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https://www.readbyqxmd.com/read/29149212/mycolactone-displays-anti-inflammatory-effects-on-the-nervous-system
#1
Caroline Isaac, Annie Mauborgne, Alfonso Grimaldi, Kemy Ade, Michel Pohl, Cristina Limatola, Yves Boucher, Caroline Demangel, Laure Guenin-Macé
BACKGROUND: Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investigated whether mycolactone similarly affects the inflammatory responses of the nervous cell subsets involved in pain perception, transmission and maintenance. We also investigated the effects of mycolactone on the neuroinflammation that is associated with chronic pain in vivo...
November 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29133437/abnormal-microglia-and-enhanced-inflammation-related-gene-transcription-in-mice-with-conditional-deletion-of-ctcf-in-camk2a-cre-expressing-neurons
#2
Bryan E McGill, Ruteja A Barve, Susan E Maloney, Amy Strickland, Nicholas Rensing, Peter Wang, Michael Wong, Richard Head, David F Wozniak, Jeffrey Milbrandt
CCCTC-binding factor (CTCF) is an 11 zinc finger DNA-binding domain protein that regulates gene expression by modifying three dimensional chromatin structure. Human mutations in CTCF cause intellectual disability and autistic features. Knocking out Ctcf in mouse embryonic neurons is lethal by neonatal age, but the effects of CTCF deficiency in postnatal neurons are less well studied. We knocked out Ctcf postnatally in glutamatergic forebrain neurons under the control of Camk2a-CreCtcf(loxP/loxP) ;Camk2a-Cre+ (Ctcf CKO) mice of both sexes were viable and exhibited profound deficits in spatial learning/memory, impaired motor co-ordination, and decreased sociability by 4 months of age...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29131016/focal-transplantation-of-aberrant-glial-cells-carrying-the-sod1g93a-mutation-into-rat-spinal-cord-induces-extensive-gliosis
#3
Sofía Ibarburu, Emiliano Trias, Natalia Lago, Hugo Peluffo, Romina Barreto-Núñez, Valentina Varela, Joseph S Beckman, Luis Barbeito
OBJECTIVE: We aimed to determine the potential of aberrant glial cells (AbAs) isolated from the spinal cord of adult SOD1G93A symptomatic rats to induce gliosis and neuronal damage following focal transplantation into the lumbar spinal cord of wild-type rats. METHODS: AbAs were obtained from the spinal cords of SOD1G93A symptomatic rats. One hundred thousand cells were injected using a glass micropipette into the lumbar spinal cords (L3-L5) of syngeneic wild-type adult rats...
November 1, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29126430/lack-of-chronic-neuroinflammation-in-the-absence-of-focal-hemorrhage-in-a-rat-model-of-low-energy-blast-induced-tbi
#4
Miguel A Gama Sosa, Rita De Gasperi, Georgina S Perez Garcia, Heidi Sosa, Courtney Searcy, Danielle Vargas, Pierce L Janssen, Gissel M Perez, Anna E Tschiffely, William G Janssen, Richard M McCarron, Patrick R Hof, Fatemeh G Haghighi, Stephen T Ahlers, Gregory A Elder
Blast-related traumatic brain injury (TBI) has been a common cause of injury in the recent conflicts in Iraq and Afghanistan. Blast waves can damage blood vessels, neurons, and glial cells within the brain. Acutely, depending on the blast energy, blast wave duration, and number of exposures, blast waves disrupt the blood-brain barrier, triggering microglial activation and neuroinflammation. Recently, there has been much interest in the role that ongoing neuroinflammation may play in the chronic effects of TBI...
November 10, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29117434/co-culture-of-neurons-and-microglia
#5
Pamela J Roqué, Lucio G Costa
Microglia, the resident immune cells of the brain, have been implicated in numerous neurodegenerative and neurodevelopmental diseases. Activation of microglia by a variety of stimuli induces the release of factors, including pro- and anti-inflammatory cytokines and reactive oxygen species, that contribute to modulating neuro-inflammation and oxidative stress, two crucial processes linked to disorders of the central nervous system. The in vitro techniques described here will provide a set of protocols for the isolation and plating of primary cerebellar granule neurons, primary cortical microglia from a mixed glia culture, and methods for co-culturing both cell types...
November 8, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/29109020/an-immortalized-microglial-cell-line-mocha-derived-from-rat-cochlea
#6
G M Seigel, S Manohar, Y Y Bai, D Ding, R Salvi
Microglia are glial-immune cells that are essential for the function and survival of the central nervous system. Microglia not only protect neural tissues from immunological insults, but also play a critical role in neural development and repair. However, little is known about the biology of microglia in the cochlea, the auditory portion of the inner ear. In this study, we detected TMEM119+, CD11b+, CD45+ and Iba1+ populations of cells in the rat cochlea, particularly in Rosenthal's canal, inner sulcus and stria vascularis...
