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https://www.readbyqxmd.com/read/29769333/microglia-are-critical-in-host-defense-against-prion-disease
#1
James A Carroll, Brent Race, Katie Williams, James Striebel, Bruce Chesebro
Microglial cells in the central nervous system play important roles in neurodevelopment and resistance to infection, yet microglia can become neurotoxic under some conditions. An early event during prion infection is the activation of microglia and astrocytes in the brain prior to damage or death of neurons. Previous prion disease studies using two different strategies to manipulate signaling through the microglial receptor CSF-1R reported contrary effects on survival from prion disease. However, in these studies, reduction of microglial numbers and function were variable, thus confounding interpretation of the results...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29740932/antagonizing-peroxisome-proliferator-activated-receptor-%C3%AE-facilitates-m1-to-m2-shift-of-microglia-by-enhancing-autophagy-via-the-lkb1-ampk-signaling-pathway
#2
Juan Ji, Teng-Fei Xue, Xu-Dong Guo, Jin Yang, Ruo-Bing Guo, Juan Wang, Ji-Ye Huang, Xiao-Jie Zhao, Xiu-Lan Sun
Microglia-mediated neuroinflammation plays a dual role in various brain diseases due to distinct microglial phenotypes, including deleterious M1 and neuroprotective M2. There is growing evidence that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone prevents lipopolysaccharide (LPS)-induced microglial activation. Here, we observed that antagonizing PPARγ promoted LPS-stimulated changes in polarization from the M1 to the M2 phenotype in primary microglia. PPARγ antagonist T0070907 increased the expression of M2 markers, including CD206, IL-4, IGF-1, TGF-β1, TGF-β2, TGF-β3, G-CSF, and GM-CSF, and reduced the expression of M1 markers, such as CD86, Cox-2, iNOS, IL-1β, IL-6, TNF-α, IFN-γ, and CCL2, thereby inhibiting NFκB-IKKβ activation...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29670611/advances-in-biomarker-guided-therapy-for-pediatric-and-adult-onset-neuroinflammatory-disorders-targeting-chemokines-cytokines
#3
REVIEW
Michael R Pranzatelli
The concept and recognized components of "neuroinflammation" are expanding at the intersection of neurobiology and immunobiology. Chemokines (CKs), no longer merely necessary for immune cell trafficking and positioning, have multiple physiologic, developmental, and modulatory functionalities in the central nervous system (CNS) through neuron-glia interactions and other mechanisms affecting neurotransmission. They issue the "help me" cry of neurons and astrocytes in response to CNS injury, engaging invading lymphoid cells (T cells and B cells) and myeloid cells (dendritic cells, monocytes, and neutrophils) (adaptive immunity), as well as microglia and macrophages (innate immunity), in a cascade of events, some beneficial (reparative), others destructive (excitotoxic)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29579271/interleukin-34-is-present-at-the-fetal-maternal-interface-and-induces-immunoregulatory-macrophages-of-a-decidual-phenotype-in-vitro
#4
R Lindau, R B Mehta, G E Lash, G Papapavlou, R Boij, G Berg, M C Jenmalm, J Ernerudh, J Svensson-Arvelund
STUDY QUESTION: Is the newly discovered cytokine interleukin (IL)-34 expressed at the human fetal-maternal interface in order to influence polarization of monocytes into macrophages of a decidual immunoregulatory phenotype? SUMMARY ANSWER: IL-34 was found to be present at the fetal-maternal interface, in both fetal placenta and maternal decidua, and it was able to polarize monocytes into macrophages of a decidual phenotype. WHAT IS KNOWN ALREADY: IL-34 was shown to bind to the same receptor as macrophage-colony stimulating factor (M-CSF), which has an important immunomodulatory role at the fetal-maternal interface, for example by polarizing decidual macrophages to an M2-like regulatory phenotype...
April 1, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29574097/dynamic-changes-in-hippocampal-microglia-contribute-to-depressive-like-behavior-induced-by-early-social-isolation
#5
Yu Gong, Lijuan Tong, Rongrong Yang, Wenfeng Hu, Xingguo Xu, Wenjing Wang, Peng Wang, Xu Lu, Minhui Gao, Yue Wu, Xing Xu, Yaru Zhang, Zhuo Chen, Chao Huang
Depression triggered by early-life stress has begun to attract wide attention due to its severe symptoms and poor treatment outcomes. However, the pathophysiological mechanism for this type of depression remains unclear. Recently, we and others reported that different types of chronic stress induce a significant loss of hippocampal microglia, which is mediated by an initial activation of these microglia. Since early-life stress also promotes microglial activation, we investigated the dynamic changes in hippocampal microglia in mice suffering from depression induced by early social isolation (ESI)...
