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microglia process outgrowth

Jing Sun, Xiaoyu Pan, Line I Christiansen, Xiao-Long Yuan, Kerstin Skovgaard, Dereck E W Chatterton, Sanne S Kaalund, Fei Gao, Per T Sangild, Stanislava Pankratova
BACKGROUND: Necrotizing enterocolitis (NEC) is an acute gut inflammatory disorder that occurs in preterm infants in the first weeks after birth. Infants surviving NEC often show impaired neurodevelopment. The mechanisms linking NEC lesions with later neurodevelopment are poorly understood but may include proinflammatory signaling in the immature brain. Using preterm pigs as a model for preterm infants, we hypothesized that severe intestinal NEC lesions are associated with acute effects on the developing hippocampus...
June 9, 2018: Journal of Neuroinflammation
Jennifer Shih, Chris G Dulla
Madry et al. (2018) show that the two-pore potassium channel THIK-1 is tonically active in microglia and promotes microglial ramification and surveillance of the brain parenchyma. Interestingly, THIK-1 is not essential to damage-induced outgrowth of microglial processes but is critical to microglial IL-1β release.
January 17, 2018: Neuron
Christian Madry, Vasiliki Kyrargyri, I Lorena Arancibia-Cárcamo, Renaud Jolivet, Shinichi Kohsaka, Robert M Bryan, David Attwell
Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ramification, or surveillance...
January 17, 2018: Neuron
Fargol Mazaheri, Nicolas Snaidero, Gernot Kleinberger, Charlotte Madore, Anna Daria, Georg Werner, Susanne Krasemann, Anja Capell, Dietrich Trümbach, Wolfgang Wurst, Bettina Brunner, Sebastian Bultmann, Sabina Tahirovic, Martin Kerschensteiner, Thomas Misgeld, Oleg Butovsky, Christian Haass
Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration. In the brain, TREM2 is predominantly expressed in microglia. Several disease-associated TREM2 variants result in a loss of function by reducing microglial phagocytosis, impairing lipid sensing, preventing binding of lipoproteins and affecting shielding of amyloid plaques. We here investigate the consequences of TREM2 loss of function on the microglia transcriptome...
July 2017: EMBO Reports
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
Sandra Oliveira Braz, Andrea Cruz, Andrea Lobo, Joana Bravo, Joana Moreira-Ribeiro, Isabel Pereira-Castro, Jaime Freitas, Joao B Relvas, Teresa Summavielle, Alexandra Moreira
The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood...
June 2017: Biochimica et Biophysica Acta
Kitty Reemst, Stephen C Noctor, Paul J Lucassen, Elly M Hol
Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology...
2016: Frontiers in Human Neuroscience
Ulrich H Weidle, Fabian Birzele, Gwendlyn Kollmorgen, Rüdiger Rüger
Brain metastases outnumber the incidence of brain tumors by a factor of ten. Patients with brain metastases have a dismal prognosis and current treatment modalities achieve only a modest clinical benefit. We discuss the process of brain metastasis with respect to mechanisms and involved targets to outline options for therapeutic intervention and focus on breast and lung cancer, as well as melanoma. We describe the process of penetration of the blood-brain-barrier (BBB) by disseminated tumor cells, establishment of a metastatic niche, colonization and outgrowth in the brain parenchyma...
July 2016: Cancer Genomics & Proteomics
Chunshuai Wu, Zhiming Cui, Yonghua Liu, Jinlong Zhang, Wensen Ding, Song Wang, Guofeng Bao, Guanhua Xu, Yuyu Sun, Jiajia Chen
Traumatic spinal cord injury is one of the most common and severe problems for using NGF to promote the neurite outgrowth of survival neurons. EHD1 regulates and controls the endocytosis and transportation of neurotrophins and transmembrane cargo via recycling endosome for neurite outgrowth. TrkA is particularly considered to be a functional specific recepter in the cell membrane for NGF and is activated upon NGF binding. The transcytosis of TrkA is dependent on Rab11 recycling endosomes and is promoted by NGF signaling itself at the axon terminal...
August 2016: International Journal of Developmental Neuroscience
Mrinmay Chakrabarti, Alexander J McDonald, J Will Reed, Melissa A Moss, Bhaskar C Das, Swapan K Ray
Retinoids, which are vitamin A derivatives, interact through retinoic acid receptors (RARs) and retinoid X receptors (RXRs) and have profound effects on several physiological and pathological processes in the brain. The presence of retinoic acid signaling is extensively detected in the adult central nervous system, including the amygdala, cortex, hypothalamus, hippocampus, and other brain areas. Retinoids are primarily involved in neural patterning, differentiation, and axon outgrowth. Retinoids also play a key role in the preservation of the differentiated state of adult neurons...
2016: Journal of Alzheimer's Disease: JAD
Yinquan Fang, Jun Yan, Chenhui Li, Xiao Zhou, Lemeng Yao, Tao Pang, Ming Yan, Luyong Zhang, Lei Mao, Hong Liao
Microglia have been proposed to play a pivotal role in the inflammation response of the CNS by expressing a range of proinflammatory enzymes and cytokines under pathological stimulus. Our previous study has confirmed that Nogo receptor (NgR), an axon outgrowth inhibition receptor, is also expressed on microglia and regulates cell adhesion and migration behavior in vitro. In the present study, we further investigated the proinflammatory effects and possible mechanisms of Nogo on microglia in vitro. In this study, Nogo peptide, Nogo-P4, a 25-amino acid core inhibitory peptide sequence of Nogo-66, was used...
