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astrocyte heterogeneity

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https://www.readbyqxmd.com/read/28099854/single-cell-transcriptomic-analysis-defines-heterogeneity-and-transcriptional-dynamics-in-the-adult-neural-stem-cell-lineage
#1
Ben W Dulken, Dena S Leeman, Stéphane C Boutet, Katja Hebestreit, Anne Brunet
Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Here, we use single-cell RNA sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. We find that cells in the NSC lineage exist on a continuum through the processes of activation and differentiation. Interestingly, rare intermediate states with distinct molecular profiles can be identified and experimentally validated, and our analysis identifies putative surface markers and key intracellular regulators for these subpopulations of NSCs...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#2
Deborah Rotoli, Natalia Dolores Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28076568/immunohistochemical-analysis-of-retinoblastoma-cell-phenotype-using-neuronal-and-glial-cell-markers
#3
María Eugenia Orellana, Rubens Belfort, Emilia Antecka, Miguel Noel Burnier
Purpose: The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Methods: Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2), the mature neuronal cell marker microtubule-associated protein 2 (MAP2), and the mature glial cell marker glial fibrillary acidic protein (GFAP)...
November 2016: Arquivos Brasileiros de Oftalmologia
https://www.readbyqxmd.com/read/28069435/astrocytes-and-presynaptic-plasticity-in-the-striatum-evidence-and-unanswered-questions
#4
Anton Dvorzhak, Igor Melnick, Rosemarie Grantyn
One of the main functions of astrocytes is to ensure glutamate homeostasis by glutamate uptake and glutamine synthesis. However, during the past ten years it has become clear that astrocytes may also induce changes in synaptic glutamate release when respective pathways must cope with the consequences of brain damage or other alterations in their functional requirements. The loss of glutamatergic synapses in Parkinson's and Huntington's disease is likely to associate with a continuous redistribution of presynaptic activity within the pool of surviving synapses, and astrocytes may have a role in the maintenance of independent control at individual glutamate release sites...
January 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28050794/heterogeneity-in-synaptogenic-profile-of-astrocytes-from-different-brain-regions
#5
Andrea Schmidt Buosi, Isadora Matias, Ana Paula Bergamo Araujo, Carolina Batista, Flávia Carvalho Alcantara Gomes
Astrocytes, the most abundant glial cells in the central nervous system (CNS), comprise a heterogeneous population of cells. However, how this heterogeneity impacts their function within brain homeostasis and response to injury and disease is still largely unknown. Recently, astrocytes have been recognized as important regulators of synapse formation and maturation. Here, we analyzed the synaptogenic property of astrocytes from different regions of the CNS. The effect of conditioned medium derived from astrocytes (astrocyte-conditioned medium (ACM)) from cerebral cortex, hippocampus, midbrain and cerebellum, in synapse formation, was evaluated...
January 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28040794/native-oligodendrocytes-in-astrocytomas-might-inhibit-tumor-proliferation-by-wif1-expression
#6
Martin Asslaber, Silvia Schauer, Margit Gogg-Kamerer, Eva Bernhart, Franz Quehenberger, Johannes Haybaeck
Malignant astrocytoma remains incurable and rapidly fatal despite multimodal therapy. In particular, accelerated tumor cell heterogeneity often overcomes therapeutic effects of molecular protein targeting. This study aimed at identifying a gene with therapeutic potential that was consistently downregulated with astrocytoma progression. Analysis of the "Rembrandt" gene expression data revealed Wnt inhibitory factor 1 (WIF1) gene as the most promising candidate with tumor suppressor function. Consequently, 288 randomly selected tissue regions of astrocytoma specimens were investigated immunohistochemically with the aid of image analysis...
December 31, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27998013/neuroprotective-and-ameliorating-impacts-of-omega-3-against-aspartame-induced-neuronal-and-astrocytic-degeneration
#7
Eyad M T Ali, Hany M A Sonpol
Aspartame (ASP) is one of the commonest artificial sweetener used all over the world and considered as an extremely risky compound and raises a lot of controversy. Therefore, this study was designed to investigate cellular damage of the anterior horn cells in the spinal cord of albino male rats and the possibility of hindering these changes by using omega-3 (OM3).Thirty seven adult male albino rats were divided into three groups: Control, ASP-treated and ASP+OM3-treated groups. Spinal cord sections were prepared and stained with Hx&E, caspase-3 and GFAP immunostaining...
December 20, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/27995945/the-developing-landscape-of-diagnostic-and-prognostic-biomarkers-for-spinal-cord-injury-in-cerebrospinal-fluid-and-blood
#8
REVIEW
C H Hulme, S J Brown, H R Fuller, J Riddell, A Osman, J Chowdhury, N Kumar, W E Johnson, K T Wright
STUDY DESIGN: Review study. OBJECTIVES: The identification of prognostic biomarkers of spinal cord injury (SCI) will help to assign SCI patients to the correct treatment and rehabilitation regimes. Further, the detection of biomarkers that predict permanent neurological outcome would aid in appropriate recruitment of patients into clinical trials. The objective of this review is to evaluate the current state-of-play in this developing field. SETTING: Studies from multiple countries were included...
