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https://www.readbyqxmd.com/read/29471184/targeting-metabotropic-glutamate-receptors-for-the-treatment-of-neuroinflammation
#1
REVIEW
Francesco Fazio, Martina Ulivieri, Claudia Volpi, Marco Gargaro, Francesca Fallarino
A large body of evidence suggests that neuroinflammation lies at the core of nearly all CNS disorders, including psychiatric disorders. Invading and local immune cells orchestrate the series of events that lead to either tissue repair or damage in response to neuroinflammation. Both lymphocytes and microglia express metabotropic glutamate (mGlu) receptors, which respond to glutamate or other endogenous activators (e.g. some kynurenine metabolites of tryptophan metabolism) influencing immune phenotype and the balance between pro-inflammatory and anti-inflammatory cytokines...
February 19, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29471127/targeting-cd14-on-blood-derived-cells-improves-intracortical-microelectrode-performance
#2
Hillary W Bedell, John K Hermann, Madhumitha Ravikumar, Shushen Lin, Ashley Rein, Xujia Li, Emily Molinich, Patrick D Smith, Stephen M Selkirk, Robert H Miller, Steven Sidik, Dawn M Taylor, Jeffrey R Capadona
Intracortical microelectrodes afford researchers an effective tool to precisely monitor neural spiking activity. Additionally, intracortical microelectrodes have the ability to return function to individuals with paralysis as part of a brain computer interface. Unfortunately, the neural signals recorded by these electrodes degrade over time. Many strategies which target the biological and/or materials mediating failure modes of this decline of function are currently under investigation. The goal of this study is to identify a precise cellular target for future intervention to sustain chronic intracortical microelectrode performance...
February 13, 2018: Biomaterials
https://www.readbyqxmd.com/read/29471030/neuroprotective-effects-of-fecal-microbiota-transplantation-on-mptp-induced-parkinson-s-disease-mice-gut-microbiota-glial-reaction-and-tlr4-tnf-%C3%AE-signaling-pathway
#3
Meng-Fei Sun, Ying-Li Zhu, Zhi-Lan Zhou, Xue-Bing Jia, Yi-Da Xu, Qin Yang, Chun Cui, Yan-Qin Shen
Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs)...
February 19, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29468176/inhibition-of-the-potassium-channel-kv1-3-reduces-infarction-and-inflammation-in-ischemic-stroke
#4
Yi-Je Chen, Hai M Nguyen, Izumi Maezawa, Lee-Way Jin, Heike Wulff
Objective: Inhibitors of the voltage-gated K+ channel Kv1.3 are currently in development as immunomodulators for the treatment of autoimmune diseases. As Kv1.3 is also expressed on microglia and has been shown to be specifically up-regulated on "M1-like" microglia, we here tested the therapeutic hypothesis that the brain-penetrant small-molecule Kv1.3-inhibitor PAP-1 reduces secondary inflammatory damage after ischemia/reperfusion. Methods: We studied microglial Kv1...
February 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29467770/cytokines-stimulate-the-release-of-microvesicles-from-myeloid-cells-independently-from-the-p2x7-receptor-acid-sphingomyelinase-pathway
#5
Federico Colombo, Mattia Bastoni, Annamaria Nigro, Paola Podini, Annamaria Finardi, Giacomo Casella, Menon Ramesh, Cinthia Farina, Claudia Verderio, Roberto Furlan
Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we report that both pro- and anti-inflammatory cytokines, specifically interferon-γ and interleukin-4, are equally able to stimulate the production of MVs from microglia cells and monocytes. Additionally, we found this process to be independent from the best characterized molecular pathway so far described for membrane shedding, which is centered on the purinergic receptor P2X7, whose activation by high concentrations of extracellular ATP (exATP) results in membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29467608/understanding-the-role-of-adenosine-a2ar-heteroreceptor-complexes-in-neurodegeneration-and-neuroinflammation
#6
Dasiel O Borroto-Escuela, Sonja Hinz, Gemma Navarro, Rafael Franco, Christa E Müller, Kjell Fuxe
Adenosine is a nucleoside mainly formed by degradation of ATP, located intracellularly or extracellularly, and acts as a neuromodulator. It operates as a volume transmission signal through diffusion and flow in the extracellular space to modulate the activity of both glial cells and neurons. The effects of adenosine are mediated via four adenosine receptor subtypes: A1R, A2AR, A2BR, A3R. The A2AR has a wide-spread distribution but it is especially enriched in the ventral and dorsal striatum where it is mainly located in the striato-pallidal GABA neurons at a synaptic and extrasynaptic location...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29467001/neuregulin-1-elicits-a-regulatory-immune-response-following-traumatic-spinal-cord-injury
#7
Arsalan Alizadeh, Kallivalappil T Santhosh, Hardeep Kataria, Abdelilah S Gounni, Soheila Karimi-Abdolrezaee
BACKGROUND: Spinal cord injury (SCI) triggers a robust neuroinflammatory response that governs secondary injury mechanisms with both degenerative and pro-regenerative effects. Identifying new immunomodulatory therapies to promote the supportive aspect of immune response is critically needed for the treatment of SCI. We previously demonstrated that SCI results in acute and permanent depletion of the neuronally derived Neuregulin-1 (Nrg-1) in the spinal cord. Increasing the dysregulated level of Nrg-1 through acute intrathecal Nrg-1 treatment enhanced endogenous cell replacement and promoted white matter preservation and functional recovery in rat SCI...
