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Microglia and migration

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https://www.readbyqxmd.com/read/28426964/ipsc-derived-human-microglia-like-cells-to-study-neurological-diseases
#1
Edsel M Abud, Ricardo N Ramirez, Eric S Martinez, Luke M Healy, Cecilia H H Nguyen, Sean A Newman, Andriy V Yeromin, Vanessa M Scarfone, Samuel E Marsh, Cristhian Fimbres, Chad A Caraway, Gianna M Fote, Abdullah M Madany, Anshu Agrawal, Rakez Kayed, Karen H Gylys, Michael D Cahalan, Brian J Cummings, Jack P Antel, Ali Mortazavi, Monica J Carson, Wayne W Poon, Mathew Blurton-Jones
Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28417486/age-specific-function-of-%C3%AE-5%C3%AE-1-integrin-in-microglial-migration-during-early-colonization-of-the-developing-mouse-cortex
#2
Sophie Marie-Thérèse Smolders, Nina Swinnen, Sofie Kessels, Kaline Arnauts, Silke Smolders, Barbara Le Bras, Jean-Michel Rigo, Pascal Legendre, Bert Brône
Microglia, the immune cells of the central nervous system, take part in brain development and homeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonize the brain mainly through intensive migration. During development, microglial migration speed declines which suggests that their interaction with the microenvironment changes. However, the matrix-cell interactions allowing dispersion within the parenchyma are unknown. Therefore, we aimed to better characterize the migration behavior and to assess the role of matrix-integrin interactions during microglial migration in the embryonic brain ex vivo...
April 18, 2017: Glia
https://www.readbyqxmd.com/read/28417261/neutrophil-infiltration-and-matrix-metalloproteinase-9-in-lacunar-infarction
#3
Wolfgang Walz, Francisco S Cayabyab
We use the modified pial vessel disruption rat model to elucidate the cellular and molecular mechanisms of cavitation as it plays a role in lacunar infarction. Here we discuss the similarities between the genesis of pulmonary cavitation in various animal models and lacunar infarction in the cerebral cortex of rats. Both pathological processes involve the creation of a cavity surrounded by fibroblasts or reactive astrocytes. A crucial step in both, the lung and the cerebral cortex, appears to be the migration of neutrophils across the endothelial barrier into the parenchyma...
April 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28416692/immunomodulation-accelerated-neuronal-regeneration-following-selective-rod-photoreceptor-cell-ablation-in-the-zebrafish-retina
#4
David T White, Sumitra Sengupta, Meera T Saxena, Qingguo Xu, Justin Hanes, Ding Ding, Hongkai Ji, Jeff S Mumm
Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28382975/radiation-induces-progenitor-cell-death-microglia-activation-and-blood-brain-barrier-damage-in-the-juvenile-rat-cerebellum
#5
Kai Zhou, Martina Boström, C Joakim Ek, Tao Li, Cuicui Xie, Yiran Xu, Yanyan Sun, Klas Blomgren, Changlian Zhu
Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient's quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381303/retention-of-normal-glia-function-by-an-isoform-selective-protein-kinase-inhibitor-drug-candidate-that-modulates-cytokine-production-and-cognitive-outcomes
#6
Zhengqiu Zhou, Adam D Bachstetter, Claudia B Späni, Saktimayee M Roy, D Martin Watterson, Linda J Van Eldik
BACKGROUND: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates...
April 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28380296/n6-substituted-5-n-methylcarbamoyl-4-selenoadenosines-as-potent-and-selective-a3-adenosine-receptor-agonists-with-unusual-sugar-puckering-and-nucleobase-orientation
#7
Jinha Yu, Long Xuan Zhao, Jongmi Park, Hyuk Woo Lee, Pramod K Sahu, Minghua Cui, Steven M Moss, Eva Hammes, Eugene Warnick, Zhan-Guo Gao, Minsoo Noh, Sun Choi, Hee-Chul Ahn, Jungwon Choi, Kenneth A Jacobson, Lak Shin Jeong
Potent and selective A3 adenosine receptor (AR) agonists were identified by replacement of 4'-oxo- or 4'-thionucleosides with bioisosteric selenium. Unlike previous agonists, 4'-seleno analogues preferred a glycosidic syn conformation and a South sugar puckering, as shown in the X-ray crystal structure of 5'-N-methylcarbamoyl derivative 3p. Among compounds tested, N6-3-iodobenzyl analogue 3d was found to be the most potent A3AR full agonist (Ki = 0.57 nM), which was ≥ 800- and 1900-fold selective for A1 and A2AARs, respectively...