December 20, 2016: Spinal Cord
https://www.readbyqxmd.com/read/27959385/microtubule-actin-cross-linking-factor-1-a-novel-target-in-glioblastoma
#9
Najlaa Afghani, Toral Mehta, Jialiang Wang, Nan Tang, Omar Skalli, Quincy A Quick
Genetic heterogeneity is recognized as a major contributing factor of glioblastoma resistance to clinical treatment modalities and consequently low overall survival rates. This genetic diversity results in variations in protein expression, both intratumorally and between individual glioblastoma patients. In this regard, the spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1), was examined in glioblastoma. An expression analysis of MACF1 in various types of brain tumor tissue revealed that MACF1 was predominately present in grade III-IV astroctyomas and grade IV glioblastoma, but not in normal brain tissue, normal human astrocytes and lower grade brain tumors...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27911416/the-indirect-neuron-astrocyte-coculture-assay-an-in-vitro-set-up-for-the-detailed-investigation-of-neuron-glia-interactions
#10
Christine Gottschling, Egor Dzyubenko, Maren Geissler, Andreas Faissner
Proper neuronal development and function is the prerequisite of the developing and the adult brain. However, the mechanisms underlying the highly controlled formation and maintenance of complex neuronal networks are not completely understood thus far. The open questions concerning neurons in health and disease are diverse and reaching from understanding the basic development to investigating human related pathologies, e.g., Alzheimer's disease and Schizophrenia. The most detailed analysis of neurons can be performed in vitro...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27904142/functional-diversity-of-astrocytes-in-neural-circuit-regulation
#11
Lucile Ben Haim, David H Rowitch
Although it is well established that all brain regions contain various neuronal subtypes with different functions, astrocytes have traditionally been thought to be homogenous. However, recent evidence has shown that astrocytes in the mammalian CNS display distinct inter- and intra-regional features, as well as functional diversity. In the CNS, astrocyte processes fill the local environment in non-overlapping domains. Therefore, a potential advantage of region-specified astrocytes might be their capacity to regulate local development or optimize local neural circuit function...
January 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/27853976/tapered-tip-capillary-electrophoresis-nano-electrospray-ionization-mass-spectrometry-for-ultrasensitive-proteomics-the-mouse-cortex
#12
Sam B Choi, Marta Zamarbide, M Chiara Manzini, Peter Nemes
Ultrasensitive characterization of the proteome raises the potential to understand how differential gene expression orchestrates cell heterogeneity in the brain. Here, we report a microanalytical capillary electrophoresis nano-flow electrospray ionization (CE-nanoESI) interface for mass spectrometry to enable the measurement of limited amounts of proteins in the mouse cortex. Our design integrates a custom-built CE system to a tapered-tip metal emitter in a co-axial sheath-flow configuration. This interface can be constructed in <15 min using readily available components, facilitating broad adaptation...
November 16, 2016: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/27801899/analysis-of-induced-pluripotent-stem-cells-carrying-22q11-2-deletion
#13
M Toyoshima, W Akamatsu, Y Okada, T Ohnishi, S Balan, Y Hisano, Y Iwayama, T Toyota, T Matsumoto, N Itasaka, S Sugiyama, M Tanaka, M Yano, B Dean, H Okano, T Yoshikawa
Given the complexity and heterogeneity of the genomic architecture underlying schizophrenia, molecular analyses of these patients with defined and large effect-size genomic defects could provide valuable clues. We established human-induced pluripotent stem cells from two schizophrenia patients with the 22q11.2 deletion (two cell lines from each subject, total of four cell lines) and three controls (total of four cell lines). Neurosphere size, neural differentiation efficiency, neurite outgrowth, cellular migration and the neurogenic-to-gliogenic competence ratio were significantly reduced in patient-derived cells...
November 1, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27796748/relationship-between-obesity-alzheimer-s-disease-and-parkinson-s-disease-an-astrocentric-view
#14
REVIEW
Cynthia Alexandra Martin-Jiménez, Diana Milena Gaitán-Vaca, Valentina Echeverria, Janneth González, George E Barreto
Obesity is considered one of the greatest risk to human health and is associated with several factors including genetic components, diet, and physical inactivity. Recently, the relationship between obesity and numerous progressive and aging-related neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) have been observed. Thus, the involvement of the most abundant and heterogeneous group of glial cells in neurodegenerative diseases, the astrocytes, is caused by a combination of the failure on their normal homeostatic functions and the increase of toxic metabolites upon pathological event...
