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Philipp Abe, Hannah M Wüst, Sebastian J Arnold, Serge A van de Pavert, Ralf Stumm
Adult hippocampal neurogenesis is implicated in learning and memory processing. It is tightly controlled at several levels including progenitor proliferation as well as migration, differentiation and integration of new neurons. Hippocampal progenitors and immature neurons reside in the subgranular zone (SGZ) and are equipped with the CXCL12-receptor CXCR4 which contributes to defining the SGZ as neurogenic niche. The atypical CXCL12-receptor CXCR7 functions primarily by sequestering extracellular CXCL12 but whether CXCR7 is involved in adult neurogenesis has not been assessed...
March 14, 2018: Glia
Lorena Colás, Maria Domercq, Pedro Ramos-Cabrer, Ana Palma, Vanessa Gómez-Vallejo, Daniel Padro, Sandra Plaza-García, Krishna R Pulagam, Makoto Higuchi, Carlos Matute, Jordi Llop, Abraham Martín
In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and ex vivo evaluation of α7 nAChRs expression after transient middle cerebral artery occlusion (MCAO) was carried out using PET imaging with [11 C]NS14492 and immunohistochemistry (IHC)...
March 12, 2018: Glia
Gunnar Poplawski, Tetsuhiro Ishikawa, Coralie Brifault, Corinne Lee-Kubli, Robert Regestam, Kenneth W Henry, Yasuhiro Shiga, HyoJun Kwon, Seiji Ohtori, Steven L Gonias, Wendy M Campana
Sensory neurons in the PNS demonstrate substantial capacity for regeneration following injury. Recent studies have identified changes in the transcriptome of sensory neurons, which are instrumental for axon regeneration. The role of Schwann cells (SCs) in mediating these changes remains undefined. We tested the hypothesis that SCs regulate expression of genes in sensory neurons before and after PNS injury by comparing mice in which LDL Receptor-related Protein-1 (LRP1) is deleted in SCs (scLRP1-/- mice) with wild-type (scLRP1+/+ ) littermates...
March 9, 2018: Glia
Dale George, Paige Ahrens, Stephen Lambert
Satellite glial cells (SGCs) are glial cells in the peripheral nervous system that form sheaths around the neuronal cell body. This unique arrangement of SGCs allows it to exert a highly regulated control over the neuronal microenvironment. Not much is known about the origin of SGCs. In this study, we examine the development of SGCs. We show that rat SGCs develop postnatally and these cells express a number of markers associated with Schwann cell precursors, in particular cadherin-19 (CDH19) even in adult DRGs...
March 9, 2018: Glia
Reut Hilu-Dadia, Ketty Hakim-Mishnaevski, Flonia Levy-Adam, Estee Kurant
Development of the central nervous system involves elimination of superfluous neurons through apoptosis and subsequent phagocytosis. In Drosophila, this occurs mainly during three developmental stages: embryogenesis, metamorphosis and emerging adult. Two transmembrane glial phagocytic receptors, SIMU (homolog of the mammalian Stabilin-2) and Draper (homolog of the mammalian MEGF10 and Jedi), mediate glial phagocytosis of apoptotic neurons during embryogenesis. However, less is known about the removal of apoptotic neurons during later stages of development...
March 9, 2018: Glia
Hang-Jing Wu, Xue-Yan Li, Wen-Jing Qian, Qian Li, Shu-Yue Wang, Min Ji, Yuan-Yuan Ma, Feng Gao, Xing-Huai Sun, Xin Wang, Yanying Miao, Xiong-Li Yang, Zhongfeng Wang
Müller cell gliosis is a common response in many retinal pathological conditions. We previously demonstrated that downregulation of Kir channels contributes to Müller cell gliosis in a rat chronic ocular hypertension (COH) model. Here, the possible involvement of outward K+ currents in Müller cell gliosis was investigated. Outward K+ current densities in Müller cells isolated from COH rats, as compared with those in normal rats, showed a significant increase, which was mainly contributed by large-conductance Ca2+ -activated K+ (BKCa ) channels...