April 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28370426/intramembranous-processing-by-%C3%AE-secretase-regulates-reverse-signaling-of-ephrin-b2-in-migration-of-microglia
#8
Nadja Kemmerling, Patrick Wunderlich, Sandra Theil, Bettina Linnartz-Gerlach, Nils Hersch, Bernd Hoffmann, Michael T Heneka, Bart de Strooper, Harald Neumann, Jochen Walter
The Eph-ephrin system plays pivotal roles in cell adhesion and migration. The receptor-like functions of the ephrin ligands allow the regulation of intracellular processes via reverse signaling. γ-Secretase mediated processing of ephrin-B has previously been linked to activation of Src, a kinase crucial for focal adhesion and podosome phosphorylation. Here, we analyzed the role of γ-secretase in the stimulation of reverse ephrin-B2 signaling in the migration of mouse embryonic stem cell derived microglia...
April 3, 2017: Glia
https://www.readbyqxmd.com/read/28367116/microglial-intracellular-ca-2-signaling-in-synaptic-development-and-its-alterations-in-neurodevelopmental-disorders
#9
REVIEW
Yoshito Mizoguchi, Akira Monji
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in social interaction, difficulties with language and repetitive/restricted behaviors. Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) when they are activated in response to immunological stimuli. Recent in vivo imaging has shown that microglia sculpt and refine the synaptic circuitry by removing excess and unwanted synapses and be involved in the development of neural circuits or synaptic plasticity thereby maintaining the brain homeostasis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28359543/monitoring-in-vivo-function-of-cortical-microglia
#10
REVIEW
Bianca Brawek, Olga Garaschuk
Microglia, the innate immune cells of the brain, are becoming increasingly recognized as an important player both in the context of physiological brain function and brain pathology. To fulfill their executive functions microglia can modify their morphology, migrate or move their processes in a directed fashion, and modify the intracellular Ca(2+) dynamics leading to modifications in gene expression, phagocytosis, release of cytokines and other inflammation markers, etc. Here we describe the recently developed tools enabling in vivo monitoring of morphology and Ca(2+) signaling of microglia and show how these techniques may be used for examining microglial function in healthy and diseased brain...
March 14, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28340576/polysaccharides-from-ganoderma-lucidum-attenuate-microglia-mediated-neuroinflammation-and-modulate-microglial-phagocytosis-and-behavioural-response
#11
Qing Cai, Yuanyuan Li, Gang Pei
BACKGROUND: Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28336953/palmitoylethanolamide-induces-microglia-changes-associated-with-increased-migration-and-phagocytic-activity-involvement-of-the-cb2-receptor
#12
F Guida, L Luongo, S Boccella, M E Giordano, R Romano, G Bellini, I Manzo, A Furiano, A Rizzo, R Imperatore, F A Iannotti, E D'Aniello, F Piscitelli, F Sca Rossi, L Cristino, V Di Marzo, V de Novellis, S Maione
The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323006/the-role-of-sumoylation-in-cerebral-hypoxia-and-ischemia
#13
REVIEW
Myriam Peters, Betty Wielsch, Johannes Boltze
The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous processes in eukaryotic cells. SUMOylation also represents a key response and adaption mechanism to different forms of metabolic stress. The central nervous system (CNS) and neurons in particular are highly susceptible to hypoxic-ischemic stress due to the lack of significant oxygen and energy reserves. SUMOylation is observed in many molecular responses to metabolic stress in the brain, and is therefore supposed to represent an endogenous neuroprotective mechanism...
March 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28300326/hur-promotes-the-molecular-signature-and-phenotype-of-activated-microglia-implications-for-amyotrophic-lateral-sclerosis-and-other-neurodegenerative-diseases
#14
Prachi Matsye, Lei Zheng, Ying Si, Soojin Kim, Wenyi Luo, David K Crossman, Preston E Bratcher, Peter H King
In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), chronic activation of microglia contributes to disease progression. Activated microglia produce cytokines, chemokines, and other factors that normally serve to clear infection or damaged tissue either directly or through the recruitment of other immune cells. The molecular program driving this phenotype is classically linked to the transcription factor NF-κB and characterized by the upregulation of proinflammatory factors such as IL-1β, TNF-α, and IL-6...
