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https://www.readbyqxmd.com/read/28900063/-translational-research-on-neuropsychiatric-disorders-focusing-on-microglia-hypothesis
#1
Takahiro A Kato, Masahiro Ohgidani, Shigenobu Kanba
Microglia-immune cells in the brain-have recently been highlighted to understand the pathophysiology of psychiatric disorders such as schizophrenia, depression, and autism. In this review paper, we introduce the microglia hypothesis for psychiatric disorders. In addition, we introduce our novel translational research approach to psychiatric disorders using microglia-like (iMG) cells directly induced from human blood, these iMG cells can be produced from peripheral monocytes within two weeks using two cytokines: granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-34 (IL-34)...
September 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28886491/interleukin-34-from-pathogenesis-to-clinical-applications
#2
REVIEW
Muhammad Baghdadi, Hiraku Endo, Yoshino Tanaka, Haruka Wada, Ken-Ichiro Seino
Interleukin-34 (IL-34) is a hematopoietic cytokine that was described for the first time in 2008 as a second ligand of CSF1R in addition to M-CSF. IL-34 and M-CSF share no sequence homology, but have similar functions, affecting the biology of myeloid cell lineage. In contrast to M-CSF, IL-34 shows unique signaling and expression patterns. Physiologically, IL-34 expression is restricted to epidermis and CNS, acting as a regulator of Langerhans cells and microglia, respectively. However, IL-34 expression can be induced and regulated by NF-κB under pathological conditions...
September 5, 2017: Cytokine
https://www.readbyqxmd.com/read/28821831/targeted-inhibition-of-rage-in-substantia-nigra-of-rats-blocks-6-ohda-induced-dopaminergic-denervation
#3
Juciano Gasparotto, Camila Tiefensee Ribeiro, Rafael Calixto Bortolin, Nauana Somensi, Thallita Kelly Rabelo, Alice Kunzler, Natália Cabral Souza, Matheus Augusto de Bittencourt Pasquali, José Claudio Fonseca Moreira, Daniel Pens Gelain
The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806641/acute-ethanol-administration-results-in-a-protective-cytokine-and-neuroinflammatory-profile-in-traumatic-brain-injury
#4
Akila Chandrasekar, Florian Olde Heuvel, Annette Palmer, Birgit Linkus, Albert C Ludolph, Tobias M Boeckers, Borna Relja, Markus Huber-Lang, Francesco Roselli
Ethanol intoxication is a common comorbidity in traumatic brain injury. To date, the effect of ethanol on TBI pathogenic cascades and resulting outcomes remains debated. A closed blunt weight-drop murine TBI model has been implemented to investigate behavioral (by sensorimotor and neurological tests), and neuro-immunological (by tissue cytokine arrays and immuno-histology) effects of ethanol intoxication on TBI. The effect of the occurrence of traumatic intracerebral hemorrhage was also studied. The results indicate that ethanol pretreatment results in a faster and better recovery after TBI with reduced infiltration of leukocytes and reduced microglia activation...
August 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28793053/cerebrospinal-fluid-contacting-nucleus-mediates-nociception-via-release-of-fractalkine
#5
Q Q Zhou, S S Chen, Q Q Zhang, P F Liu, H Z Fang, Y Yang, L C Zhang
Increasing evidence suggests that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia...
August 7, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28769786/mild-inflammatory-profile-without-gliosis-in-the-c-rel-deficient-mouse-modeling-a-late-onset-parkinsonism
#6
Vanessa Porrini, Mariana Mota, Edoardo Parrella, Arianna Bellucci, Marina Benarese, Lara Faggi, Paolo Tonin, Pier F Spano, Marina Pizzi
The impact of neuroinflammation and microglial activation to Parkinson's disease (PD) progression is still debated. Post-mortem analysis of PD brains has shown that neuroinflammation and microgliosis are key features of end-stage disease. However, microglia neuroimaging studies and evaluation of cerebrospinal fluid (CSF) cytokines in PD patients at earlier stages do not support the occurrence of a pronounced neuroinflammatory process. PD animal models recapitulating the motor and non-motor features of the disease, and the slow and progressive neuropathology, can be of great advantage in understanding whether and how neuroinflammation associates with the onset of symptoms and neuronal loss...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28759224/n-pivaloyloxy-alkoxy-carbonyl-prodrugs-of-the-glutamine-antagonist-6-diazo-5-oxo-l-norleucine-don-as-a-potential-treatment-for-hiv-associated-neurocognitive-disorders
#7
Michael T Nedelcovych, Lukáš Tenora, Boe-Hyun Kim, Jennifer Kelschenbach, Wei Chao, Eran Hadas, Andrej Jančařík, Eva Prchalová, Sarah C Zimmermann, Ranjeet P Dash, Alexandra J Gadiano, Caroline Garrett, Georg Furtmüller, Byoungchol Oh, Gerald Brandacher, Jesse Alt, Pavel Majer, David J Volsky, Rana Rais, Barbara S Slusher
Aberrant excitatory neurotransmission associated with overproduction of glutamate has been implicated in the development of HIV-associated neurocognitive disorders (HAND). The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 14) attenuates glutamate synthesis in HIV-infected microglia/macrophages, offering therapeutic potential for HAND. We show that 14 prevents manifestation of spatial memory deficits in chimeric EcoHIV-infected mice, a model of HAND. 14 is not clinically available, however, because its development was hampered by peripheral toxicities...