October 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27790055/optogenetic-and-chemogenetic-approaches-for-studying-astrocytes-and-gliotransmitters
#15
REVIEW
Juwon Bang, Hak Yeong Kim, Hyosang Lee
The brain consists of heterogeneous populations of neuronal and non-neuronal cells. The revelation of their connections and interactions is fundamental to understanding normal brain functions as well as abnormal changes in pathological conditions. Optogenetics and chemogenetics have been developed to allow functional manipulations both in vitro and in vivo to examine causal relationships between cellular changes and functional outcomes. These techniques are based on genetically encoded effector molecules that respond exclusively to exogenous stimuli, such as a certain wavelength of light or a synthetic ligand...
October 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/27779684/microfluidic-profiling-of-apoptosis-related-genes-after-treatment-with-bh3-mimetic-agents-in-astrocyte-and-glioblastoma-cell-lines
#16
Eva Vidomanova, Peter Racay, Ivana Pilchova, Erika Halasova, Jozef Hatok
Glioblastoma (GB) is the most frequent and biologically the most aggressive primary brain tumor in adults. Standard treatment for newly diagnosed GB consists of surgical resection, radiotherapy and chemotherapy. Resistance to therapy is a major obstacle, even with optimal treatment with a survival median of only 12-15 months. The heterogeneity and treatment response of GB makes this tumor type a challenging area of research. The aim of our study was to study the response of normal human astrocyte (HA) and human GB (T98G) cell lines to apoptosis inhibitors in vitro...
December 2016: Oncology Reports
https://www.readbyqxmd.com/read/27714685/microglia-function-in-the-normal-brain
#17
Rommy von Bernhardi, Florencia Heredia, Nicole Salgado, Paola Muñoz
The activation of microglia has been recognized for over a century by their morphological changes. Long slender microglia acquire a short sturdy ramified shape when activated. During the past 20 years, microglia have been accepted as an essential cellular component for understanding the pathogenic mechanism of many brain diseases, including neurodegenerative diseases. More recently, functional studies and imaging in mouse models indicate that microglia are active in the healthy central nervous system. It has become evident that microglia release several signal molecules that play key roles in the crosstalk among brain cells, i...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27647730/a-mosaic-world-puzzles-revealed-by-adult-neural-stem-cell-heterogeneity
#18
REVIEW
Zayna Chaker, Paolo Codega, Fiona Doetsch
Neural stem cells (NSCs) reside in specialized niches in the adult mammalian brain. The ventricular-subventricular zone (V-SVZ), adjacent to the lateral ventricles, gives rise to olfactory bulb (OB) neurons, and some astrocytes and oligodendrocytes throughout life. In vitro assays have been widely used to retrospectively identify NSCs. However, cells that behave as stem cells in vitro do not reflect the identity, diversity, and behavior of NSCs in vivo. Novel tools including fluorescence activated cell sorting, lineage-tracing, and clonal analysis have uncovered multiple layers of adult V-SVZ NSC heterogeneity, including proliferation state and regional identity...
November 2016: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/27628292/astroglial-vesicular-trafficking-in-neurodegenerative-diseases
#19
Robert Zorec, Vladimir Parpura, Alexei Verkhratsky
The neocortex represents one of the largest estates of the human brain. This structure comprises ~30-40 billions of neurones and even more of non-neuronal cells. Astrocytes, highly heterogeneous homoeostatic glial cells, are fundamental for housekeeping of the brain and contribute to information processing in neuronal networks. Gray matter astrocytes tightly enwrap synapses, contact blood vessels and, naturally, are also in contact with the extracellular space, where convection of fluid takes place. Thus astrocytes receive signals from several distinct extracellular domains and can get excited by numerous mechanisms, which regulate cytosolic concentration of second messengers, such as Ca(2+) and cAMP...
September 14, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27606318/cell-type-specific-effects-of-mutant-disc1-a-proteomics-study
#20
Meng Xia, Jantine A C Broek, Yan Jouroukhin, Jeannine Schoenfelder, Sofya Abazyan, Hanna Jaaro-Peled, Akira Sawa, Sabine Bahn, Mikhail Pletnikov
Despite the recent progress in psychiatric genetics, very few studies have focused on genetic risk factors in glial cells that, compared to neurons, can manifest different molecular pathologies underlying psychiatric disorders. In order to address this issue, we studied the effects of mutant disrupted in schizophrenia 1 (DISC1), a genetic risk factor for schizophrenia, in cultured primary neurons and astrocytes using an unbiased mass spectrometry-based proteomic approach. We found that selective expression of mutant DISC1 in neurons affects a wide variety of proteins predominantly involved in neuronal development (e...
May 2016: Molecular Neuropsychiatry
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