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astrocyte heterogeneity

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
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
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
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
Marco Magistri, Nathalie Khoury, Emilia Maria Cristina Mazza, Dmitry Velmeshev, Jae K Lee, Silvio Bicciato, Pantelis Tsoulfas, Mohammad Ali Faghihi
Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of specific molecular markers and by the difficulties associated with purifying and culturing astrocytes from adult human brains. Human neural progenitor cells (NPCs) with self-renewal and multipotent properties represent an appealing model system to gain insight into the developmental genetics and function of human astrocytes, but a comprehensive molecular characterization that confirms the validity of this cellular system is still missing...
August 26, 2016: European Journal of Neuroscience
Giulia Tyzack, Andras Lakatos, Rickie Patani
Astrocytes abound in the human central nervous system (CNS) and play a multitude of indispensable roles in neuronal homeostasis and regulation of synaptic plasticity. While traditionally considered to be merely ancillary supportive cells, their complex yet fundamental relevance to brain physiology and pathology have only become apparent in recent times. Beyond their myriad canonical functions, previously unrecognised region-specific functional heterogeneity of astrocytes is emerging as an important attribute and challenges the traditional perspective of CNS-wide astrocyte homogeneity...
2016: Current Stem Cell Reports
Eva Lasič, Fabiana Galland, Nina Vardjan, Jernej Šribar, Igor Križaj, Marina Concli Leite, Robert Zorec, Matjaž Stenovec
Astrocytes, the most heterogeneous glial cells in the central nervous system, contribute to brain homeostasis, by regulating a myriad of functions, including the clearance of extracellular debris. When cells are damaged, cytoplasmic proteins may exit into the extracellular space. One such protein is S100B, which may exert toxic effects on neighboring cells unless it is removed from the extracellular space, but the mechanisms of this clearance are poorly understood. By using time-lapse confocal microscopy and fluorescently labeled S100B (S100B-Alexa(488) ) and fluorescent dextran (Dextran(546) ), a fluid phase uptake marker, we examined the uptake of fluorescently labeled S100B-Alexa(488) from extracellular space and monitored trafficking of vesicles that internalized S100B-Alexa(488) ...
October 2016: Journal of Neurochemistry
John H Rossmeisl, Kemba Clapp, Theresa E Pancotto, Samantha Emch, John L Robertson, Waldemar Debinski
In humans, high-grade gliomas may infiltrate across the corpus callosum resulting in bihemispheric lesions that may have symmetrical, winged-like appearances. This particular tumor manifestation has been coined a "butterfly" glioma (BG). While canine and human gliomas share many neuroradiological and pathological features, the BG morphology has not been previously reported in dogs. Here, we describe the magnetic resonance imaging (MRI) characteristics of BG in three dogs and review the potential differential diagnoses based on neuroimaging findings...
2016: Frontiers in Veterinary Science
David R Serwanski, Peter Jukkola, Akiko Nishiyama
The node of Ranvier is a functionally important site on the myelinated axon where sodium channels are clustered and regeneration of action potentials occurs, allowing fast saltatory conduction of action potentials. Early ultrastructural studies have revealed the presence of "glia" or "astrocytes" at the nodes. NG2 cells, also known as oligodendrocyte precursor cells or polydendrocytes, which are a resident glial cell population in the mature mammalian central nervous system that is distinct from astrocytes, have also been shown to extend processes that contact the nodes...
July 22, 2016: Journal of Comparative Neurology
C J Garwood, L E Ratcliffe, J E Simpson, P R Heath, P G Ince, S B Wharton
Astrocytes have essential roles in the central nervous system and are also implicated in the pathogenesis of neurodegenerative disease. Forming non-overlapping domains, astrocytes are highly complex cells. Immunohistochemistry to a variety of proteins can be used to study astrocytes in tissue, labelling different cellular components and subpopulations, including GFAP, ALDH1L1, CD44, NDRG2 and amino acid transporters, but none of these label the entire astrocyte population. Increasing heterogeneity is recognised in the astrocyte population, a complexity that is relevant both to their normal function and pathogenic roles...
July 21, 2016: Neuropathology and Applied Neurobiology
Ozgun Gokce, Geoffrey M Stanley, Barbara Treutlein, Norma F Neff, J Gray Camp, Robert C Malenka, Patrick E Rothwell, Marc V Fuccillo, Thomas C Südhof, Stephen R Quake
The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed ten differentiated, distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSNs) that have specific markers and that overexpress genes linked to cognitive disorders and addiction...
July 26, 2016: Cell Reports
Ito Kawakami, Eizo Iseki, Koji Kasanuki, Michiko Minegishi, Kiyoshi Sato, Hiroyuki Hino, Katsuhiko Shibuya, Kohshiro Fujisawa, Shinji Higashi, Haruhiko Akiyama, Akiko Furuta, Masashi Takanashi, Yuanzhe Li, Nobutaka Hattori, Yoshio Mitsuyama, Heii Arai
Clinical phenotypes of hereditary diffuse leukoencephalopathy with spheroids (HDLS), a familial progressive neurodegenerative disorder affecting the white matter of the brain, are heterogenous and may include behavioral and personality changes, memory impairment, parkinsonism, seizure, and spasticity. Thus, HDLS is frequently unrecognized and misdiagnosed. Heterozygous mutations located within the kinase domain of the gene encoding the colony-stimulating factor 1 receptor (CSF1R), a cell surface receptor with key roles in development and innate immunity, have been shown in HDLS...