February 21, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29467000/ginsenoside-re-protects-methamphetamine-induced-dopaminergic-neurotoxicity-in-mice-via-upregulation-of-dynorphin-mediated-%C3%AE%C2%BA-opioid-receptor-and-downregulation-of-substance-p-mediated-neurokinin-1-receptor
#8
Duy-Khanh Dang, Eun-Joo Shin, Dae-Joong Kim, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Jung Hwan Jeong, Jae Kyung Byun, Sung Kwon Ko, Guoying Bing, Jau-Shyong Hong, Hyoung-Chun Kim
BACKGROUND: We previously reported that ginsenoside Re (GRe) attenuated against methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant potentials. We also demonstrated that dynorphin possesses anti-inflammatory and antioxidant potentials against dopaminergic loss, and that balance between dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we examined whether GRe positively affects interactive modulation between dynorphin and substance P against MA neurotoxicity in mice...
February 21, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29466735/noninflammatory-changes-of-microglia-are-sufficient-to-cause-epilepsy
#9
Xiaofeng Zhao, Yuan Liao, Shannon Morgan, Ramkumar Mathur, Paul Feustel, Joseph Mazurkiewicz, Jiang Qian, Julia Chang, Gary W Mathern, Matthew A Adamo, Anthony L Ritaccio, Michael Gruenthal, Xinjun Zhu, Yunfei Huang
Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29466086/vulnerability-of-glia-and-vessels-of-rat-substantia-nigra-in-rotenone-parkinson-model
#10
Sanaa A M Elgayar, Amel A M Abdel-Hafez, Asmaa M S Gomaa, Raghda Elsherif
BACKGROUND: Astrocytes have been implicated as potentially exerting both neurotoxic and neuroprotective activities in Parkinson's disease (PD). Whether glial cells negatively impact the neuron integrity remains to be determined. We aimed to assess the vulnerability of glia and vessels in rat substantia nigra in a rotenone PD model. MATERIAL AND METHODS: Twenty adult male albino rats were divided into two equal groups: vehicle-control group (received dimethylsulfoxide + polyethylene glycol (PEG)-300, 1:1 v/v) and rotenone-treated group (received six doses of rotenone, 1...
March 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29465400/tumor-initiating-cells-induce-cxcr4-mediated-infiltration-of-pro-tumoral-macrophages-into-the-brain
#11
Kelda Chia, Julie Mazzolini, Marina Mione, Dirk Sieger
It is now clear that microglia and macrophages are present in brain tumors, but whether or how they affect initiation and development of tumors is not known. Exploiting the advantages of the zebrafish ( Danio rerio ) model, we showed that macrophages and microglia respond immediately upon oncogene activation in the brain. Overexpression of human AKT1 within neural cells of larval zebrafish led to a significant increase in the macrophage and microglia populations. By using a combination of transgenic and mutant zebrafish lines, we showed that this increase was caused by the infiltration of peripheral macrophages into the brain mediated via Sdf1b-Cxcr4b signaling...
February 21, 2018: ELife
https://www.readbyqxmd.com/read/29464573/intrinsic-inflammation-is-a-potential-anti-epileptogenic-target-in-the-organotypic-hippocampal-slice-model
#12
Seon-Ah Chong, Silvia Balosso, Catherine Vandenplas, Gregory Szczesny, Etienne Hanon, Kasper Claes, Xavier Van Damme, Bénédicte Danis, Jonathan Van Eyll, Christian Wolff, Annamaria Vezzani, Rafal M Kaminski, Isabelle Niespodziany
Understanding the mechanisms of epileptogenesis is essential to develop novel drugs that could prevent or modify the disease. Neuroinflammation has been proposed as a promising target for therapeutic interventions to inhibit the epileptogenic process that evolves from traumatic brain injury. However, it remains unclear whether cytokine-related pathways, particularly TNFα signaling, have a critical role in the development of epilepsy. In this study, we investigated the role of innate inflammation in an in vitro model of post-traumatic epileptogenesis...
February 20, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29463646/mutant-idh1-disrupts-pkm2-%C3%AE-catenin-brg1-transcriptional-network-driven-cd47-expression
#13
Pruthvi Gowda, Shruti Patrick, Ankita Singh, Touseef Sheikh, Ellora Sen
Gain-of-function mutation in isocitrate dehydrogenase1 (IDH1) affects immune-surveillance in gliomas. As elevated CD47 is associated with immune evasion in cancers, its status in gliomas harboring IDH1-MT was investigated. Decreased CD47 expression in IDH1-R132H overexpressing cells was accompanied by diminished nuclear β-catenin, PKM2 and TCF4 levels as compared to IDH1-WT. Inhibition of β-catenin in IDH1-WT abrogated CD47 expression, β-catenin-TCF4 interaction and transactivational activity of β-catenin/TCF4...
