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astrocyte heterogeneity

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https://www.readbyqxmd.com/read/28522470/three-dimensional-ca-2-imaging-advances-understanding-of-astrocyte-biology
#1
Erika Bindocci, Iaroslav Savtchouk, Nicolas Liaudet, Denise Becker, Giovanni Carriero, Andrea Volterra
Astrocyte communication is typically studied by two-dimensional calcium ion (Ca(2+)) imaging, but this method has not yielded conclusive data on the role of astrocytes in synaptic and vascular function. We developed a three-dimensional two-photon imaging approach and studied Ca(2+) dynamics in entire astrocyte volumes, including during axon-astrocyte interactions. In both awake mice and brain slices, we found that Ca(2+) activity in an individual astrocyte is scattered throughout the cell, largely compartmented between regions, preponderantly local within regions, and heterogeneously distributed regionally and locally...
May 19, 2017: Science
https://www.readbyqxmd.com/read/28516431/a-comparison-of-neuroimaging-abnormalities-in-multiple-sclerosis-major-depression-and-chronic-fatigue-syndrome-myalgic-encephalomyelitis-is-there-a-common-cause
#2
REVIEW
Gerwyn Morris, Michael Berk, Basant K Puri
There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28500556/reversing-glioma-malignancy-a-new-look-at-the-role-of-antidepressant-drugs-as-adjuvant-therapy-for-glioblastoma-multiforme
#3
Anna M Bielecka-Wajdman, Marta Lesiak, Tomasz Ludyga, Aleksander Sieroń, Ewa Obuchowicz
PURPOSE: The role of glioma stem cells (GSCs) in cancer progression is currently debated; however, it is hypothesised that this subpopulation is partially responsible for therapeutic resistance observed in glioblastoma multiforme (GBM). Recent studies have shown that the current treatments not only fail to eliminate the GSC population but even promote GSCs through reprogramming of glioma non-stem cells to stem cells. Since the standard GBM treatment often requires supplementation with adjuvant drugs such as antidepressants, their role in the regulation of the heterogeneous nature of GSCs needs evaluation...
June 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28499701/should-we-stop-saying-glia-and-neuroinflammation
#4
REVIEW
Roser Masgrau, Carmen Guaza, Richard M Ransohoff, Elena Galea
Central nervous system (CNS) therapeutics based on the theoretical framework of neuroinflammation have only barely succeeded. We argue that a problem may be the wrong use of the term 'neuroinflammation' as a distinct nosological entity when, based on recent evidence, it may not explain CNS disease pathology. Indeed, the terms 'neuroinflammation' and 'glia' could be obsolete. First, unbiased molecular profiling of CNS cell populations and individual cells reveals striking phenotypic heterogeneity in health and disease...
May 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28450076/local-energy-on-demand-are-spontaneous-astrocytic-ca-2-microdomains-the-regulatory-unit-for-astrocyte-neuron-metabolic-cooperation
#5
REVIEW
Martin Oheim, Elke Schmidt, Johannes Hirrlinger
Astrocytes are a neural cell type critically involved in maintaining brain energy homeostasis as well as signaling. Like neurons, astrocytes are a heterogeneous cell population. Cortical astrocytes show a complex morphology with a highly branched aborization and numerous fine processes ensheathing the synapses of neighboring neurons, and typically extend one process connecting to blood vessels. Recent studies employing genetically encoded fluorescent calcium (Ca(2+)) indicators have described 'spontaneous' localized Ca(2+)-transients in the astrocyte periphery that occur asynchronously, independently of signals in other parts of the cells, and that do not involve somatic Ca(2+) transients; however, neither it is known whether these Ca(2+)-microdomains occur at or near neuronal synapses nor have their molecular basis nor downstream effector(s) been identified...
April 24, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28434162/isolation-of-astrocytes-displaying-myofibroblast-properties-and-present-in-multiple-sclerosis-lesions
#6
Nicolas Vedrenne, Vincent Sarrazy, Laurence Richard, Nelly Bordeau, Serge Battu, Fabrice Billet, Alexis Desmoulière
A wide heterogeneity of lesions can affect the central nervous system (CNS). In all situations where neurons are damaged, including multiple sclerosis (MS), a common reactive astrocytosis is present. Sedimentation field-flow fractionation (SdFFF) was used to sort astrocyte subpopulations. After SdFFF elution, cells, prepared from rat newborn cortex, were cultured and analyzed by immunocytofluorescence for glial fibrillary acidic protein (GFAP) and α-smooth muscle (SM) actin (a specific marker for myofibroblasts) expression...