August 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28714751/antidepressant-efficacy-of-electroconvulsive-therapy-is-associated-with-a-reduction-of-the-innate-cellular-immune-activity-in-the-cerebrospinal-fluid-in-patients-with-depression
#8
Laura Kranaster, Carolin Hoyer, Suna S Aksay, Jan Malte Bumb, Norbert Müller, Peter Zill, Markus J Schwarz, Alexander Sartorius
OBJECTIVES: A bidirectional link between the antidepressant effects of electroconvulsive therapy (ECT) and the modulation of the immune system has been proposed. To elucidate the interplay between antidepressant treatment and macrophage/microglia activation in humans, we performed a study on the effects of the antidepressant treatment by ECT on markers of macrophage/microglia activation in patients with depression. METHODS: We measured six different markers (IL-6, neopterin, sCD14, sCD163 MIF and MCP1) of macrophage/microglia activation in the cerebrospinal fluid (CSF) and blood of 12 patients with a severe, treatment-resistant depressive episode before and after a course of ECT...
August 9, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28683563/modulation-of-hematopoietic-lineage-specification-impacts-trem2-expression-in-microglia-like-cells-derived-from-human-stem-cells
#9
Peter J Amos, Susan Fung, Amanda Case, Jerusalem Kifelew, Leah Osnis, Carole L Smith, Kevin Green, Alipi Naydenov, Macarena Aloi, Jesse J Hubbard, Aravind Ramakrishnan, Gwenn A Garden, Suman Jayadev
Microglia are the primary innate immune cell type in the brain, and their dysfunction has been linked to a variety of central nervous system disorders. Human microglia are extraordinarily difficult to obtain for experimental investigation, limiting our ability to study the impact of human genetic variants on microglia functions. Previous studies have reported that microglia-like cells can be derived from human monocytes or pluripotent stem cells. Here, we describe a reproducible relatively simple method for generating microglia-like cells by first deriving embryoid body mesoderm followed by exposure to microglia relevant cytokines...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28646409/neuroprotective-effects-of-g-csf-administration-in-microglia-mediated-reactive-t-cell-activation-in-vitro
#10
Wei Peng
G-CSF is a growth factor that has known neuroprotective effects in a variety of experimental brain injury models. As both antigen-presenting microglia and reactive T cells are key components in the development and progression of EAE, the aim of this study is to investigate the neuroprotective effects of recombinant human G-CSF, as administered in microglia-mediated reactive T cell assay in vitro. Our results indicate that G-CSF treatment has no apparent effect for the resting un-activated microglia. G-CSF pre-protection of microglia increased protective cytokine IL-4 production and effectively inhibited the productions of NO and other inflammatory mediators (IFN-γ, TNF-α, IL-1β, IL-17, and chemokine MCP-1) after LPS stimulation...