March 21, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29554978/peroxiredoxin-2-activates-microglia-by-interacting-with-toll-like-receptor-4-after-subarachnoid-hemorrhage
#6
Yue Lu, Xiang-Sheng Zhang, Zi-Huan Zhang, Xiao-Ming Zhou, Yong-Yue Gao, Guang-Jie Liu, Han Wang, Ling-Yun Wu, Wei Li, Chun-Hua Hang
BACKGROUND: Peroxiredoxin (Prx) protein family have been reported as important damage-associated molecular patterns (DAMPs) in ischemic stroke. Since peroxiredoxin 2 (Prx2) is the third most abundant protein in erythrocytes and the second most protein in the cerebrospinal fluid in traumatic brain injury and subarachnoid hemorrhage (SAH) patients, we assessed the role of extracellular Prx2 in the context of SAH. METHODS: We introduced a co-culture system of primary neurons and microglia...
March 19, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29522854/chronic-amyloid-%C3%AE-oligomer-infusion-evokes-sustained-inflammation-and-microglial-changes-in-the-rat-hippocampus-via-nlrp3
#7
Csaba Fekete, Csaba Vastagh, Ádám Dénes, Erik Hrabovszky, Gábor Nyiri, Imre Kalló, Zsolt Liposits, Miklós Sárvári
Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβOs), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks...
March 6, 2018: Neuroscience
https://www.readbyqxmd.com/read/29467770/cytokines-stimulate-the-release-of-microvesicles-from-myeloid-cells-independently-from-the-p2x7-receptor-acid-sphingomyelinase-pathway
#8
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/29448957/brain-region-specific-enhancement-of-remyelination-and-prevention-of-demyelination-by-the-csf1r-kinase-inhibitor-blz945
#9
Nicolau Beckmann, Elisa Giorgetti, Anna Neuhaus, Stefan Zurbruegg, Nathalie Accart, Paul Smith, Julien Perdoux, Ludovic Perrot, Mark Nash, Sandrine Desrayaud, Peter Wipfli, Wilfried Frieauff, Derya R Shimshek
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack the scope of promoting CNS repair, in particular remyelination. Microglia play a pivotal role in regulating myelination processes, and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for microglia differentiation and survival. Here, we investigated the effects of the CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes in the 5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance imaging (MRI) and histology...
February 15, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29425372/sleep-deprivation-and-csf-biomarkers-for-alzheimer-disease
#10
Martin Olsson, Johan Ärlig, Jan Hedner, Kaj Blennow, Henrik Zetterberg
Study Objective: To investigate the cumulative effect of 5 consecutive nights of partial sleep deprivation on a panel of cerebrospinal fluid (CSF) biomarkers in healthy adults. Methods: A randomized, cross-over study conducted at the University of Gothenburg. The participants (N=13) were healthy adults (20-40 years of age) with a normal sleeping pattern. The participants underwent a baseline sleep period consisting of 5 nights with 8h spent in bed. A subsequent period with partial sleep deprivation (PSD) consisted of 5 nights of maximum 4h of sleep per night...
February 7, 2018: Sleep
https://www.readbyqxmd.com/read/29395321/expressions-of-chemokines-and-their-receptors-in-the-brain-after-heat-stroke-induced-cortical-damage
#11
Yuh-Feng Lin, Tsung-Ta Liu, Chou-Hui Hu, Chun-Chi Chen, Jia-Yi Wang
Despite growing evidence that cytokines and chemokines are expressed in humans and rats after heat stress, the cellular mechanisms underlying the effects on the brain after heatstroke (HS) are not fully understood. In this study, we observed time course changes of chemokines in rat brain tissues and elucidated what kinds of cortical cells were affected after HS. Male SD rats were anesthetized and randomly separated into two groups as follows: (a) normothermic sham and (b) HS rats. Rats were sacrificed at different time points (0, 1, 3, 6, and 12h after heat exposure, n=5 in each group) to the end of the experiment in order to extract the mRNA/proteins of cortical tissues...
May 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#12
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
March 2018: Pain
https://www.readbyqxmd.com/read/29350434/the-cystine-glutamate-exchanger-xct-slc7a11-is-expressed-in-significant-concentrations-in-a-subpopulation-of-astrocytes-in-the-mouse-brain
#13
Sigrid Ottestad-Hansen, Qiu Xiang Hu, Virgine Veronique Follin-Arbelet, Eduard Bentea, Hideyo Sato, Ann Massie, Yun Zhou, Niels Christian Danbolt
The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes...
May 2018: Glia
https://www.readbyqxmd.com/read/29305855/microglia-derived-extracellular-vesicles-in-alzheimer-s-disease-a-double-edged-sword
#14
REVIEW
Teresa Trotta, Maria Antonietta Panaro, Antonia Cianciulli, Giorgio Mori, Adriana Di Benedetto, Chiara Porro
Extracellular vesicles (EVs), based on their origin or size, can be classified as apoptotic bodies, microvesicles (MVs)/microparticles (MPs), and exosomes. EVs are one of the new emerging modes of communication between cells that are providing new insights into the pathophysiology of several diseases. EVs released from activated or apoptotic cells contain specific proteins (signaling molecules, receptors, integrins, cytokines), bioactive lipids, nucleic acids (mRNA, miRNA, small non coding RNAs, DNA) from their progenitor cells...
