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astrocyte heterogeneity

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https://www.readbyqxmd.com/read/28821665/molecular-and-functional-properties-of-regional-astrocytes-in-the-adult-brain
#1
Lydie Morel, Ming Sum R Chiang, Haruki Higashimori, Temitope Shoneye, Lakshmanan K Iyer, Julia Yelick, Albert Tai, Yongjie Yang
The molecular signature and functional properties of astroglial subtypes in the adult central nervous system (CNS) remain largely undefined. By employing translational ribosome affinity purification (TRAP) followed by RNA-seq, we profiled astroglial ribosome-associated (presumably translating) mRNAs in major cortical and subcortical brain regions (cortex, hippocampus, caudate putamen, nucleus accumbens, thalamus, and hypothalamus) of BAC aldh1l1-TRAP mice (both sexes). We found that the expression of astroglial translating mRNAs closely follows the dorsoventral axis especially from cortex/hippocampus to thalamus/hypothalamus posteriorly...
August 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28806136/harnessing-olig2-function-in-tumorigenicity-and-plasticity-to-target-malignant-gliomas
#2
Jennifer Kosty, Fanghui Lu, Robert Kupp, Shwetal Mehta, Q Richard Lu
Glioblastoma (GBM) is the most prevalent and malignant brain tumor, displaying notorious resistance to conventional therapy, partially due to molecular and genetic heterogeneity. Understanding the mechanisms for gliomagenesis, tumor stem/progenitor cell propagation and phenotypic diversity is critical for devising effective and targeted therapy for this lethal disease. The basic helix-loop-helix transcription factor OLIG2, which is universally expressed in gliomas, has emerged as an important player in GBM cell reprogramming, genotoxic resistance, and tumor phenotype plasticity...
August 14, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28778090/trastuzumab-distribution-in-an-in-vivo-and-in-vitro-model-of-brain-metastases-of-breast-cancer
#3
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 125I-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...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28775382/divergent-co-transcriptomes-of-different-host-cells-infected-with-toxoplasma-gondii-reveal-cell-type-specific-host-parasite-interactions
#4
Izabela J Swierzy, Ulrike Händel, Alexander Kaever, Michael Jarek, Maren Scharfe, Dirk Schlüter, Carsten G K Lüder
The apicomplexan parasite Toxoplasma gondii infects various cell types in avian and mammalian hosts including humans. Infection of immunocompetent hosts is mostly asymptomatic or benign, but leads to development of largely dormant bradyzoites that persist predominantly within neurons and muscle cells. Here we have analyzed the impact of the host cell type on the co-transcriptomes of host and parasite using high-throughput RNA sequencing. Murine cortical neurons and astrocytes, skeletal muscle cells (SkMCs) and fibroblasts differed by more than 16,200 differentially expressed genes (DEGs) before and after infection with T...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28748452/single-cell-transcriptomics-reveals-gene-signatures-and-alterations-associated-with-aging-in-distinct-neural-stem-progenitor-cell-subpopulations
#5
Zhanping Shi, Yanan Geng, Jiping Liu, Huina Zhang, Liqiang Zhou, Quan Lin, Juehua Yu, Kunshan Zhang, Jie Liu, Xinpei Gao, Chunxue Zhang, Yinan Yao, Chong Zhang, Yi E Sun
Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside...
July 26, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28740449/genetic-factors-affecting-intraoperative-5-aminolevulinic-acid-induced-fluorescence-of-diffuse-gliomas
#6
Kiyotaka Saito, Toshinori Hirai, Hideo Takeshima, Yoshihito Kadota, Shinji Yamashita, Asya Ivanova, Kiyotaka Yokogami
BACKGROUND: In patients operated for malignant glioma, 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance is useful. However, we occasionally experience instances of non-visible fluorescence despite a histopathological diagnosis of high-grade glioma. We sought to identify factors that influence the intraoperative visualization of gliomas by their 5-ALA-induced fluorescence. PATIENTS AND METHODS: We reviewed data from 60 patients with astrocytic or oligodendroglial tumors who underwent tumor removal under 5-ALA-induced fluorescence guidance between January 2014 and December 2015...