August 2017: Immunologic Research
https://www.readbyqxmd.com/read/28598083/-expressions-of-spinal-macrophage-colony-stimulating-factor-and-its-receptor-csf-1r-in-the-development-ofcomplicated-regional-pain-symptom-i
#11
Zhi-Min Liao, Yu-Ying Tang, Yang-Chun Zheng, Dan Xu
OBJECTIVES: To study the changes of mechanical allodynia and temperature hyperalgesia, as well as the expression of the spinal macrophage colony stimulating factor (M-CSF) and its receptor CSF-1R during the development of complicated regional pain symptom I(CRPS I). METHODS: The animal model of CRPS I was established using prolonged ischemia-reperfusion injury of rodent left hindpaw. The mechanical allodynia and temperature hyperalgesia of ipsilateral hindpaw were continuously measured for 14 d after reperfusion, and the expressions of spinal M-CSF and CSF-1R in ipsilateral spinal cord horn were measured with immunofluorescence technique on day 3, day 7 and day 14 after reperfusion...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28579942/voluntary-exercise-promotes-glymphatic-clearance-of-amyloid-beta-and-reduces-the-activation-of-astrocytes-and-microglia-in-aged-mice
#12
Xiao-Fei He, Dong-Xu Liu, Qun Zhang, Feng-Ying Liang, Guang-Yan Dai, Jin-Sheng Zeng, Zhong Pei, Guang-Qing Xu, Yue Lan
Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood-brain barrier (BBB) or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer's disease (AD), but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28544775/potentiation-of-spinal-glutamatergic-response-in-the-neuron-glia-interactions-underlies-the-intrathecal-il-1%C3%AE-induced-thermal-hyperalgesia-in-rats
#13
Chun-Sung Sung, Zhi-Hong Wen, Chien-Wei Feng, Chun-Hong Chen, Shi-Ying Huang, Nan-Fu Chen, Wu-Fu Chen, Chih-Shung Wong
AIMS: We previously demonstrated that intrathecal IL-1β upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1β-induced nociception in rats. METHODS: The pretreatment effects of MK-801 (5 μg), minocycline (20 μg), and SB203580 (5 μg) on intrathecal IL-1β (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies...
July 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28539349/sleep-loss-promotes-astrocytic-phagocytosis-and-microglial-activation-in-mouse-cerebral-cortex
#14
Michele Bellesi, Luisa de Vivo, Mattia Chini, Francesca Gilli, Giulio Tononi, Chiara Cirelli
We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain's resident innate immune cells, was unknown...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28534275/sex-bias-in-pathogenesis-of-autoimmune-neuroinflammation-relevance-for-dimethyl-fumarate-immunomodulatory-anti-oxidant-action
#15
Zorica Stojić-Vukanić, Jelena Kotur-Stevuljević, Mirjana Nacka-Aleksić, Duško Kosec, Ivana Vujnović, Ivan Pilipović, Mirjana Dimitrijević, Gordana Leposavić
In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28526328/acrylamide-induced-neurotoxicity-in-primary-astrocytes-and-microglia-roles-of-the-nrf2-are-and-nf-%C3%AE%C2%BAb-pathways
#16
Mengyao Zhao, Fu Sheng Lewis Wang, Xiaosong Hu, Fang Chen, Hing Man Chan
Acrylamide (AA) is a common food contaminant formed during food heat processing that has neurotoxic effects. We hypothesize that AA induces oxidative stress in astrocytes and microglia, leading to neurotoxicity. Oxidative status, translocation of Nrf2 and NF-κB, and related down-stream targets were measured in primary astrocytes and microglia obtained from BALB/c mice. The results showed that AA increased reactive oxygen species (ROS) formation and reduced glutathione levels, causing successive events associated with oxidative stress, including 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine adduct formation, in both cell types...
May 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28521131/diverse-requirements-for-microglial-survival-specification-and-function-revealed-by-defined-medium-cultures
#17
Christopher J Bohlen, F Chris Bennett, Andrew F Tucker, Hannah Y Collins, Sara B Mulinyawe, Ben A Barres
Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#18
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28480882/dysfunction-of-microglial-stat3-alleviates-depressive-behavior-via-neuron-microglia-interactions
#19
Sun-Ho Kwon, Jeong-Kyu Han, Moonseok Choi, Yong-Jin Kwon, Sung Joon Kim, Eun Hee Yi, Jae-Cheon Shin, Ik-Hyun Cho, Byung-Hak Kim, Sang Jeong Kim, Sang-Kyu Ye
Neuron-microglia interactions have a crucial role in maintaining the neuroimmune system. The balance of neuroimmune system has emerged as an important process in the pathophysiology of depression. However, how neuron-microglia interactions contribute to major depressive disorders has been poorly understood. Herein, we demonstrated that microglia-derived synaptic changes induced antidepressive-like behavior by using microglia-specific signal transducer and activator of transcription 3 (STAT3) knockout (KO) (STAT3(fl/fl);LysM-Cre(+/-)) mice...
September 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28458957/dramatic-effect-of-oral-csf-1r-kinase-inhibitor-on-retinal-microglia-revealed-by-in-vivo-scanning-laser-ophthalmoscopy
#20
Andreas Ebneter, Despina Kokona, Joël Jovanovic, Martin S Zinkernagel
This report provides sound evidence that the small molecule pharmaceutical PLX5622, a highly selective CSF-1R kinase inhibitor, crosses the blood-retina barrier and suppresses microglia activity. Members of this class of drug are in advanced clinical development stages and may represent a novel approach to modulate ocular inflammatory processes.
April 2017: Translational Vision Science & Technology
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