β production were detected by ELISA...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29670465/emerging-roles-of-immune-cells-in-postoperative-cognitive-dysfunction
#9
REVIEW
Yue Liu, Yiqing Yin
Postoperative cognitive dysfunction (POCD), a long-lasting cognitive decline after surgery, is currently a major clinical problem with no clear pathophysiological mechanism or effective therapy. Accumulating evidence suggests that neuroinflammation plays a critical role in POCD. After surgery, alarmins are leaked from the injury sites and proinflammatory cytokines are increased in the peripheral circulation. Neurons in the hippocampus, which is responsible for learning and memory, can be damaged by cytokines transmitted to the brain parenchyma...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29669946/pravastatin-therapy-during-preeclampsia-prevents-long-term-adverse-health-effects-in-mice
#10
Nicola Garrett, Joaquim Pombo, Michelle Umpierrez, James E Clark, Mark Simmons, Guillermina Girardi
Preeclampsia (PE), associates with long-term increased risk for cardiovascular disease in women, suggesting that PE is not an isolated disease of pregnancy. It is not known if increased risk for long-term diseases is due to PE-specific factors or to prepregnancy renal and cardiovascular risk factors. We used a mouse model in which a WT female with normal prepregnancy health develops PE to investigate if preeclampsia causes long-term cardiovascular consequences after pregnancy for mothers and offspring. Mothers exhibited endothelial dysfunction and hypertension after PE and had glomerular injury that not only persisted but deteriorated, leading to fibrosis...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29668503/tetrahydroxystilbene-glycoside-antagonizes-%C3%AE-amyloid-induced-inflammatory-injury-in-microglia-cells-by-regulating-pu-1-expression
#11
Chenli Jiao, Feng Gao, Li Ou, Jinhua Yu, Min Li, Peifeng Wei, Feng Miu
Inhibiting β-amyloid (Aβ)-induced microglial activation is proposed as an effective strategy for the treatment of Alzheimer's disease. Tetrahydroxystilbene glycoside (TSG) is the main active ingredient of Polygonum multiflorum and has a wide range of biological properties, including antiinflammation. Here, we focused on the function and regulatory mechanism of TSG in Aβ-induced N9 and BV2 cells. The results showed that Aβ treatment induced the activation of microglia cells and the production of inflammatory molecules, including inducible nitric oxide synthase, nitric oxide, cyclooxygenase 2, and prostaglandin E2, which were significantly inhibited by TSG pretreatment...
April 17, 2018: Neuroreport
https://www.readbyqxmd.com/read/29668471/evaluation-of-the-role-of-abcb1gene-polymorphic-variants-on-psychiatric-disorders-predisposition-in-macedonian-population
#12
Zorica Naumovska, Aleksandra K Nestorovska, Zoran Sterjev, Ana Filipce, Aleksandra Grozdanova, Aleksandar Dimovski, Ljubica Suturkova, Vladimir Serafimoski
The psychiatric and other CNS disorders are characterized with unregulated neuro-inflammatory processes and chronic microglia cell activation resulting with detrimental effect. ABCB1gene polymorphismsC1236T, G2677T/Aand C3435T are associated with P-glycoprotein expression and function andare linked with predisposition to psychiatric disorders such as schizophrenia and bipolar disorders. The relationship between mood disorders and glucocorticoids has been confirmed and ABCB1 SNPs influence the glucocorticoids access to the brain...
December 1, 2017: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/29667931/ave0991-a-nonpeptide-analogue-of-ang-1-7-attenuates-aging-related-neuroinflammation
#13
Teng Jiang, Liu-Jun Xue, Yang Yang, Qing-Guang Wang, Xiao Xue, Zhou Ou, Qing Gao, Jian-Quan Shi, Liang Wu, Ying-Dong Zhang
During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7)...
April 17, 2018: Aging
https://www.readbyqxmd.com/read/29667667/%C3%AE-cyperone-inhibits-lps-induced-inflammation-in-bv-2-cells-through-activation-of-akt-nrf2-ho-1-and-suppression-of-the-nf-%C3%AE%C2%BAb-pathway
#14
Bingxu Huang, Dewei He, Guangxin Chen, Xin Ran, Wenjin Guo, Xingchi Kan, Wei Wang, Dianfeng Liu, Shoupeng Fu, Juxiong Liu
Accumulating evidence has shown that activated microglia cause inflammatory immune response, which could lead to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. α-Cyperone, one of the main ingredients of Cyperus rotundus oil, has been reported to possess anti-inflammatory activity in activated macrophages. In this study, we found that α-cyperone markedly decreased the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-induced BV-2 cells...
April 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29666700/oil-palm-phenolics-inhibit-the-in-vitro-aggregation-of-%C3%AE-amyloid-peptide-into-oligomeric-complexes
#15
Robert P Weinberg, Vera V Koledova, Hyeari Shin, Jennifer H Park, Yew Ai Tan, Anthony J Sinskey, Ravigadevi Sambanthamurthi, ChoKyun Rha
Alzheimer's disease is a severe neurodegenerative disease characterized by the aggregation of amyloid- β peptide (A β ) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of A β 42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that A β 42 aggregation is inhibited in vitro by oil palm phenolics (OPP), an aqueous extract from the oil palm tree (Elaeis guineensis) ...
