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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
#1
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/28552674/enrichment-increases-hippocampal-neurogenesis-independent-of-blood-monocyte-derived-microglia-presence-following-high-dose-total-body-irradiation
#2
Marc J Ruitenberg, Julia Wells, Perry F Bartlett, Alan R Harvey, Jana Vukovic
Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to at least 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche...
May 24, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28459434/mice-deficient-in-nrros-show-abnormal-microglial-development-and-neurological-disorders
#3
Kit Wong, Rajkumar Noubade, Paolo Manzanillo, Naruhisa Ota, Oded Foreman, Jason A Hackney, Brad A Friedman, Rajita Pappu, Kimberly Scearce-Levie, Wenjun Ouyang
Microglia and other tissue-resident macrophages within the central nervous system (CNS) have essential roles in neural development, inflammation and homeostasis. However, the molecular pathways underlying their development and function remain poorly understood. Here we report that mice deficient in NRROS, a myeloid-expressed transmembrane protein in the endoplasmic reticulum, develop spontaneous neurological disorders. NRROS-deficient (Nrros(-/-)) mice show defects in motor functions and die before 6 months of age...
June 2017: Nature Immunology
https://www.readbyqxmd.com/read/28389721/chemokines-in-neuron-glial-cell-interaction-and-pathogenesis-of-neuropathic-pain
#4
REVIEW
Zhi-Jun Zhang, Bao-Chun Jiang, Yong-Jing Gao
Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system...
April 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28388927/exposure-to-gestational-diabetes-mellitus-induces-neuroinflammation-derangement-of-hippocampal-neurons-and-cognitive-changes-in-rat-offspring
#5
Billy Vuong, Gary Odero, Stephanie Rozbacher, Mackenzie Stevenson, Stephanie M Kereliuk, Troy J Pereira, Vernon W Dolinsky, Tiina M Kauppinen
BACKGROUND: Birth cohort studies link gestational diabetes mellitus (GDM) with impaired cognitive performance in the offspring. However, the mechanisms involved are unknown. We tested the hypothesis that obesity-associated GDM induces chronic neuroinflammation and disturbs the development of neuronal circuitry resulting in impaired cognitive abilities in the offspring. METHODS: In rats, GDM was induced by feeding dams a diet high in sucrose and fatty acids. Brains of neonatal (E20) and young adult (15-week-old) offspring of GDM and lean dams were analyzed by immunohistochemistry, cytokine assay, and western blotting...
April 7, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28343297/association-of-the-cx3cr1-v249i-variant-with-neurofibrillary-pathology-progression-in-late-onset-alzheimer-s-disease
#6
Alan López-López, Ellen Gelpi, Diana Maria Lopategui, Jose M Vidal-Taboada
Neuroinflammation and microglial dysfunction have a prominent role in the pathogenesis of late-onset Alzheimer's disease (LOAD). CX3CR1 is a microglia-specific gene involved in microglia-neuron crosstalk and neuroinflammation. Numerous evidence show the involvement of CX3CR1 in AD. The aim of this study was to investigate if some functional genetic variants of this gene could influence on LOAD's outcome, in a neuropathologically confirmed Spanish cohort. We designed an open, pragmatic, case-control retrospective study including a total of 475 subjects (205 pathologically confirmed AD cases and 270 controls)...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28342179/common-polymorphisms-of-cx3cr1-gene-modify-als-outcome-a-population-based-study
#7
Andrea Calvo, Cristina Moglia, Antonio Canosa, Stefania Cammarosano, Antonio Ilardi, Davide Bertuzzo, Bryan J Traynor, Maura Brunetti, Marco Barberis, Gabriele Mora, Federico Casale, Adriano Chiò
INTRODUCTION: In the brain the CX3CR1 gene is only expressed by microglia where it acts as a key mediator of the neuron-microglia interactions. We assessed whether the two common polymorphisms of the CX3CR1 gene (V249I and T280M) modify amyotrophic lateral sclerosis (ALS) phenotype. METHODS: The study included 755 ALS patients diagnosed in Piemonte between 2007 and 2012 and 369 age- and gender-matched controls, all genotyped using the same chips. RESULTS: Neither of the variants were associated with an increased risk of ALS...