June 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28728846/the-effects-of-type-i-interferon-on-glioblastoma-cancer-stem-cells
#7
Ziyun Du, Chun Cai, Michelle Sims, Frederick A Boop, Andrew M Davidoff, Lawrence M Pfeffer
Glioblastomas (GBMs) are highly invasive brain tumors that are extremely deadly. The highly aggressive nature of GBM as well as its heterogeneity at the molecular and cellular levels has been attributed to a rare subpopulation of GBM stem-like cells (GSCs). Interferons (IFNs) are a family of endogenous antiviral proteins that have anticancer activity in vitro, and have been used clinically to treat GBM. IFN inhibits the proliferation of various established GBM cell lines, but the effects of IFNs on GSCs remain relatively unknown...
July 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28725186/foxb1-regulates-negatively-the-proliferation-of-oligodendrocyte-progenitors
#8
Yuanfeng Zhang, Elti Hoxha, Tianyu Zhao, Xunlei Zhou, Gonzalo Alvarez-Bolado
Oligodendrocyte precursor cells (OPC), neurons and astrocytes share a neural progenitor cell (NPC) in the early ventricular zone (VZ) of the embryonic neuroepithelium. Both switch to produce either of the three cell types and the generation of the right number of them undergo complex genetic regulation. The components of these regulatory cascades vary between brain regions giving rise to the unique morphological and functional heterogeneity of this organ. Forkhead b1 (Foxb1) is a transcription factor gene expressed by NPCs in specific regions of the embryonic neuroepithelium...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28700615/astrocyte-heterogeneity-across-the-brain-and-spinal-cord-occurs-developmentally-in-adulthood-and-in-response-to-demyelination
#9
Hyesook Yoon, Grant Walters, Alex R Paulsen, Isobel A Scarisbrick
Astrocytes have emerged as essential regulators of function and response to injury in the brain and spinal cord, yet very little is known about regional differences that exist. Here we compare the expression of key astroglial markers (glial fibrillary acidic protein (GFAP) and Aldehyde Dehydrogenase-1 Family Member L1 (ALDH1L1)) across these disparate poles of the neuraxis, tracking their expression developmentally and in the context of demyelination. In addition, we document changes in the astrocyte regulatory cytokine interleukin 6 (IL-6), and its signaling partner signal transducer and activator of transcription 3 (STAT3), in vivo and in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28700589/ank1-is-up-regulated-in-laser-captured-microglia-in-alzheimer-s-brain-the-importance-of-addressing-cellular-heterogeneity
#10
Diego Mastroeni, Shobana Sekar, Jennifer Nolz, Elaine Delvaux, Katie Lunnon, Jonathan Mill, Winnie S Liang, Paul D Coleman
Recent epigenetic association studies have identified a new gene, ANK1, in the pathogenesis of Alzheimer's disease (AD). Although strong associations were observed, brain homogenates were used to generate the data, introducing complications because of the range of cell types analyzed. In order to address the issue of cellular heterogeneity in homogenate samples we isolated microglial, astrocytes and neurons by laser capture microdissection from CA1 of hippocampus in the same individuals with a clinical and pathological diagnosis of AD and matched control cases...
2017: PloS One
https://www.readbyqxmd.com/read/28676398/spatiotemporal-control-of-mitochondrial-network-dynamics-in-astroglial-cells
#11
Jana Göbel, Elisa Motori, Matteo Bergami
Mitochondria are increasingly recognized for playing important roles in regulating the evolving metabolic state of mammalian cells. This is particularly true for nerve cells, as dysregulation of mitochondrial dynamics are invariably associated with a number of neuropathies. Accumulating evidence now reveals that changes in mitochondrial dynamics and structure may play equally important roles also in the cell biology of astroglial cells. Astroglial cells display a significant heterogeneity in their morphology and specialized functions across the different brain regions, however besides fundamental differences they seem to share a surprisingly complex meshwork of mitochondria, which is highly suggestive of tightly regulated mechanisms that contribute to maintain this unique architecture...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28670569/molecular-and-microenvironmental-determinants-of-glioma-stem-like-cell-survival-and-invasion
#12
REVIEW
Alison Roos, Zonghui Ding, Joseph C Loftus, Nhan L Tran
Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults with a 5-year survival rate of 5% despite intensive research efforts. The poor prognosis is due, in part, to aggressive invasion into the surrounding brain parenchyma. Invasion is a complex process mediated by cell-intrinsic pathways, extrinsic microenvironmental cues, and biophysical cues from the peritumoral stromal matrix. Recent data have attributed GBM invasion to the glioma stem-like cell (GSC) subpopulation. GSCs are slowly dividing, highly invasive, therapy resistant, and are considered to give rise to tumor recurrence...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28665546/astroglial-vesicular-network-evolutionary-trends-physiology-and-pathophysiology
#13
REVIEW
R Zorec, V Parpura, A Verkhratsky
Intracellular organelles, including secretory vesicles, emerged when eukaryotic cells evolved some 3 billion years ago. The primordial organelles that evolved in Archaea were similar to endolysosomes, which developed, arguably, for specific metabolic tasks, including uptake, metabolic processing, storage and disposal of molecules. In comparison with prokaryotes, cell volume of eukaryotes increased by several orders of magnitude and vesicle traffic emerged to allow for communication between distant intracellular locations...
