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microglia process outgrowth

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...
2015: 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
Dustin J Hines, Rochelle M Hines, Sean J Mulligan, Brian A Macvicar
Microglia cells exhibit two forms of motility, constant movement of filopodia probing surrounding brain tissue, and outgrowth of larger processes in response to nearby damage. The mechanisms and functions of filopodia sensing and process outgrowth are not well characterized but are likely critical for normal immune function in the brain. Using two photon laser scanning microscopy we investigated microglia process outgrowth in response to damage, and explored the relationship between process outgrowth and filopodia movement...
November 15, 2009: Glia
Lv Li, Jia Lu, Samuel Sam Wah Tay, Shabbir M Moochhala, Bei Ping He
Opposing functions of activated microglia, namely neuroprotection or neurotrophy versus neurodestruction or neurotoxicity, have been observed in a number of experimental models of neurotrauma and neurodegenerative diseases. However, the mechanism(s) involved in the determination of which function activated microglia execute under a given set of conditions still remains to be elucidated. Our current in vitro study has revealed that a neuroprotective/neurotrophic or a neurodestructive/neurotoxic microglial function may be configured by the equilibrium among various microglial factors released into the microenvironment...
July 23, 2007: Brain Research
Michelle G Hamel, Joanne Mayer, Paul E Gottschall
Brevican, a proteoglycan of the lectican family, inhibits neurite outgrowth and may also stabilize synapses. Little is known about its expression or function in vitro. This study seeks to determine whether a brevican-containing matrix is present in neural cultures, and if so, how the production of brevican may be modulated. To accomplish this, the content of brevican and its proteolytic fragments were measured in primary cultures of neurons, astrocytes and microglia after treatment with cytokines. These experiments revealed that astrocytes and neurons express several isoforms of brevican, whereas microglia do not produce this proteoglycan...
June 2005: Journal of Neurochemistry
Yumiko Abe, Hiroshi Nakamura, Osamu Yoshino, Takeshi Oya, Tomoatsu Kimura
Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin. It plays an important role in the nervous system, including the processes of neuronal migration, neurite outgrowth, and neuronal plasticity. tPA has also been suggested to have a role in several neuropathological conditions, such as cerebral ischemia, seizures, and demyelinating diseases. To investigate the role of tPA in spinal cord injury, wild-type mice and mice with homozygous tPA deficiency (tPA(-/-) mice) were subjected to spinal cord contusion and the differences of hindlimb function, electrophysiological changes, and histopathological changes were assessed for 6 weeks...
January 2003: Journal of Neurotrauma
Stella E Tsirka
The tissue plasminogen activator (tPA)/plasmin proteolytic system has been implicated in both physiological and pathological processes in the mammalian brain. The physiological roles include facilitating neurite outgrowth and pathfinding. The pathological role involves mediating a critical step in the progression of excitotoxin-induced neurodegeneration. Mechanistically, tPA appears to function through two pathways. The first pathway proceeds via its well established ability to convert plasminogen into plasmin...
April 2002: Biochemical Society Transactions
Harald Neumann, Rudiger Schweigreiter, Toshihide Yamashita, Katja Rosenkranz, Hartmut Wekerle, Yves-Alain Barde
In response to injury and inflammation of the CNS, brain cells including microglia and astrocytes secrete tumor necrosis factor-alpha (TNF). This pro-inflammatory cytokine has been implicated in both neuronal cell death and survival. We now provide evidence that TNF affects the formation of neurites. Neurons cultured on astrocytic glial cells exhibited reduced outgrowth and branching of neurites after addition of recombinant TNF or prestimulation of glial cells to secrete TNF. This effect was absent in neurons of TNF receptor-deficient mice cultured on prestimulated glia of wild-type mice and was reverted by blocking TNF with soluble TNF receptor IgG fusion protein...
February 1, 2002: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
L C Park, H Zhang, G E Gibson
Thiamine deficiency (TD) is a model of chronic impairment of oxidative metabolism that leads to neurodegeneration. TD induces oxidative stress and death in neurons, but does not kill astrocytes, microglia or brain endothelial cells. TD primary hippocampal neurons were either cultured alone, or co-cultured with primary astrocytes or microglia. After 7 days of TD, 50% of the neurons died, and the processes of many of the surviving neurons were severely truncated. When TD neurons were co-cultured with astrocytes or microglia, neurons did not die nor show decreased neurite outgrowth...
December 2001: Mechanisms of Ageing and Development
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