March 16, 2017: Glia
https://www.readbyqxmd.com/read/28298640/combined-transplantation-of-human-mesenchymal-stem-cells-and-human-retinal-progenitor-cells-into-the-subretinal-space-of-rcs-rats
#15
Linghui Qu, Lixiong Gao, Haiwei Xu, Ping Duan, Yuxiao Zeng, Yong Liu, Zheng Qin Yin
Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293066/udp-induced-phagocytosis-and-atp-stimulated-chemotactic-migration-are-impaired-in-stim1-microglia-in-vitro-and-in-vivo
#16
Hye Min Lim, Heo Woon, Jung Woo Han, Yoshihiro Baba, Tomohiro Kurosaki, Min Goo Lee, Joo Young Kim
STIM1 is the only currently known intracellular calcium sensor that functions as the calcium influx regulator controlling immune cell activation. STIM1 function in immune cell calcium signalling has been studied extensively; however, its role in microglia, innate immune cells in brain, has not been fully understood. Here, we report that STIM1(-/-) murine microglia lost store-operated calcium influx and displayed aberrant immunological functions. Microglial functions regulated by chronic and global [Ca(2+)]i changes were reduced significantly, including cytokine releases and opsonin-dependent phagocytosis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#17
Anna Gieryng, Dominika Pszczolkowska, Kacper A Walentynowicz, Wenson D Rajan, Bozena Kaminska
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells consist of CNS resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells (MDSCs), and T lymphocytes...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28280458/jmv5656-a-novel-derivative-of-tlqp-21-triggers-the-activation-of-a-calcium-dependent-potassium-outward-current-in-microglial-cells
#18
Ilaria Rivolta, Anna Binda, Laura Molteni, Laura Rizzi, Elena Bresciani, Roberta Possenti, Jean-Alain Fehrentz, Pascal Verdié, Jean Martinez, Robert J Omeljaniuk, Vittorio Locatelli, Antonio Torsello
TLQP-21 (TLQPPASSRRRHFHHALPPAR) is a multifunctional peptide that is involved in the control of physiological functions, including feeding, reproduction, stress responsiveness, and general homeostasis. Despite the huge interest in TLQP-21 biological activity, very little is known about its intracellular mechanisms of action. In microglial cells, TLQP-21 stimulates increases of intracellular Ca(2+) that may activate functions, including proliferation, migration, phagocytosis and production of inflammatory molecules...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28279751/blockade-of-ccr5-receptor-prevents-m2-microglia-phenotype-in-a-microglia-glioma-paradigm
#19
Emilia Laudati, Diego Currò, Pierluigi Navarra, Lucia Lisi
Microglia express chemokines and their cognate receptors that were found to play important roles in many processes required for tumor development, such as tumor growth, proliferation, invasion, and angiogenesis. Among the chemokine receptor, CCR5 have been documented in different cancer models; in particular, CCR5 is highly expressed in human glioblastoma, where it is associated to poor prognosis. In the present study, we investigated the effect of CCR5 receptor blockade on a paradigm of microglia-glioma interaction; the CCR5 blocker maraviroc (MRV) was used as a pharmacological tool...
March 6, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28275337/tir-domain-containing-adapter-inducing-interferon-%C3%AE-trif-is-essential-for-mptp-induced-dopaminergic-neuroprotection-via-microglial-cell-m1-m2-modulation
#20
Minghui Shan, Sen Lin, Shurong Li, Yuchen Du, Haixia Zhao, Huarong Hong, Ming Yang, Xi Yang, Yongmei Wu, Liyi Ren, Jiali Peng, Jing Sun, Hongli Zhou, Bingyin Su
Dynamic changes of two phenotypes of microglia, M1 and M2, are critically associated with the neurodegeneration of Parkinson's disease. However, the regulation of the M1/M2 paradigm is still unclear. In the MPTP induced neurodegeneration model, we examined the concentration of dopamine (DA) related metabolites and the survival of tyrosine hydroxylase (TH) positive cells in WT and Trif(-/-) mice. In in vitro experiments, MN9D cells were co-cultured with BV2 cells to mimic the animal experiments. Inhibition of TRIF aggravated TH+ cell loss, and DA-related metabolites decreased...
2017: Frontiers in Cellular Neuroscience
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