November 3, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29104495/exosomal-mir-7-mediates-bystander-autophagy-in-lung-after-focal-brain-irradiation-in-mice
#7
Shang Cai, Geng-Sheng Shi, Hui-Ying Cheng, Ya-Nan Zeng, Gen Li, Meng Zhang, Man Song, Ping-Kun Zhou, Ye Tian, Feng-Mei Cui, Qiu Chen
This study investigated whether exosomal microRNA-7 (miR-7) mediates lung bystander autophagy after focal brain irradiation in mice. After 10 Gy or sham irradiation of mice brains, lung tissues were extracted for the detection of autophagy markers by immunohistochemistry, western blotting, and quantitative real-time reverse transcription PCR (qRT-PCR), meanwhile the brains were dissociated, the neuron/astrocyte/microglia/oligodendrocyte were isolated, and the miR-7 expression in each population were detected, respectively...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29104062/stress-disinhibits-microglia-via-down-regulation-of-cd200r-a-mechanism-of-neuroinflammatory-priming
#8
Matthew G Frank, Laura K Fonken, Jessica L Annis, Linda R Watkins, Steven F Maier
Exposure to stressors primes the neuroinflammatory and microglial proinflammatory response to subsequent immune challenges, suggesting that stress might attenuate immunoregulatory mechanisms in the CNS microenvironment. CD200:CD200R is a key immunoregulatory signaling dyad that constrains microglial activation, and disruption of CD200:CD200R signaling primes microglia to subsequent immune challenges. Therefore, the present study examined the mediating role of CD200:CD200R signaling in stress-induced microglial priming...
November 2, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29101021/microglial-specific-transcriptome-changes-following-chronic-alcohol-consumption
#9
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer's disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis...
October 31, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29097315/mapping-of-thalamic-magnetic-susceptibility-in-multiple-sclerosis-indicates-decreasing-iron-with-disease-duration-a-proposed-mechanistic-relationship-between-inflammation-and-oligodendrocyte-vitality
#10
Ferdinand Schweser, Ana Luiza Raffaini Duarte Martins, Jesper Hagemeier, Fuchun Lin, Jannis Hanspach, Bianca Weinstock-Guttman, Simon Hametner, Niels P Bergsland, Michael G Dwyer, Robert Zivadinov
Recent advances in susceptibility MRI have dramatically improved the visualization of deep gray matter brain regions and the quantification of their magnetic properties in vivo, providing a novel tool to study the poorly understood iron homeostasis in the human brain. In this study, we used an advanced combination of the recent quantitative susceptibility mapping technique with dedicated analysis methods to study intra-thalamic tissue alterations in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS)...
October 30, 2017: NeuroImage
https://www.readbyqxmd.com/read/29081811/transplanted-adult-neural-stem-cells-express-sonic-hedgehog-in-vivo-and-suppress-white-matter-neuroinflammation-after-experimental-traumatic-brain-injury
#11
Genevieve M Sullivan, Regina C Armstrong
Neural stem cells (NSCs) delivered intraventricularly may be therapeutic for diffuse white matter pathology after traumatic brain injury (TBI). To test this concept, NSCs isolated from adult mouse subventricular zone (SVZ) were transplanted into the lateral ventricle of adult mice at two weeks post-TBI followed by analysis at four weeks post-TBI. We examined sonic hedgehog (Shh) signaling as a candidate mechanism by which transplanted NSCs may regulate neuroregeneration and/or neuroinflammation responses of endogenous cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29067585/intrinsic-response-towards-physiologic-stiffness-is-cell-type-dependent
#12
Michael Reimer, Silviya Petrova Zustiak, Saahil Sheth, Joseph Martin Schober
In the continuous search for better tissue engineering scaffolds it has become increasingly clear that the substrate properties dramatically affect cell responses. Here we compared cells from a physiologically stiff tissue, melanoma, to cells isolated from a physiologically soft tissue, brain. We measured the cell line responses to laminin immobilized onto glass or polyacrylamide hydrogels tuned to have a Young's modulus ranging from 1 to 390 kPa. Single cells were analyzed for spreading area, shape, total actin content, actin-based morphological features and modification of immobilized laminin...
October 24, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29046463/flow-cytometric-detection-of-prp-sc-in-neurons-and-glial-cells-from-prion-infected-mouse-brains
#13
Takeshi Yamasaki, Akio Suzuki, Rie Hasebe, Motohiro Horiuchi
In prion diseases, an abnormal isoform of prion protein (PrP(Sc)) accumulates in neurons, astrocytes, and microglia in the brains of animals affected with prions. Detailed analyses of PrP(Sc)-positive neurons and glial cells are required to clarify their pathophysiological roles in the disease. Here we report a novel method for the detection of PrP(Sc) in neurons and glial cells from the brains of prion-infected mice by flow cytometry using PrP(Sc)-specific staining with mAb 132. The combination of PrP(Sc) staining and immunolabeling of neural cell markers clearly distinguished neurons, astrocytes, and microglia that were positive for PrP(Sc) from those that were PrP(Sc) negative...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29043065/cns-cell-type-localization-and-lps-response-of-tlr-signaling-pathways
#14
Gizelle M McCarthy, Courtney R Bridges, Yuri A Blednov, R Adron Harris
Background: Innate immune signaling in the brain has emerged as a contributor to many central nervous system (CNS) pathologies, including mood disorders, neurodegenerative disorders, neurodevelopmental disorders, and addiction. Toll-like receptors (TLRs), a key component of the innate immune response, are particularly implicated in neuroimmune dysfunction. However, most of our understanding about TLR signaling comes from the peripheral immune response, and it is becoming clear that the CNS immune response is unique...