February 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29298733/progressive-striatonigral-degeneration-in-a-transgenic-mouse-model-of-multiple-system-atrophy-translational-implications-for-interventional-therapies
#15
Violetta Refolo, Francesco Bez, Alexia Polissidis, Daniela Kuzdas-Wood, Edith Sturm, Martina Kamaratou, Werner Poewe, Leonidas Stefanis, M Angela Cenci, Marina Romero-Ramos, Gregor K Wenning, Nadia Stefanova
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by widespread oligodendroglial cytoplasmic inclusions of filamentous α-synuclein, and neuronal loss in autonomic centres, basal ganglia and cerebellar circuits. It has been suggested that primary oligodendroglial α-synucleinopathy may represent a trigger in the pathogenesis of MSA, but the mechanisms underlying selective vulnerability and disease progression are unclear. The post-mortem analysis of MSA brains provides a static final picture of the disease neuropathology, but gives no clear indication on the sequence of pathogenic events in MSA...
January 3, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29290406/elevated-expression-of-granulocyte-macrophage-colony-stimulating-factor-receptor-in-multiple-sclerosis-lesions
#16
Jaime Imitola, Javad Rasouli, Fumihiro Watanabe, Kader Mahajan, Aswhini D Sharan, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad Rostami
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease that disproportionately affects young adults, leading to disability and high costs to society. Infiltration of T cells and monocytes into the central nervous system (CNS) is critical for disease initiation and progression. However, despite a great deal of effort the molecular mechanisms by which immune cells initiate and perpetuate CNS damage in MS have not yet been elucidated. In experimental autoimmune encephalomyelitis (EAE), an animal model of MS, granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by pathogenic Th1 and Th17 cells is critical for the recruitment of monocytes into the CNS during the initial stage of disease...
April 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29288747/magnesium-sulfate-attenuates-brain-edema-by-lowering-aqp4-expression-and-inhibits-glia-mediated-neuroinflammation-in-a-rodent-model-of-eclampsia
#17
Xiaolan Li, Huishu Liu, Yuanyuan Yang
Eclampsia is characterized by high morbidity and mortality wordwide. Magnesium sulfate (MgSO4 ) is used frequently as a prophylaxis for eclamptic seizure in clinical settings. However, the underlying mechanism is less studied, we have previously demonstrated that MgSO4 pretreatment decreases eclampsia-like seizure threshold. Here, we further evaluated the hypothesis that MgSO4 exert neuroprotective actions in eclampsia-like rats model by ameliorating neuroinflammation and brain edema. In this study, the eclampsia-like model was established by administering lipopolysaccharide plus pentylenetetrazol in pregnant Sprague-Dawley rats...
December 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29284508/inflammatory-dysregulation-of-monocytes-in-pediatric-patients-with-obsessive-compulsive-disorder
#18
Natalia Rodríguez, Astrid Morer, E Azucena González-Navarro, Carles Serra-Pages, Daniel Boloc, Teresa Torres, Susana García-Cerro, Sergi Mas, Patricia Gassó, Luisa Lázaro
BACKGROUND: Although the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls. METHODS: We determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14high CD16-), intermediate (CD14high CD16low ), and non-classical (CD14low CD16high ) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls...
December 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29258921/the-choroid-plexus-epithelium-as-a-novel-player-in-the-stomach-brain-axis-during-helicobacter-infection
#19
N Gorlé, C Blaecher, E Bauwens, C Vandendriessche, S Balusu, J Vandewalle, C Van Cauwenberghe, E Van Wonterghem, G Van Imschoot, C Liu, R Ducatelle, C Libert, F Haesebrouck, A Smet, R E Vandenbroucke
Several studies suggest a link between shifts in gut microbiota and neurological disorders. Recently, we reported a high prevalence of Helicobacter suis (H. suis) in patients with Parkinson's disease. Here, we evaluated the effect of gastric H. suis infection on the brain in mice. One month of infection with H. suis resulted in increased brain inflammation, reflected in activation of microglia and cognitive decline. Additionally, we detected choroid plexus inflammation and disruption of the epithelial blood-cerebrospinal fluid (CSF) barrier upon H...
March 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29251592/the-role-of-microglia-and-their-cx3cr1-signaling-in-adult-neurogenesis-in-the-olfactory-bulb
#20
Ronen Reshef, Elena Kudryavitskaya, Haran Shani-Narkiss, Batya Isaacson, Neta Rimmerman, Adi Mizrahi, Raz Yirmiya
Microglia play important roles in perinatal neuro- and synapto-genesis. To test the role of microglia in these processes during adulthood, we examined the effects of microglia depletion, via treatment of mice with the CSF-1 receptor antagonist PLX5622, and abrogated neuronal-microglial communication in CX3C receptor-1 deficient ( Cx3cr1-/- ) mice. Microglia depletion significantly lowered spine density in young (developing) but not mature adult-born-granule-cells (abGCs) in the olfactory bulb. Two-photon time-lapse imaging indicated that microglia depletion reduced spine formation and elimination...
December 18, 2017: ELife
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