June 30, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28585380/astrocytes-in-a-dish-using-pluripotent-stem-cells-to-model-neurodegenerative-and-neurodevelopmental-disorders
#14
Lucy A Crompton, Oscar Cordero-Llana, Maeve A Caldwell
Neuroscience and Neurobiology have historically been neuron biased, yet up to 40% of the cells in the brain are astrocytes. These cells are heterogeneous and regionally diverse but universally essential for brain homeostasis. Astrocytes regulate synaptic transmission as part of the tripartite synapse, provide metabolic and neurotrophic support, recycle neurotransmitters, modulate blood flow and brain blood barrier permeability and are implicated in the mechanisms of neurodegeneration. Using pluripotent stem cells (PSC), it is now possible to study regionalised human astrocytes in a dish and to model their contribution to neurodevelopmental and neurodegenerative disorders...
July 2017: Brain Pathology
https://www.readbyqxmd.com/read/28581635/targeted-unlabeled-multiple-reaction-monitoring-analysis-of-cell-markers-for-the-study-of-sample-heterogeneity-in-isolated-rat-brain-cortical-microvessels
#15
David Gomez-Zepeda, Catarina Chaves, Méryam Taghi, Philippe Sergent, Wang-Qing Liu, Cérina Chhuon, Michel Vidal, Martin Picard, Elizabeth Thioulouse, Isabelle Broutin, Ida-Chiara Guerrera, Jean-Michel Scherrmann, Yannick Parmentier, Xavier Decleves, Marie-Claude Menet
Liquid chromatography coupled to tandem mass spectrometry-based targeted absolute protein quantification (in fmol of the analyte protein per μg of total protein) is employed for the molecular characterization of the blood-brain barrier using isolated brain microvessels. Nevertheless, the heterogeneity of the sample regarding the levels of different cells co-isolated within the microvessels and bovine serum albumin (BSA) contamination (from buffers) are not always evaluated. We developed an unlabeled targeted liquid chromatography coupled to tandem mass spectrometry method to survey the levels of endothelial cells (ECs), astrocytes, and pericytes, as well as BSA contaminant in rat cortical microvessels...
June 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28552414/qki6b-mrna-levels-are-upregulated-in-schizophrenia-and-predict-gfap-expression
#16
B Farnsworth, K J Radomska, B Zimmermann, P Kettunen, E Jazin, L S Emilsson
Schizophrenia is a highly heritable disorder with a heterogeneous symptomatology. Research increasingly indicates the importance of the crucial and often overlooked glial perturbations within schizophrenia. Within this study, we examined an isoform of quaking (a gene encoding an RNA-binding protein that is exclusively expressed in glial cells), known as QKI6B, and a prototypical astrocyte marker, glial fibrillary acidic protein (GFAP), postulated to be under the regulation of QKI. The expression levels of these genes were quantified across post-mortem brain samples from 55 schizophrenic individuals, and 55 healthy controls, using real-time PCR...
May 25, 2017: Brain Research
https://www.readbyqxmd.com/read/28522470/three-dimensional-ca-2-imaging-advances-understanding-of-astrocyte-biology
#17
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
#18
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
#19
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
#20
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
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