2017: F1000Research
https://www.readbyqxmd.com/read/29041969/glial-cells-are-functionally-impaired-in-juvenile-neuronal-ceroid-lipofuscinosis-and-detrimental-to-neurons
#15
Lotta Parviainen, Sybille Dihanich, Greg W Anderson, Andrew M Wong, Helen R Brooks, Rosella Abeti, Payam Rezaie, Giovanna Lalli, Simon Pope, Simon J Heales, Hannah M Mitchison, Brenda P Williams, Jonathan D Cooper
The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed...
October 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29034506/microglial-induced-m%C3%A3-ller-cell-gliosis-is-attenuated-by-progesterone-in-a-mouse-model-of-retinitis-pigmentosa
#16
Sarah L Roche, Ana M Ruiz-Lopez, Jennifer N Moloney, Ashleigh M Byrne, Thomas G Cotter
Norgestrel, a progesterone analogue, has demonstrated neuroprotective effects in a mouse model of retinitis pigmentosa. Neuroprotection is achieved in part through Norgestrels anti-inflammatory properties, alleviating detrimental microglial activity. Gliosis is a feature of many neurodegenerative diseases of the retina, including retinitis pigmentosa. Müller glia, a type of macroglia found in the retina, are major contributors of gliosis, characterized by the upregulation of glial fibrillary acidic protein (GFAP)...
October 16, 2017: Glia
https://www.readbyqxmd.com/read/29024033/impact-of-x-irradiation-on-microglia
#17
Franziska Menzel, Nicole Kaiser, Susann Haehnel, Felicitas Rapp, Ina Patties, Nina Schöneberg, Zhana Haimon, Kerstin Immig, Ingo Bechmann
Irradiation is widely used to treat brain tumors, and also to create bone marrow (BM) chimeras. BM chimeras are widely used to dissect functions and origin of microglia and blood-derived mononuclear cells under homeostatic or pathological conditions. This is facilitated by the fact that microglia survive irradiation and are thus regarded radio-resistant. In this study, we tested whether microglia are indeed radio-resistant and looked for potential mechanisms that might explain this phenomenon. We analyzed the radio-resistance of microglia independently of their physiological brain environment compared to other mononuclear cells from spleen and brain after X-irradiation with 7 Gy or 30 Gy...
January 2018: Glia
https://www.readbyqxmd.com/read/29020624/temporal-tracking-of-microglia-activation-in-neurodegeneration-at-single-cell-resolution
#18
Hansruedi Mathys, Chinnakkaruppan Adaikkan, Fan Gao, Jennie Z Young, Elodie Manet, Martin Hemberg, Philip L De Jager, Richard M Ransohoff, Aviv Regev, Li-Huei Tsai
Microglia, the tissue-resident macrophages in the brain, are damage sensors that react to nearly any perturbation, including neurodegenerative diseases such as Alzheimer's disease (AD). Here, using single-cell RNA sequencing, we determined the transcriptome of more than 1,600 individual microglia cells isolated from the hippocampus of a mouse model of severe neurodegeneration with AD-like phenotypes and of control mice at multiple time points during progression of neurodegeneration. In this neurodegeneration model, we discovered two molecularly distinct reactive microglia phenotypes that are typified by modules of co-regulated type I and type II interferon response genes, respectively...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28991528/protosappanin-a-exerts-anti-neuroinflammatory-effect-by-inhibiting-jak2-stat3-pathway-in-lipopolysaccharide-induced-bv2-microglia
#19
Li-Chao Wang, Li-Xi Liao, Ming-Bo Zhao, Xin Dong, Ke-Wu Zeng, Peng-Fei Tu
Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer's disease and Parkinson's disease. Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders. Protosappanin A (PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L.. In this work, the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored. Results showed that PTA significantly inhibited the production of TNF-α and IL-1β in LPS-activated BV2 microglia...
September 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28972143/shedding-of-membrane-associated-ldl-receptor-related-protein-1-from-microglia-amplifies-and-sustains-neuroinflammation
#20
Coralie Brifault, Andrew S Gilder, Emilia Laudati, Michael Banki, Steven L Gonias
In the CNS, microglia are activated in response to injury or infection and in neurodegenerative diseases. The endocytic and cell signaling receptor, LDL receptor-related protein-1 (LRP1), is reported to suppress innate immunity in macrophages and oppose microglial activation. The goal of this study was to identify novel mechanisms by which LRP1 may regulate microglial activation. Using primary cultures of microglia isolated from mouse brains, we demonstrated that LRP1 gene silencing increases expression of proinflammatory mediators; however, the observed response was modest...
November 10, 2017: Journal of Biological Chemistry
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