April 22, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28419269/dual-genotype-diffuse-low-grade-glioma-is-it-really-time-to-abandon-oligoastrocytoma-as-a-distinct-entity
#7
Valeria Barresi, Simona Lionti, Laura Valori, Giovanna Gallina, Maria Caffo, Sabrina Rossi
We report a unique case of dual-genotype oligoastrocytoma characterized by IDH2 gene mutation. The tumor was resected from the temporal lobe of a 25-year-old man. At histological examination with hematoxylin and eosin stain, it showed distinct oligodendroglial and astrocytic areas. The former retained alpha-thalassaemia/mental retardation X-linked (ATRX) immuno-expression and had absent staining for p53, while the latter had ATRX loss and p53 over-expression. Molecular analyses were separately assessed in the 2 tumor components...
April 17, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28398584/genomic-profiles-of-low-grade-murine-gliomas-evolve-during-progression-to-glioblastoma
#8
Mark Vitucci, David M Irvin, Robert S McNeill, Ralf S Schmid, Jeremy M Simon, Harshil D Dhruv, Marni B Siegel, Andrea M Werneke, Ryan E Bash, Seungchan Kim, Michael E Berens, C Ryan Miller
Background: Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear. Methods: We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease...
April 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28398520/injury-leads-to-the-appearance-of-cells-with-characteristics-of-both-microglia-and-astrocytes-in-mouse-and-human-brain
#9
Ulrika Wilhelmsson, Daniel Andersson, Yolanda de Pablo, Roy Pekny, Anders Ståhlberg, Jan Mulder, Nicholas Mitsios, Tibor Hortobágyi, Milos Pekny, Marcela Pekna
Microglia and astrocytes have been considered until now as cells with very distinct identities. Here, we assessed the heterogeneity within microglia/monocyte cell population in mouse hippocampus and determined their response to injury, by using single-cell gene expression profiling of cells isolated from uninjured and deafferented hippocampus. We found that in individual cells, microglial markers Cx3cr1, Aif1, Itgam, and Cd68 were co-expressed. Interestingly, injury led to the co-expression of the astrocyte marker Gfap in a subpopulation of Cx3cr1-expressing cells from both the injured and contralesional hippocampus...
April 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28395089/methylmalonate-induces-inflammatory-and-apoptotic-potential-a-link-to-glial-activation-and-neurological-dysfunction
#10
Patricia Gabbi, Leandro Rodrigo Ribeiro, Gutierres Jessié Martins, Alexandra Seide Cardoso, Fernanda Haupental, Fernanda Silva Rodrigues, Alencar Kolinski Machado, Juliana Sperotto Brum, M M Medeiros Frescura Duarte, Maria Rosa Chitolina Schetinger, Ivana Beatrice Mânica da Cruz, Ana Flávia Furian, Mauro Schneider Oliveira, Adair Roberto Soares Dos Santos, Luiz Fernando Freire Royes, Michele Rechia Fighera, Mayara Lutchemeyer de Freitas
Methylmalonic acid (MMA) accumulates in tissues in methylmalonic acidemia, a heterogeneous group of inherited childhood diseases characterized by neurological dysfunction, oxidative stress and neuroinflammation; it is associated with degeneration of striatal neurons and cerebral cortical atrophy. It is presently unknown, however, whether transient exposure to MMA in the neonatal period is sufficient to trigger inflammatory and apoptotic processes that lead to brain structural damage. Here, newborn mice were given a single intracerebroventricular dose of MMA at 12 hours after birth...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28379424/combination-therapy-with-potent-pi3k-and-mapk-inhibitors-overcomes-adaptive-kinome-resistance-to-single-agents-in-preclinical-models-of-glioblastoma
#11
Robert S McNeill, Demitra A Canoutas, Timothy J Stuhlmiller, Harshil D Dhruv, David M Irvin, Ryan E Bash, Steven P Angus, Laura E Herring, Jeremy M Simon, Kasey R Skinner, Juanita C Limas, Xin Chen, Ralf S Schmid, Marni B Siegel, Amanda E D Van Swearingen, Michael J Hadler, Erik P Sulman, Jann N Sarkaria, Carey K Anders, Lee M Graves, Michael E Berens, Gary L Johnson, C Ryan Miller
Background.: Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Prognosis remains poor despite multimodal therapy. Developing alternative treatments is essential. Drugs targeting kinases within the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) effectors of receptor tyrosine kinase (RTK) signaling represent promising candidates. Methods.: We previously developed a non-germline genetically engineered mouse model of GBM in which PI3K and MAPK are activated via Pten deletion and KrasG12D in immortalized astrocytes...