2018: International Journal of Alzheimer's Disease
https://www.readbyqxmd.com/read/29666569/inhibitory-effects-of-betulinic-acid-on-lps-induced-neuroinflammation-involve-m2-microglial-polarization-via-camkk%C3%AE-dependent-ampk-activation
#16
Chuwen Li, Chao Zhang, Hefeng Zhou, Yu Feng, Fan Tang, Maggie P M Hoi, Chengwei He, Dan Ma, Chao Zhao, Simon M Y Lee
In response to the microenvironment, microglia may polarize into either an M1 pro-inflammatory phenotype, exacerbating neurotoxicity, or an M2 anti-inflammatory phenotype, conferring neuroprotection. Betulinic acid (BA) is a naturally pentacyclic triterpenoid with considerable anti-inflammatory properties. Here, we aim to investigate the potential effects of BA on microglial phenotype polarization and to reveal the underlying mechanisms of action. First, we confirmed that BA promoted M2 polarization and inhibited M1 polarization in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29666475/lincrna-cox2-regulates-nlrp3-inflammasome-and-autophagy-mediated-neuroinflammation
#17
Zhenyi Xue, Zimu Zhang, Hongkun Liu, Wen Li, Xiangdong Guo, Zhihui Zhang, Ying Liu, Long Jia, Yan Li, Yinghui Ren, Hongwei Yang, Lijuan Zhang, Qi Zhang, Yurong Da, Junwei Hao, Zhi Yao, Rongxin Zhang
Inflammasome activation plays key roles in host defense, but also contributes to the pathogenesis of auto-inflammatory, and neurodegenerative diseases. As autophagy is connected with both the innate and adaptive immune systems, autophagic dysfunction is also closely related to inflammation, infection, and neurodegeneration. Here we identify that lincRNA-Cox2, previously known as a mediator of both the activation and repression of immune genes expression in innate immune cells, could bind NF-κB p65 and promote its nuclear translocation and transcription, modulating the expression of inflammasome sensor NLRP3 and adaptor ASC...
April 17, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29665726/dexmedetomidine-mitigates-microglia-mediated-neuroinflammation-through-up-regulation-of-programmed-cell-death-protein-1-in-a-rat-spinal-cord-injury-model
#18
Hefan He, Yingying Zhou, Yilin Zhou, Jiayuan Zhuang, Xu He, Siyuan Wang, Wenping Lin
Excessive neuroinflammation aggravates neurological damage after spinal cord injury (SCI). Controlling neuroinflammation might favor neuroregeneration and tissue repair. Dexmedetomidine is reported to inhibit post-SCI neuroinflammation in previous research. In the current study, to determine the mechanisms by which dexmedetomidine inhibits neuroinflammation, we tested the effect of dexmedetomidine hydrochloride on microglia in vitro and in a rat SCI model. We found that dexmedetomidine hydrochloride up-regulated programmed cell death protein 1 (PD-1), an immunoregulatory molecule, in activated microglia but not in resting microglia...
April 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29665116/atrophy-and-microglial-distribution-in-primary-progressive-aphasia-with-tdp-43
#19
Garam Kim, Kabriya Bolbolan, Tamar Gefen, Sandra Weintraub, Eileen H Bigio, Emily Rogalski, Marek-Marsel Mesulam, Changiz Geula
OBJECTIVE: To quantitatively determine the density and distribution of activated microglia across cortical regions and hemispheres in the brains of primary progressive aphasia (PPA) participants with pathologic diagnoses of FTLD-TDP, and to examine the relationships between microglial densities, patterns of focal atrophy, TDP-43 inclusions, and clinical phenotype. METHODS: Activated microglia and TDP-43 inclusions were visualized in whole-hemisphere brain sections using immunohistochemical methods from 5 participants with PPA-TDP...
April 17, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29665074/parkin-deficiency-modulates-nlrp3-inflammasome-activation-by-attenuating-an-a20-dependent-negative-feedback-loop
#20
François Mouton-Liger, Thibault Rosazza, Julia Sepulveda-Diaz, Amélie Ieang, Sidi-Mohamed Hassoun, Emilie Claire, Graziella Mangone, Alexis Brice, Patrick P Michel, Jean-Christophe Corvol, Olga Corti
Neuroinflammation and mitochondrial dysfunction, key mechanisms in the pathogenesis of Parkinson's disease (PD), are usually explored independently. Loss-of-function mutations of PARK2 and PARK6, encoding the E3 ubiquitin protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1, account for a large proportion of cases of autosomal recessive early-onset PD. PINK1 and Parkin regulate mitochondrial quality control and have been linked to the modulation of innate immunity pathways. We report here an exacerbation of NLRP3 inflammasome activation by specific inducers in microglia and bone marrow-derived macrophages from Park2-/- and Pink1-/- mice...
April 17, 2018: Glia
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