February 20, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29463176/neuroinflammation-after-traumatic-brain-injury-tbi-is-enhanced-in-activating-transcription-factor-3-atf3-mutant-mice
#14
Philip Foerstner, Rida Rehman, Sofia Anastasiadou, Melanie Haffner-Luntzer, Daniela Sinske, Anita Ignatius, Francesco Roselli, Bernd Knoell
Traumatic brain injury (TBI) induces a neuroinflammatory response resulting in astrocyte and microglia activation at the lesion site. This involves up-regulation of neuroinflammatory genes including chemokines and interleukins. However, so far there is lack of knowledge on transcription factors (TFs) modulating this TBI associated gene expression response. Herein we analyzed activating transcription factor 3 (ATF3), a TF encoding a regeneration-associated gene (RAG) predominantly studied in peripheral nervous system (PNS) injury...
February 20, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29463007/new-insights-into-the-role-of-neuron-specific-enolase-in-neuro-inflammation-neurodegeneration-and-neuroprotection
#15
REVIEW
Azizul Haque, Rachel Polcyn, Denise Matzelle, Naren L Banik
Neurodegeneration is a complex process that leads to irreversible neuronal damage and death in spinal cord injury (SCI) and various neurodegenerative diseases, which are serious, debilitating conditions. Despite exhaustive research, the cause of neuronal damage in these degenerative disorders is not completely understood. Elevation of cell surface α-enolase activates various inflammatory pathways, including the production of pro-inflammatory cytokines, chemokines, and some growth factors that are detrimental to neuronal cells...
February 18, 2018: Brain Sciences
https://www.readbyqxmd.com/read/29462849/synthetic-3-4-dihydroxyflavone-exerts-anti-neuroinflammatory-effects-in-bv2-microglia-and-a-mouse-model
#16
Namkwon Kim, Hyung-Seok Yoo, Yeon-Joo Ju, Myung Sook Oh, Kyung-Tae Lee, Kyung-Soo Inn, Nam-Jung Kim, Jong Kil Lee
Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model...
February 21, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29462698/piper-sarmentosum-roxb-confers-neuroprotection-on-beta-amyloid-a%C3%AE-induced-microglia-mediated-neuroinflammation-and-attenuates-tau-hyperphosphorylation-in-sh-sy5y-cells
#17
Emilia Tze Ying Yeo, Kelly Wang Ling Wong, Mun Ling See, Ka Yan Wong, Sook Yee Gan, Elaine Wan Ling Chan
ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aβ)-induced microglia-mediated neurotoxicity...
February 17, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29462012/neuroinflammation-and-central-sensitization-in-chronic-and-widespread-pain
#18
Ru-Rong Ji, Andrea Nackley, Yul Huh, Niccolò Terrando, William Maixner
Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness in central pain pathways after painful insults. Accumulating evidence suggests that central sensitization is also driven by neuroinflammation in the peripheral and central nervous system. A characteristic feature of neuroinflammation is the activation of glial cells, such as microglia and astrocytes, in the spinal cord and brain, leading to the release of proinflammatory cytokines and chemokines...
February 19, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29459868/characteristics-of-infection-immunity-regulated-by-toxoplasma-gondii-to-maintain-chronic-infection-in-the-brain
#19
Young Sang Hwang, Ji-Hun Shin, Jung-Pyo Yang, Bong-Kwang Jung, Sang Hyung Lee, Eun-Hee Shin
To examine the immune environment of chronic Toxoplasma gondii infection in the brain, the characteristics of infection-immunity (premunition) in infection with T . gondii strain ME49 were investigated for 12 weeks postinfection (PI). The results showed that neuronal cell death, microglia infiltration and activation, inflammatory and anti-inflammatory cytokine expression, Stat1 phosphorylation, and microglia activation and inflammatory gene transcripts related to M1 polarization in the brain were increased during the acute infection (AI) stage (within 6 weeks PI), suggesting that innate and cellular inflammatory response activation and neurodegeneration contributed to excessive inflammatory responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29458276/high-doses-of-minocycline-may-induce-delayed-activation-of-microglia-in-aged-rats-and-thus-cannot-prevent-postoperative-cognitive-dysfunction
#20
Wenyao Li, Qing Chai, Hongwei Zhang, Jing Ma, Chengfen Xu, Jifu Dong, Xianghua Wei, Zhiyi Wang, Kexian Zhang
Objective Postoperative cognitive dysfunction (POCD) is common after surgery in elderly patients and is associated with high morbidity. The molecular mechanisms responsible for POCD are unknown. Minocycline, an inhibitor of microglial activation, may be useful in treating and preventing POCD. We explored whether minocycline can inhibit microglial activation and prevent POCD in aged rats as a surgery model. Methods Rats aged 18 to 20 months were randomly allocated to the following groups: naïve, abdominal surgery alone, or minocycline injection before abdominal surgery...
January 1, 2018: Journal of International Medical Research
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