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astrocyte heterogeneity

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https://www.readbyqxmd.com/read/29449696/snail-regulates-bmp-and-tgf%C3%AE-pathways-to-control-the-differentiation-status-of-glioma-initiating-cells
#1
Laia Caja, Kalliopi Tzavlaki, Mahsa S Dadras, E-Jean Tan, Gad Hatem, Naga P Maturi, Anita Morén, Lotta Wik, Yukihide Watanabe, Katia Savary, Masood Kamali-Moghaddan, Lene Uhrbom, Carl-Henrik Heldin, Aristidis Moustakas
Glioblastoma multiforme is a brain malignancy characterized by high heterogeneity, invasiveness, and resistance to current therapies, attributes related to the occurrence of glioma stem cells (GSCs). Transforming growth factor β (TGFβ) promotes self-renewal and bone morphogenetic protein (BMP) induces differentiation of GSCs. BMP7 induces the transcription factor Snail to promote astrocytic differentiation in GSCs and suppress tumor growth in vivo. We demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD signaling mediators, generates a positive feedback loop of BMP signaling and transcriptionally represses the TGFB1 gene, decreasing TGFβ1 signaling activity...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29444457/brain-region-specific-responses-of-astrocytes-to-an-in-vitro-injury-and-neurotrophins
#2
Andrea Beatriz Cragnolini, Gonzalo Montenegro, Wilma J Friedman, Daniel Hugo Mascó
Astrocytes are a heterogeneous population of glial cells that react to brain insults through a process referred to as astrogliosis. Reactive astrocytes are characterized by an increase in proliferation, size, migration to the injured zone and release of a plethora of chemical mediators such as NGF and BDNF. The aim of this study was to determine whether there are brain region-associated responses of astrocytes to an injury and to the neurotrophins NGF and BDNF. We used the scratch injury model to study the closure of a wound inflicted on a monolayer of astrocytes obtained from cortex, hippocampus or striatum...
February 11, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29370841/expression-of-functional-inhibitory-neurotransmitter-transporters-glyt1-gat-1-and-gat-3-by-astrocytes-of-inferior-colliculus-and-hippocampus
#3
Elsa Ghirardini, Simon L Wadle, Vanessa Augustin, Jasmin Becker, Sina Brill, Julia Hammerich, Gerald Seifert, Jonathan Stephan
Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC) neurons receive glycinergic and GABAergic inputs, whereas inhibition in hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express neurotransmitter transporters and are expected to adapt to the local requirements regarding neurotransmitter homeostasis. Here we analyzed the expression of inhibitory neurotransmitter transporters in IC and HC astrocytes using whole-cell patch-clamp and single-cell reverse transcription-PCR...
January 25, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29358321/regulation-of-astrocyte-functions-in-multiple-sclerosis
#4
Michael A Wheeler, Francisco J Quintana
Astrocytes play complex roles in health and disease. Here, we review recent findings on molecular pathways that control astrocyte function in multiple sclerosis (MS) as well as new tools for their investigation. In particular, we describe positive and negative regulators of astrocyte-mediated pathogenesis in MS, such as sphingolipid metabolism and aryl hydrocarbon receptor signaling, respectively. In addition, we also discuss the issue of astrocyte heterogeneity and its relevance for the contribution of astrocytes to MS pathogenesis...
January 22, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29351512/physiology-of-astroglia
#5
Alexei Verkhratsky, Maiken Nedergaard
Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in development and aging. Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29350434/the-cystine-glutamate-exchanger-xct-slc7a11-is-expressed-in-significant-concentrations-in-a-subpopulation-of-astrocytes-in-the-mouse-brain
#6
Sigrid Ottestad-Hansen, Qiu Xiang Hu, Virgine Veronique Follin-Arbelet, Eduard Bentea, Hideyo Sato, Ann Massie, Yun Zhou, Niels Christian Danbolt
The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes...