March 6, 2018: Glia
Monika Plescher, Gerald Seifert, Jan Niklas Hansen, Peter Bedner, Christian Steinhäuser, Annett Halle
Microglia, the central nervous system resident innate immune cells, cluster around Aβ plaques in Alzheimer's disease (AD). The activation phenotype of these plaque-associated microglial cells, and their differences to microglia distant to Aβ plaques, are incompletely understood. We used novel three-dimensional cell analysis software to comprehensively analyze the morphological properties of microglia in the TgCRND8 mouse model of AD in spatial relation to Aβ plaques. We found strong morphological changes exclusively in plaque-associated microglia, whereas plaque-distant microglia showed only minor changes...
March 1, 2018: Glia
Dominika Drulis-Fajdasz, Agnieszka Gizak, Tomasz Wójtowicz, Jacek R Wiśniewski, Dariusz Rakus
Lactate derived from astrocytic glycogen has been shown to support memory formation in hippocampi of young animals, inhibiting it in old animals. Here we show, using quantitative mass spectrometry-based proteomics, immunofluorescence, and qPCR that aging is associated with an increase of glycogen metabolism enzymes concentration and shift in their localization from astrocytes to neurons. These changes are accompanied with reorganization of hippocampal energy metabolism which is manifested by elevated capacity of aging neurons to oxidize glucose in glycolysis and mitochondria, and decreased ability for fatty acids utilization...
March 1, 2018: Glia
Miriam Mecha, Ana Feliú, Isabel Machín, Cesar Cordero, Francisco Carrillo-Salinas, Leyre Mestre, Gloria Hernández-Torres, Silvia Ortega-Gutiérrez, María L López-Rodríguez, Fernando de Castro, Diego Clemente, Carmen Guaza
The innate immune response is mediated by primary immune modulators such as cytokines and chemokines that together with immune cells and resident glia orchestrate CNS immunity and inflammation. Growing evidence supports that the endocannabinoid 2-arachidonoylglycerol (2-AG) exerts protective actions in CNS injury models. Here, we used the acute phase of Theiler's virus induced demyelination disease (TMEV-IDD) as a model of acute neuroinflammation to investigate whether 2-AG modifies the brain innate immune responses to TMEV and CNS leukocyte trafficking...
February 27, 2018: Glia
Ana Gutiérrez-Rodríguez, Itziar Bonilla-Del Río, Nagore Puente, Sonia M Gómez-Urquijo, Christine J Fontaine, Jon Egaña-Huguet, Izaskun Elezgarai, Sabine Ruehle, Beat Lutz, Laurie M Robin, Edgar Soria-Gómez, Luigi Bellocchio, Jalindar D Padwal, Mario van der Stelt, Juan Mendizabal-Zubiaga, Leire Reguero, Almudena Ramos, Inmaculada Gerrikagoitia, Giovanni Marsicano, Pedro Grandes
Astroglial type-1 cannabinoid (CB1 ) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so-called tripartite synapse formed by pre- and post-synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB1 receptors. In particular, brain CB1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB1 receptors are present in astroglial mitochondria has remained unknown...
February 26, 2018: Glia
Mika Takarada-Iemata, Akifumi Yoshikawa, Hieu Minh Ta, Nahoko Okitani, Takumi Nishiuchi, Yasuhiro Aida, Tomoya Kamide, Tsuyoshi Hattori, Hiroshi Ishii, Takashi Tamatani, Thuong Manh Le, Jureepon Roboon, Yasuko Kitao, Tomohiro Matsuyama, Mitsutoshi Nakada, Osamu Hori
Disruption of the blood-brain barrier (BBB) following cerebral ischemia is closely related to the infiltration of peripheral cells into the brain, progression of lesion formation, and clinical exacerbation. However, the mechanism that regulates BBB integrity, especially after permanent ischemia, remains unclear. Here, we present evidence that astrocytic N-myc downstream-regulated gene 2 (NDRG2), a differentiation- and stress-associated molecule, may function as a modulator of BBB permeability following ischemic stroke, using a mouse model of permanent cerebral ischemia...
February 24, 2018: Glia
L Felipe Barros, Angus Brown, Raymond A Swanson
Early views of glia as relatively inert, housekeeping cells have evolved, and glia are now recognized as dynamic cells that not only respond to neuronal activity but also sense metabolic changes and regulate neuronal metabolism. This evolution has been aided in part by technical advances permitting progressively better spatial and temporal resolution. Recent advances in cell-type specific genetic manipulation and sub-cellular metabolic probes promise to further this evolution by enabling study of metabolic interactions between intertwined fine neuronal and glial processes in vivo...