March 25, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28320442/analysis-of-monocyte-infiltration-in-mptp-mice-reveals-that-microglial-cx3cr1-protects-against-neurotoxic-over-induction-of-monocyte-attracting-ccl2-by-astrocytes
#8
Vincent R Parillaud, Guillaume Lornet, Yann Monnet, Anne-Laure Privat, Andrei T Haddad, Vanessa Brochard, Amaury Bekaert, Camille Baudesson de Chanville, Etienne C Hirsch, Christophe Combadière, Stéphane Hunot, Christian S Lobsiger
BACKGROUND: Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2(+) monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death...
March 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28264978/deletion-of-the-fractalkine-receptor-cx3cr1-improves-endogenous-repair-axon-sprouting-and-synaptogenesis-after-spinal-cord-injury-in-mice
#9
Camila M Freria, Jodie C E Hall, Ping Wei, Zhen Guan, Dana M McTigue, Phillip G Popovich
Impaired signaling via CX3CR1, the fractalkine receptor, promotes recovery after traumatic spinal contusion injury in mice, a benefit achieved in part by reducing macrophage-mediated injury at the lesion epicenter. Here, we tested the hypothesis that CX3CR1-dependent changes in microglia and macrophage functions also will enhance neuroplasticity, at and several segments below the injury epicenter. New data show that in the presence of inflammatory stimuli, CX3CR1-deficient (CX3CR1(-/-)) microglia and macrophages adopt a reparative phenotype and increase expression of genes that encode neurotrophic and gliogenic proteins...
March 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28264694/cell-specific-deletion-of-c1qa-identifies-microglia-as-the-dominant-source-of-c1q-in-mouse-brain
#10
Maria I Fonseca, Shu-Hui Chu, Michael X Hernandez, Melody J Fang, Lila Modarresi, Pooja Selvan, Grant R MacGregor, Andrea J Tenner
BACKGROUND: The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain. METHODS: To identify the source(s) of C1q in the brain, the C1qa gene was selectively inactivated in the microglia or Thy-1(+) neurons in both wild type mice and a mouse model of Alzheimer's disease (AD), and C1q synthesis assessed by immunohistochemistry, QPCR, and western blot analysis...
March 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28216676/fractalkine-cx3cr1-signaling-is-critical-for-progesterone-mediated-neuroprotection-in-the-retina
#11
Sarah L Roche, Alice C Wyse-Jackson, Ana M Ruiz-Lopez, Ashleigh M Byrne, Thomas G Cotter
Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP, that rd10 microglia drive degeneration of viable neurons. Norgestrel, a progesterone analogue, primes viable neurons against potential microglial damage. In the current study we wished to investigate this neuroprotective effect further. We were particularly interested in the role of fractalkine-CX3CR1 signaling, previously shown to mediate photoreceptor-microglia crosstalk and promote survival in the rd10 retina...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153531/a-selective-cb2r-agonist-jwh133-restores-neuronal-circuit-after-germinal-matrix-hemorrhage-in-the-preterm-via-cx3cr1-microglia
#12
Jun Tang, Hongping Miao, Bing Jiang, Qianwei Chen, Liang Tan, Yihao Tao, Jianbo Zhang, Fabao Gao, Hua Feng, Gang Zhu, Zhi Chen
Microglia play dual roles after germinal matrix hemorrhage, and the neurotrophic phenotype maybe neuroprotective. However, the phenotype transformation and the way by which neuron-microglia dialogue remain unclear. We raise the hypothesis that a cannabinoid receptor2 agonist (JWH133) accelerates the CX3CR1(+) microglia secreting neurotrophic factors and restores damaged neuronal circuit. Here, we report a novel function of JWH133 in transforming the microglia CX3CR1 positive that secrete brain-derived neurotrophic factor (BDNF), which triggers neuron proliferation and neuronal restoration...
June 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28101527/regulation-of-physical-microglia-neuron-interactions-by-fractalkine-signaling-after-status-epilepticus
#13
Ukpong B Eyo, Jiyun Peng, Madhuvika Murugan, Mingshu Mo, Almin Lalani, Ping Xie, Pingyi Xu, David J Margolis, Long-Jun Wu
Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28088249/interactions-of-human-microglia-cells-with-japanese-encephalitis-virus
#14
Nils Lannes, Viviane Neuhaus, Brigitte Scolari, Solange Kharoubi-Hess, Michael Walch, Artur Summerfield, Luis Filgueira
BACKGROUND: Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans. Severe Japanese encephalitis cases display strong inflammatory responses in the central nervous system and an accumulation of viral particles in specific brain regions. Microglia cells are the unique brain-resident immune cell population with potent migratory functions and have been proposed to act as a viral reservoir for JEV. Animal models suggest that the targeting of microglia by JEV is partially responsible for inflammatory reactions in the brain...