March 30, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28377822/translation-in-astrocyte-distal-processes-sets-molecular-heterogeneity-at-the-gliovascular-interface
#12
Anne-Cécile Boulay, Bruno Saubaméa, Nicolas Adam, Stéphanie Chasseigneaux, Noémie Mazaré, Alice Gilbert, Mathieu Bahin, Leïla Bastianelli, Corinne Blugeon, Sandrine Perrin, Juliette Pouch, Bertrand Ducos, Stéphane Le Crom, Auguste Genovesio, Fabrice Chrétien, Xavier Declèves, Jean-Louis Laplanche, Martine Cohen-Salmon
Astrocytes send out long processes that are terminated by endfeet at the vascular surface and regulate vascular functions as well as homeostasis at the vascular interface. To date, the astroglial mechanisms underlying these functions have been poorly addressed. Here we demonstrate that a subset of messenger RNAs is distributed in astrocyte endfeet. We identified, among this transcriptome, a pool of messenger RNAs bound to ribosomes, the endfeetome, that primarily encodes for secreted and membrane proteins. We detected nascent protein synthesis in astrocyte endfeet...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28370142/morphological-study-of-a-connexin-43-gfp-reporter-mouse-highlights-glial-heterogeneity-amacrine-cells-and-olfactory-ensheathing-cells
#13
Panos Theofilas, Christian Steinhäuser, Martin Theis, Amin Derouiche
Connexin 43 (Cx43) is the main astrocytic connexin and forms the basis of the glial syncytium. The morphology of connexin-expressing cells can be best studied in transgenic mouse lines expressing cytoplasmic fluorescent reporters, since immunolabeling the plaques can obscure the shapes of the individual cells. The Cx43kiECFP mouse generated by Degen et al. (FASEBJ 26:4576, 2012) expresses cytosolic ECFP and has previously been used to establish that Cx43 may not be expressed by all astrocytes within a population, and this can vary in a region-dependent way...
March 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28369648/astrocytes-are-protective-against-chlorpyrifos-developmental-neurotoxicity-in-human-pluripotent-stem-cell-derived-astrocyte-neuron-co-cultures
#14
Xian Wu, Xiangkun Yang, Anirban Majumder, Raymond Swetenburg, Forrest Goodfellow, Michael G Bartlett, Steven L Stice
Human neural progenitor (hNP) cells are capable of independent, directed differentiation into astrocytes, oligodendrocytes and neurons and thus offer a potential cell source for developmental neurotoxicity (DNT) systems. hNP-derived astrocyte-neuron co-cultured at defined ratios mimic cellular heterogeneity and interaction in the central nervous system (CNS). Cytochrome P450 enzymes are expressed at a relatively high level in astrocytes and may play a critical role in the biotransformation of endogenous or exogenous compounds, including chlorpyrifos, an organophosphate insecticide that affects the CNS...
March 24, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28356474/functional-remodeling-of-subtype-specific-markers-surrounding-implanted-neuroprostheses
#15
Joseph William Salatino, Bailey M Winter, Matthew H Drazin, Erin K Purcell
Microelectrode arrays implanted in the brain are increasingly used for the research and treatment of intractable neurological disease. However, local neuronal loss and glial encapsulation are known to interfere with effective integration and communication between implanted devices and brain tissue, where these observations are typically based on assessments of broad neuronal and astroglial markers. However, both neurons and astrocytes comprise heterogeneous cellular populations that can be further divided into subclasses based on unique functional and morphological characteristics...
March 29, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28350400/immune-involvement-in-the-pathogenesis-of-schizophrenia-a-meta-analysis-on-postmortem-brain-studies
#16
C F M G van Kesteren, H Gremmels, L D de Witte, E M Hol, A R Van Gool, P G Falkai, R S Kahn, I E C Sommer
Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories...
March 28, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#17
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28334913/tdp-43-mutations-causing-amyotrophic-lateral-sclerosis-are-associated-with-altered-expression-of-rna-binding-protein-hnrnp-k-and-affect-the-nrf2-antioxidant-pathway
#18
Diane Moujalled, Alexandra Grubman, Karla Acevedo, Shu Yang, Yazi D Ke, Donia M Moujalled, Clare Duncan, Aphrodite Caragounis, Nirma D Perera, Bradley J Turner, Mercedes Prudencio, Leonard Petrucelli, Ian Blair, Lars M Ittner, Peter J Crouch, Jeffrey R Liddell, Anthony R White
TAR DNA binding protein 43 (TDP-43) is a major disease-associated protein involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous studies found a direct association between TDP-43 and heterogeneous nuclear ribonucleoprotein K (hnRNP K). In this study, utilizing ALS patient fibroblasts harboring a TDP-43M337V mutation and NSC-34 motor neuronal cell line expressing TDP-43Q331K mutation, we show that hnRNP K expression is impaired in urea soluble extracts from mutant TDP-43 cell models...
May 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#19
Bogdan F Popescu, Josa M Frischer, Samuel M Webb, Mylyne Tham, Reginald C Adiele, Christopher A Robinson, Patrick D Fitz-Gibbon, Stephen D Weigand, Imke Metz, Susan Nehzati, Graham N George, Ingrid J Pickering, Wolfgang Brück, Simon Hametner, Hans Lassmann, Joseph E Parisi, Guo Yong, Claudia F Lucchinetti
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#20
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
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