November 27, 2015: Journal of Biological Chemistry
Yaping Wang, Lin Yang, Donglin Yang
Activated microglia plays an important role in monitoring the microenvironment and prune neural process in healthy neural tissue, in order to maintain synaptic homeostasis. However, hyperactive microglia may release various cytotoxic factors and induce neuroinflammation, which cause neuronal damages leading to neurodegenerative diseases. Tanshinone IIA (TSA), an extract from traditional Chinese medicine, features potent anti-apoptotic and anti-inflammatory effects both in vitro and in vivo. But little is known on the effects of TSA on microglial-over-activation-induced neural impairments...
July 2015: Neurochemical Research
Zhongwang Yu, Dingya Sun, Jifeng Feng, Weixing Tan, Xue Fang, Ming Zhao, Xiaolin Zhao, Yingyan Pu, Aijun Huang, Zhenghua Xiang, Li Cao, Cheng He
The major challenge for progressive multiple sclerosis therapy is the promotion of remyelination from inflammation-induced demyelination. A switch from an M1- to an M2-dominant polarization of microglia is critical in these repair processes. In this study, we identified the homeobox gene msh-like homeobox-3 (Msx3) as a new pivotal regulator for microglial polarization. MSX3 was induced during microglia M2 polarization and repressed in M1 cells. The expression of MSX3 in microglia was dynamically regulated during experimental autoimmune encephalomyelitis (EAE), which is an animal model of multiple sclerosis...
April 22, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jenni Neubert, Susanne Wagner, Jürgen Kiwit, Anja U Bräuer, Jana Glumm
The physicochemical properties of superparamagnetic iron oxide nanoparticles (SPIOs) enable their application in the diagnostics and therapy of central nervous system diseases. However, since crucial information regarding side effects of particle-cell interactions within the central nervous system is still lacking, we investigated the influence of novel very small iron oxide particles or the clinically approved ferucarbotran or ferumoxytol on the vitality and morphology of brain cells. We exposed primary cell cultures of microglia and hippocampal neurons, as well as neuron-glia cocultures to varying concentrations of SPIOs for 6 and/or 24 hours, respectively...
2015: International Journal of Nanomedicine
Hannah Scheiblich, Gerd Bicker
Clearance of infected and apoptotic neuronal corpses during inflammatory conditions is a fundamental process to create a favorable environment for neuronal recovery. Microglia are the resident immune cells and the predominant phagocytic cells of the CNS, showing a multitude of cellular responses upon activation. Here, we investigated in functional assays how the CO generating enzyme heme oxygenase 1 (HO-1) influences BV-2 microglial migration, clearance of debris, and neurite outgrowth of human NT2 neurons...
August 2015: Developmental Neurobiology
Lasse Dissing-Olesen, Jeffrey M LeDue, Ravi L Rungta, Jasmin K Hefendehl, Hyun B Choi, Brian A MacVicar
Microglia are morphologically dynamic cells that rapidly extend their processes in response to various stimuli including extracellular ATP. In this study, we tested the hypothesis that stimulation of neuronal NMDARs trigger ATP release leading to communication with microglia. We used acute mouse hippocampal brain slices and two-photon laser scanning microscopy to study microglial dynamics and developed a novel protocol for fixation and immunolabeling of microglia processes. Similar to direct topical ATP application in vivo, short multiple applications of NMDA triggered transient microglia process outgrowth that was reversible and repeatable indicating that this was not due to excitotoxic damage...
August 6, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
D E Korzhevskiĭ, M V Lentsman, O V Kirik, V A Otellin
The aim of the study was to evaluate, by using immunohistochemistry (demonstration of Iba-1 protein), the morphological features of the rat hippocampal microglia and to describe its cellular types during the response to a single total brain ischemia of 12 min duration. The results obtained suggest the existence of several morphologic types of microgliocytes in the intact hippocampus, while some more types appear in response to ischemic lesion of neurons. These changes in general population of the hippocampal microgliocytes is related to their functional activation...
2012: Morfologi︠a︡
Mark S Moehle, Philip J Webber, Tonia Tse, Nour Sukar, David G Standaert, Tara M DeSilva, Rita M Cowell, Andrew B West
Missense mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), and common genetic variation in LRRK2 modifies susceptibility to Crohn's disease and leprosy. High levels of LRRK2 expression in peripheral monocytes and macrophages suggest a role for LRRK2 in these cells, yet little is known about LRRK2 expression and function in immune cells of the brain. Here, we demonstrate a role for LRRK2 in mediating microglial proinflammatory responses and morphology. In a murine model of neuroinflammation, we observe robust induction of LRRK2 in microglia...
February 1, 2012: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mari Kitayama, Masaki Ueno, Toru Itakura, Toshihide Yamashita
By causing damage to neural networks, spinal cord injuries (SCI) often result in severe motor and sensory dysfunction. Functional recovery requires axonal regrowth and regeneration of neural network, processes that are quite limited in the adult central nervous system (CNS). Previous work has shown that SCI lesions contain an accumulation of activated microglia, which can have multiple pathophysiological influences. Here, we show that activated microglia inhibit axonal growth via repulsive guidance molecule a (RGMa)...
2011: PloS One
J P Frampton, M R Hynd, M L Shuler, W Shain
Two-dimensional (2D) culture systems provide useful information about many biological processes. However, some applications including tissue engineering, drug transport studies, and analysis of cell growth and dynamics are better studied using three-dimensional (3D) culture systems. 3D culture systems can potentially offer higher degrees of organization and control of cell growth environments, more physiologically relevant diffusion characteristics, and permit the formation of more extensive 3D networks of cell-cell interactions...
February 2011: Biomedical Materials
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