January 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#15
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
June 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27932942/loss-of-fractalkine-signaling-exacerbates-axon-transport-dysfunction-in-a-chronic-model-of-glaucoma
#16
Kevin T Breen, Sarah R Anderson, Michael R Steele, David J Calkins, Alejandra Bosco, Monica L Vetter
Neurodegeneration in glaucoma results in decline and loss of retinal ganglion cells (RGCs), and is associated with activation of myeloid cells such as microglia and macrophages. The chemokine fractalkine (FKN or Cx3cl1) mediates communication from neurons to myeloid cells. Signaling through its receptor Cx3cr1 has been implicated in multiple neurodegenerative diseases, but the effects on neuronal pathology are variable. Since it is unknown how FKN-mediated crosstalk influences RGC degeneration in glaucoma, we assessed this in a chronic mouse model, DBA/2J...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27890560/the-hippocampal-transcriptomic-signature-of-stress-resilience-in-mice-with-microglial-fractalkine-receptor-cx3cr1-deficiency
#17
Neta Rimmerman, Nofar Schottlender, Ronen Reshef, Nadav Dan-Goor, Raz Yirmiya
Clinical studies suggest that key genetic factors involved in stress resilience are related to the innate immune system. In the brain, this system includes microglia cells, which play a major role in stress responsiveness. Consistently, mice with deletion of the CX3CR1 gene (CX3CR1(-/-) mice), which in the brain is expressed exclusively by microglia, exhibit resilience to chronic stress. Here, we compared the emotional, cognitive, neurogenic and microglial responses to chronic unpredictable stress (CUS) between CX3CR1(-/-) and wild type (WT) mice...
November 23, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27814376/progesterone-attenuates-microglial-driven-retinal-degeneration-and-stimulates-protective-fractalkine-cx3cr1-signaling
#18
Sarah L Roche, Alice C Wyse-Jackson, Violeta Gómez-Vicente, Pedro Lax, Ana M Ruiz-Lopez, Ashleigh M Byrne, Nicolás Cuenca, Thomas G Cotter
Retinitis pigmentosa (RP) is a degenerative disease leading to photoreceptor cell loss. Mouse models of RP, such as the rd10 mouse (B6.CXBl-Pde6brd10/J), have enhanced our understanding of the disease, allowing for development of potential therapeutics. In 2011, our group first demonstrated that the synthetic progesterone analogue 'Norgestrel' is neuroprotective in two mouse models of retinal degeneration, including the rd10 mouse. We have since elucidated several mechanisms by which Norgestrel protects stressed photoreceptors, such as upregulating growth factors...
2016: PloS One
https://www.readbyqxmd.com/read/27697456/prenatal-infection-leads-to-asd-like-behavior-and-altered-synaptic-pruning-in-the-mouse-offspring
#19
Lourdes Fernández de Cossío, Andrea Guzmán, Suzanne van der Veldt, Giamal N Luheshi
Environmental challenges to the maternal immune system during pregnancy have been associated with an increase in the frequency of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) appearing in the offspring. Microglia, the brain's resident immune-cells, are now known to be critically involved in normal brain development, shaping connections between neurons by pruning superfluous synaptic spines. Our aim was to investigate whether maternal infection during critical stages of gestation compromises the role of microglia in sculpting neuronal circuits...
September 30, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27687148/cathepsin-s-contributes-to-microglia-mediated-olfactory-dysfunction-through-the-regulation-of-cx3cl1-cx3cr1-axis-in-a-niemann-pick-disease-type-c1-model
#20
Yoojin Seo, Hyung-Sik Kim, Insung Kang, Soon Won Choi, Tae-Hoon Shin, Ji-Hee Shin, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Myung Geun Kook, Kyung-Sun Kang
Microglia can aggravate olfactory dysfunction by mediating neuronal death in the olfactory bulb (OB) of a murine model of Niemann-Pick disease type C1 (NPC1), a fatal neurodegenerative disorder accompanied by lipid trafficking defects. In this study, we focused on the crosstalk between neurons and microglia to elucidate the mechanisms underlying extensive microgliosis in the NPC1-affected brain. Microglia in the OB of NPC1 mice strongly expressed CX3C chemokine receptor 1 (Cx3cr1), a specific receptor for the neural chemokine C-X3-C motif ligand 1 (Cx3cl1)...
December 2016: Glia
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