January 19, 2018: Glia
https://www.readbyqxmd.com/read/29344867/immuno-laser-capture-microdissection-for-the-isolation-of-enriched-glial-populations-from-frozen-post-mortem-human-brain
#7
Julie E Simpson, Stephen B Wharton, Paul R Heath
Laser-capture microdissection (LCM) has revolutionized the isolation of defined regions and specific cell populations from human tissue. This approach used in combination with immunohistochemistry (immuno-LCM) has become a valuable method for isolating individual cell-types from a complex heterogeneous population. Here, we describe the detailed methodology required for the isolation of enriched populations of GFAP+ astrocytes, OSP+ oligodendrocytes, and CD68+ microglia from frozen post-mortem human central nervous system tissue using immuno-LCM...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29329909/the-signaling-role-for-chloride-in-the-bidirectional-communication-between-neurons-and-astrocytes
#8
REVIEW
Corinne S Wilson, Alexander A Mongin
It is well known that the electrical signaling in neuronal networks is modulated by chloride (Cl-) fluxes via the inhibitory GABAA and glycine receptors. Here, we discuss the putative contribution of Cl- fluxes and intracellular Cl- to other forms of information transfer in the CNS, namely the bidirectional communication between neurons and astrocytes. The manuscript (i) summarizes the generic functions of Cl- in cellular physiology, (ii) recaps molecular identities and properties of Cl- transporters and channels in neurons and astrocytes, and (iii) analyzes emerging studies implicating Cl- in the modulation of neuroglial communication...
January 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29317604/beta-defensin-1-aryl-hydrocarbon-receptor-and-plasma-kynurenine-in-major-depressive-disorder-metabolomics-informed-genomics
#9
Duan Liu, Balmiki Ray, Drew R Neavin, Jiabin Zhang, Arjun P Athreya, Joanna M Biernacka, William V Bobo, Daniel K Hall-Flavin, Michelle K Skime, Hongjie Zhu, Gregory D Jenkins, Anthony Batzler, Krishna R Kalari, Felix Boakye-Agyeman, Wayne R Matson, Swati S Bhasin, Taisei Mushiroda, Yusuke Nakamura, Michiaki Kubo, Ravishankar K Iyer, Liewei Wang, Mark A Frye, Rima Kaddurah-Daouk, Richard M Weinshilboum
Major depressive disorder (MDD) is a heterogeneous disease. Efforts to identify biomarkers for sub-classifying MDD and antidepressant therapy by genome-wide association studies (GWAS) alone have generally yielded disappointing results. We applied a metabolomics-informed genomic research strategy to study the contribution of genetic variation to MDD pathophysiology by assaying 31 metabolites, including compounds from the tryptophan, tyrosine, and purine pathways, in plasma samples from 290 MDD patients. Associations of metabolite concentrations with depressive symptoms were determined, followed by GWAS for selected metabolites and functional validation studies of the genes identified...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29311610/interneuron-specific-signaling-evokes-distinctive-somatostatin-mediated-responses-in-adult-cortical-astrocytes
#10
Letizia Mariotti, Gabriele Losi, Annamaria Lia, Marcello Melone, Angela Chiavegato, Marta Gómez-Gonzalo, Michele Sessolo, Serena Bovetti, Angelo Forli, Micaela Zonta, Linda Maria Requie, Iacopo Marcon, Arianna Pugliese, Cécile Viollet, Bernhard Bettler, Tommaso Fellin, Fiorenzo Conti, Giorgio Carmignoto
The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. Whether this diversity applies to other brain cells, such as the glial cells astrocytes, remains unexplored. Using optogenetics and two-photon functional imaging in the adult mouse neocortex, we here reveal that parvalbumin- and somatostatin-expressing interneurons, two key interneuron classes in the brain, differentially signal to astrocytes inducing weak and robust GABAB receptor-mediated Ca2+ elevations, respectively...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29298427/the-aging-astrocyte-transcriptome-from-multiple-regions-of-the-mouse-brain
#11
Matthew M Boisvert, Galina A Erikson, Maxim N Shokhirev, Nicola J Allen
Aging brains undergo cognitive decline, associated with decreased neuronal synapse number and function and altered metabolism. Astrocytes regulate neuronal synapse formation and function in development and adulthood, but whether these properties change during aging, contributing to neuronal dysfunction, is unknown. We addressed this by generating aged and adult astrocyte transcriptomes from multiple mouse brain regions. These data provide a comprehensive RNA-seq database of adult and aged astrocyte gene expression, available online as a resource...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29279367/cell-specific-and-region-specific-transcriptomics-in-the-multiple-sclerosis-model-focus-on-astrocytes
#12
Noriko Itoh, Yuichiro Itoh, Alessia Tassoni, Emily Ren, Max Kaito, Ai Ohno, Yan Ao, Vista Farkhondeh, Hadley Johnsonbaugh, Josh Burda, Michael V Sofroniew, Rhonda R Voskuhl
Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE)...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29247683/functional-dissection-of-astrocyte-secreted-proteins-implications-in-brain-health-and-diseases
#13
REVIEW
Mithilesh Kumar Jha, Jong-Heon Kim, Gyun Jee Song, Won-Ha Lee, In-Kyu Lee, Ho-Won Lee, Seong Soo A An, SangYun Kim, Kyoungho Suk
Astrocytes, which are homeostatic cells of the central nervous system (CNS), display remarkable heterogeneity in their morphology and function. Besides their physical and metabolic support to neurons, astrocytes modulate the blood-brain barrier, regulate CNS synaptogenesis, guide axon pathfinding, maintain brain homeostasis, affect neuronal development and plasticity, and contribute to diverse neuropathologies via secreted proteins. The identification of astrocytic proteome and secretome profiles has provided new insights into the maintenance of neuronal health and survival, the pathogenesis of brain injury, and neurodegeneration...