February 24, 2018: Glia
Caterina Rizzi, Alexia Tiberi, Michela Giustizieri, Maria Cristina Marrone, Francesco Gobbo, Nicola Maria Carucci, Giovanni Meli, Ivan Arisi, Mara D'Onofrio, Silvia Marinelli, Simona Capsoni, Antonino Cattaneo
Microglia are the sentinels of the brain but a clear understanding of the factors that modulate their activation in physiological and pathological conditions is still lacking. Here we demonstrate that Nerve Growth Factor (NGF) acts on microglia by steering them toward a neuroprotective and anti-inflammatory phenotype. We show that microglial cells express functional NGF receptors in vitro and ex vivo. Our transcriptomic analysis reveals how, in primary microglia, NGF treatment leads to a modulation of motility, phagocytosis and degradation pathways...
February 23, 2018: Glia
Valéria Pereira Ferrer, Vivaldo Moura Neto, Rolf Mentlein
An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process...
February 21, 2018: Glia
Corinne Barat, Alizé Proust, Alexandre Deshiere, Mathieu Leboeuf, Jean Drouin, Michel J Tremblay
The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4+ T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary...
February 21, 2018: Glia
Brian Chiou, Elisabeth Lucassen, Michael Sather, Asha Kallianpur, James Connor
Deficiency of trophic factors relating to the survival of oligodendrocytes, combined with direct interactions with the immune system, are favored paradigms that are increasingly implicated in demyelinating diseases of the central nervous system. We and others have previously shown that Sema4A and H-ferritin interact through the T-cell immunoglobulin and mucin domain (Tim-2) receptor in mice. H-ferritin has been identified as the iron delivery protein for oligodendrocytes, whereas Sema4A causes a direct cytotoxic effect...
February 19, 2018: Glia
Jia-Lin Mo, Qi Liu, Zeng-Wei Kou, Kun-Wei Wu, Ping Yang, Xian-Hua Chen, Feng-Yan Sun
Reactive astrocytes induced by ischemia can transdifferentiate into mature neurons. This neurogenic potential of astrocytes may have therapeutic value for brain injury. Epigenetic modifications are widely known to involve in developmental and adult neurogenesis. PAX6, a neurogenic fate determinant, contributes to the astrocyte-to-neuron conversion. However, it is unclear whether microRNAs (miRs) modulate PAX6-mediated astrocyte-to-neuron conversion. In the present study we used bioinformatic approaches to predict miRs potentially targeting Pax6, and transient middle cerebral artery occlusion (MCAO) to model cerebral ischemic injury in adult rats...
February 16, 2018: Glia
Sarrabeth Stone, Shuangchan Wu, Stephanie Jamison, Wilaiwan Durose, Jean Pierre Pallais, Wensheng Lin
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) play a critical role in immune-mediated demyelinating diseases, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), by regulating the viability of oligodendrocytes. Our previous studies show that activation of the PERK branch of the UPR protects myelinating oligodendrocytes against ER stress in young, developing mice that express IFN-γ, a key pro-inflammatory cytokine in MS and EAE, in the CNS...
February 13, 2018: Glia
Giusy T Coppolino, Davide Marangon, Camilla Negri, Gianluca Menichetti, Marta Fumagalli, Paolo Gelosa, Leda Dimou, Roberto Furlan, Davide Lecca, Maria P Abbracchio
Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreERT2 xCAG-eGFP mice) allowing to follow the final fate of GPR17+ cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult...
February 9, 2018: Glia
Raya Eilam, Menahem Segal, Rafael Malach, Michael Sela, Ruth Arnon, Rina Aharoni
To elucidate mechanisms contributing to cortical pathology in multiple sclerosis (MS), we investigated neurovascular aberrations, in particular the association of astrocytes with cortical neurons and blood vessels, in mice induced with experimental autoimmune encephalomyelitis (EAE). Blood-brain barrier (BBB) dysfunction was evident by leakage of the tracer sodium fluorescein, along with reduced expression of claudin-5 by endothelial cells and desmin by pericytes. Immunohistological and ultrastructural analyses revealed detachment of the astroglial cell bodies from the blood vessels and loss of their connections with both the blood vessels and the neuronal synapses...
February 9, 2018: Glia
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