August 15, 2016: Journal of the Neurological Sciences
Idris A Azeez, Funmilayo Olopade, Claudia Laperchia, Anna Andrioli, Ilaria Scambi, Silas K Onwuka, Marina Bentivoglio, James O Olopade
Environmental exposure to vanadium occurs in areas of persistent burning of fossil fuels; this metal is known to induce oxidative stress and oligodendrocyte damage. Here, we determined whether vanadium exposure (3 mg/kg) in mice during the first 3 postnatal months leads to a sustained neuroinflammatory response. Body weight monitoring, and muscle strength and open field tests showed reduction of body weight gain and locomotor impairment in vanadium-exposed mice. Myelin histochemistry and immunohistochemistry for astrocytes, microglia, and nonphosphorylated neurofilaments revealed striking regional heterogeneity...
September 2016: Journal of Neuropathology and Experimental Neurology
Ahmad Raza Khan, Andrey Chuhutin, Ove Wiborg, Christopher D Kroenke, Jens R Nyengaard, Brian Hansen, Sune Nørhøj Jespersen
Depression is one of the leading causes of disability worldwide. Immense heterogeneity in symptoms of depression causes difficulty in diagnosis, and to date, there are no established biomarkers or imaging methods to examine depression. Unpredictable chronic mild stress (CMS) induced anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains...
July 4, 2016: NeuroImage
Yuki Oe, Otto Baba, Hitoshi Ashida, Kouichi C Nakamura, Hajime Hirase
In the brain, glycogen metabolism has been implied in synaptic plasticity and learning, yet the distribution of this molecule has not been fully described. We investigated cerebral glycogen of the mouse by immunohistochemistry (IHC) using two monoclonal antibodies that have different affinities depending on the glycogen size. The use of focused microwave irradiation yielded well-defined glycogen immunoreactive signals compared with the conventional periodic acid-Schiff method. The IHC signals displayed a punctate distribution localized predominantly in astrocytic processes...
September 2016: Glia
Alejandro Villarreal, Gerardo Rosciszewski, Veronica Murta, Vanesa Cadena, Vanina Usach, Martin M Dodes-Traian, Patricia Setton-Avruj, Luis H Barbeito, Alberto J Ramos
UNLABELLED: Reactive gliosis involving activation and proliferation of astrocytes and microglia, is a widespread but largely complex and graded glial response to brain injury. Astroglial population has a previously underestimated high heterogeneity with cells differing in their morphology, gene expression profile, and response to injury. Here, we identified a subset of reactive astrocytes isolated from brain focal ischemic lesions that show several atypical characteristics. Ischemia-derived astrocytes (IDAs) were isolated from early ischemic penumbra and core...
2016: Frontiers in Cellular Neuroscience
Azadeh Ebrahimi, Marco Skardelly, Irina Bonzheim, Ines Ott, Helmut Mühleisen, Franziska Eckert, Ghazaleh Tabatabai, Jens Schittenhelm
Gliomas are the most frequent intraaxial CNS neoplasms with a heterogeneous molecular background. Recent studies on diffuse gliomas have shown frequent alterations in the genes involved in chromatin remodelling pathways such as α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX). Yet, the reliability of ATRX in predicting isocitrate dehydrogenase (IDH) and H3 histone, family 3A (H3F3A) mutations in gliomas, is unclear.We analysed the ATRX expression status by immunohistochemistry, in a large series of 1064 gliomas and analysed the results in correlation to IDH, H3F3A and loss of heterozygosity (LOH) 1p/19q status in these tumors...
2016: Acta Neuropathologica Communications
Behrouz Moshrefi-Ravasdjani, Pavel Dublin, Gerald Seifert, Katja Jennissen, Christian Steinhäuser, Karl W Kafitz, Christine R Rose
Besides astrocytes and oligodendrocytes, NG2 proteoglycan-expressing cells (NG2 glia) represent a third subtype of macroglia in the brain. Originally described as oligodendrocyte precursor cells, they feature several characteristics not expected from mere progenitor cells, including synaptic connections with neurons. There is accumulating evidence that the properties of NG2 glia differ between different brain regions and developmental stages. To further analyze this proposed heterogeneity, we studied electrophysiological properties, transcript and protein expression, distribution and proliferative capacity of NG2 glia during postnatal development, focusing on the hippocampus and corpus callosum...
June 15, 2016: Brain Structure & Function
Sophie Crespin, Gaëlle Fromont, Michel Wager, Pierre Levillain, Laurent Cronier, Arnaud Monvoisin, Norah Defamie, Marc Mesnil
Precise diagnosis of low and high grades of brain tumors permits determining therapeutical strategies. So far, diagnosis and prognosis of gliomas were based on histological and genetic criteria which need being completed by a panel of molecular markers. Highly distributed in brain, gap junction proteins, connexins, could be considered as markers of glioma progression as previous studies indicated that expression of a connexin type, connexin43 (Cx43), is inversely correlated to tumor grading. However, this assumption was weakened by the low number of glioma samples used...
August 2016: Cancer Medicine
Byung-Wook Kim, Kyoung Hoon Jeong, Jae-Hong Kim, Myungwon Jin, Jong-Heon Kim, Maan-Gee Lee, Dong-Kug Choi, So-Yoon Won, Catriona McLean, Min-Tae Jeon, Ho-Won Lee, Sang Ryong Kim, Kyoungho Suk
UNLABELLED: Lipocalin-2 (LCN2) is a member of the highly heterogeneous secretory protein family of lipocalins and increases in its levels can contribute to neurodegeneration in the adult brain. However, there are no reports on the role of LCN2 in Parkinson's disease (PD). Here, we report for the first time that LCN2 expression is increased in the substantia nigra (SN) of patients with PD. In mouse brains, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment for a neurotoxin model of PD significantly upregulated LCN2 expression, mainly in reactive astrocytes in both the SN and striatum...
May 18, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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