December 13, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/29226040/creutzfeldt-cell-rich-glioblastoma-a-diagnostic-dilemma
#14
Zain Boghani, William J Steele, Matthew D Cykowski, Leomar Y Ballester, Gavin Britz
Differentiating demyelinating conditions from neoplastic conditions can pose a significant challenge. There are a number of reports in the literature of large ring-enhancing, space-occupying lesions that were initially considered neoplastic or infectious but, on further review, were deemed demyelinating. Creutzfeldt-Peters cells (CPC) are reactive astrocytes with fragmented nuclear inclusions that are routinely seen in multiple sclerosis (MS) and generally exclude the diagnosis of glioblastoma (GB). The patient is a 78-year-old man with a history of prostate cancer, which was treated with radiation therapy, who presented with altered mental status...
October 5, 2017: Curēus
https://www.readbyqxmd.com/read/29207673/comparison-among-conventional-and-advanced-mri-18f-fdg-pet-ct-phenotype-and-genotype-in-glioblastoma
#15
Maria Consuelo Valentini, Marta Mellai, Laura Annovazzi, Antonio Melcarne, Tetyana Denysenko, Paola Cassoni, Cristina Casalone, Cristiana Maurella, Silvia Grifoni, Piercarlo Fania, Angelina Cistaro, Davide Schiffer
Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29204745/heterogeneity-and-function-of-hippocampal-macroglia
#16
REVIEW
Gerald Seifert, Christian Steinhäuser
The contribution of glial cells to normal and impaired hippocampal function is increasingly being recognized, although important questions as to the mechanisms that these cells use for their crosstalk with neurons and capillaries are still unanswered or lead to controversy. Astrocytes in the hippocampus are morphologically variable and a single cell contacts with its processes more than 100,000 synapses. They predominantly express inward rectifier K+ channels and transporters serving homeostatic function but may also release gliotransmitters to modify neuronal signaling and brain circulation...
December 4, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29168586/regional-oligodendrocytopathy-and-astrocytopathy-precede-myelin-loss-and-blood-brain-barrier-disruption-in-a-murine-model-of-osmotic-demyelination-syndrome
#17
Joanna Bouchat, Bruno Couturier, Catherine Marneffe, Fabrice Gankam-Kengne, Benoît Balau, Kathleen De Swert, Jean-Pierre Brion, Luc Poncelet, Jacques Gilloteaux, Charles Nicaise
The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination...
November 23, 2017: Glia
https://www.readbyqxmd.com/read/29143947/connexin-30-is-expressed-in-a-subtype-of-mouse-brain-pericytes
#18
Noémie Mazaré, Alice Gilbert, Anne-Cécile Boulay, Nathalie Rouach, Martine Cohen-Salmon
Pericytes are mural cells of blood microvessels which play a crucial role at the neurovascular interface of the central nervous system. They are involved in the regulation of blood-brain barrier integrity, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, and neuroinflammation, and they demonstrate stem cell activity. Morphological and molecular studies to characterize brain pericytes recently pointed out some heterogeneity in pericyte population. Nevertheless, a clear definition of pericyte subtypes is still lacking...
November 16, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29137378/trastuzumab-distribution-in-an-in-vivo-and-in-vitro-model-of-brain-metastases-of-breast-cancer
#19
Tori B Terrell-Hall, Mohamed Ismail Nounou, Fatema El-Amrawy, Jessica I G Griffith, Paul R Lockman
Background: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. Methods: We characterized the permeability of (125)I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29122627/glial-function-and-dysfunction-in-the-normal-ischemic-brain
#20
REVIEW
Shino D Magaki, Christopher K Williams, Harry V Vinters
Astrocytes are the most abundant cell type in the central nervous system (CNS). Once considered to be of fairly homogeneous phenotype throughout the brain and spinal cord, they are now understood to be heterogeneous in both structure and function. They are important in brain functions as diverse as ion and fluid balance in the interstitial space, contributing to integrity of the neurovascular unit (blood-brain barrier), neurotransmitter regulation, metabolism of energy substrates and possibly even axonal regeneration...
November 6, 2017: Neuropharmacology
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