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https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#1
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
#2
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...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#3
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
#4
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
https://www.readbyqxmd.com/read/28284341/mog-antibody-associated-demyelinating-disease-of-the-cns-a-clinical-and-pathological-study-in-chinese-han-patients
#5
Lei Zhou, Yongheng Huang, Haiqing Li, Jie Fan, Jingzi Zhangbao, Hai Yu, Yuxin Li, Jiahong Lu, Chongbo Zhao, Chuanzhen Lu, Min Wang, Chao Quan
We aim to evaluate the clinical relevance of MOG-ab in a cohort of Chinese Han adults with CNS inflammatory demyelinating diseases (IDDs). MOG-ab and AQP4-ab were examined through a fixed cell based indirect immune-fluorescence assay in 86 patients with CNS-IDDs. MOG-ab was positive in 12 patients, while AQP4-ab was positive in 31 patients; none double positives. Optic neuritis (ON) was the most frequent symptom at onset (75.0%) or during the whole disease course (83.3%) of MOG-ab associated IDDs (MOG-IDDs); 79...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28276944/imaging-and-spectroscopic-approaches-to-probe-brain-energy-metabolism-dysregulation-in-neurodegenerative-diseases
#6
Gilles Bonvento, Julien Valette, Julien Flament, Fanny Mochel, Emmanuel Brouillet
Changes in energy metabolism are generally considered to play an important role in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Whether these changes are causal or simply a part of self-defense mechanisms is a matter of debate. Furthermore, energy defects have often been discussed solely in the context of their probable neuronal origin without considering the cellular heterogeneity of the brain. Recent data point towards the existence of a tri-cellular compartmentation of brain energy metabolism between neurons, astrocytes, and oligodendrocytes, each cell type having a distinctive metabolic profile...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28251910/astrocytes-light-up-glial-heterogeneity
#7
Monica Venere
Functionally diverse subpopulations of astrocytes have correlates in the neoplastic adult brain.
March 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28243193/glial-cells-and-their-function-in-the-adult-brain-a-journey-through-the-history-of-their-ablation
#8
REVIEW
Sarah Jäkel, Leda Dimou
Glial cells, consisting of microglia, astrocytes, and oligodendrocyte lineage cells as their major components, constitute a large fraction of the mammalian brain. Originally considered as purely non-functional glue for neurons, decades of research have highlighted the importance as well as further functions of glial cells. Although many aspects of these cells are well characterized nowadays, the functions of the different glial populations in the brain under both physiological and pathological conditions remain, at least to a certain extent, unresolved...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28229909/paradoxical-inhibition-of-glycolysis-by-pioglitazone-opposes-the-mitochondriopathy-caused-by-aif-deficiency
#9
Paule Bénit, Alice Pelhaître, Elise Saunier, Sylvie Bortoli, Assetou Coulibaly, Malgorzata Rak, Manuel Schiff, Guido Kroemer, Massimo Zeviani, Pierre Rustin
Mice with the hypomorphic AIF-Harlequin mutation exhibit a highly heterogeneous mitochondriopathy that mostly affects respiratory chain complex I, causing a cerebral pathology that resembles that found in patients with AIF loss-of-function mutations. Here we describe that the antidiabetic drug pioglitazone (PIO) can improve the phenotype of a mouse Harlequin (Hq) subgroup, presumably due to an inhibition of glycolysis that causes an increase in blood glucose levels. This glycolysis-inhibitory PIO effect was observed in cultured astrocytes from Hq mice, as well as in human skin fibroblasts from patients with AIF mutation...
February 16, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28208745/astrocytic-pathological-calcium-homeostasis-and-impaired-vesicle-trafficking-in-neurodegeneration
#10
REVIEW
Nina Vardjan, Alexej Verkhratsky, Robert Zorec
Although the central nervous system (CNS) consists of highly heterogeneous populations of neurones and glial cells, clustered into diverse anatomical regions with specific functions, there are some conditions, including alertness, awareness and attention that require simultaneous, coordinated and spatially homogeneous activity within a large area of the brain. During such events, the brain, representing only about two percent of body mass, but consuming one fifth of body glucose at rest, needs additional energy to be produced...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28166219/identification-of-diverse-astrocyte-populations-and-their-malignant-analogs
#11
Chia-Ching John Lin, Kwanha Yu, Asante Hatcher, Teng-Wei Huang, Hyun Kyoung Lee, Jeffrey Carlson, Matthew C Weston, Fengju Chen, Yiqun Zhang, Wenyi Zhu, Carrie A Mohila, Nabil Ahmed, Akash J Patel, Benjamin R Arenkiel, Jeffrey L Noebels, Chad J Creighton, Benjamin Deneen
Astrocytes are the most abundant cell type in the brain, where they perform a wide array of functions, yet the nature of their cellular heterogeneity and how it oversees these diverse roles remains shrouded in mystery. Using an intersectional fluorescence-activated cell sorting-based strategy, we identified five distinct astrocyte subpopulations present across three brain regions that show extensive molecular diversity. Application of this molecular insight toward function revealed that these populations differentially support synaptogenesis between neurons...
March 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28153089/genome-editing-reveals-glioblastoma-addiction-to-microrna-10b
#12
Rachid El Fatimy, Shruthi Subramanian, Erik J Uhlmann, Anna M Krichevsky
Glioblastoma (GBM) brain tumor remains among the most lethal and incurable human diseases. Oncogenic microRNA-10b (miR-10b) is strongly and universally upregulated in GBM, and its inhibition by antisense oligonucleotides (ASOs) reduces the growth of heterogeneous glioma cells; therefore, miR-10b represents a unique therapeutic target for GBM. Here we explored the effects of miR-10b gene editing on GBM. Using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system, we investigated effects of miR-10b gene editing on the growth of cultured human glioma cells, tumor-initiating stem-like cells, and mouse GBM xenografts, as well as the oncogene-induced transformation of normal astrocytes...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28126746/genetically-defined-oligodendroglioma-is-characterized-by-indistinct-tumor-borders-at-mri
#13
D R Johnson, F E Diehn, C Giannini, R B Jenkins, S M Jenkins, I F Parney, T J Kaufmann
BACKGROUND AND PURPOSE: In 2016, the World Health Organization revised the brain tumor classification, making IDH mutation and 1p/19q codeletion the defining features of oligodendroglioma. To determine whether imaging characteristics previously associated with oligodendroglial tumors are still applicable, we evaluated the MR imaging features of genetically defined oligodendrogliomas. MATERIALS AND METHODS: One hundred forty-eight adult patients with untreated World Health Organization grade II and III infiltrating gliomas with histologic oligodendroglial morphology, known 1p/19q status, and at least 1 preoperative MR imaging were retrospectively identified...
January 26, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28099854/single-cell-transcriptomic-analysis-defines-heterogeneity-and-transcriptional-dynamics-in-the-adult-neural-stem-cell-lineage
#14
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
#15
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
#16
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
#17
REVIEW
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
#18
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
#19
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
#20
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
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