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Johanna Flygt, Fredrik Clausen, Niklas Marklund
BACKGROUND: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI...
October 17, 2016: Restorative Neurology and Neuroscience
Zhimin Ou, Yuxia Sun, Li Lin, Nachun You, Xue Liu, Hongchao Li, Yanchen Ma, Lei Cao, Ying Han, Min Liu, Yaqi Deng, Luming Yao, Q Richard Lu, Ying Chen
: Demyelinating diseases, such as multiple sclerosis, are known to result from acute or chronic injury to the myelin sheath and inadequate remyelination; however, the underlying molecular mechanisms remain unclear. Here, we performed genome occupancy analysis by chromatin immunoprecipitation sequencing in oligodendrocytes in response to lysolecithin-induced injury and found that Olig2 and its downstream target Gpr17 are critical factors in regulating oligodendrocyte survival. After injury to oligodendrocytes, Olig2 was significantly upregulated and transcriptionally targeted the Gpr17 locus...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ryan L O'Hare Doig, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Sarah A Dunlop, Livia Hool, Melinda Fitzgerald
Combinations of Ca(2+) channel inhibitors have been proposed as an effective means to prevent excess Ca(2+) flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca(2+) concentrations. Here, the effects of combinations of Lomerizine (Lom), YM872, memantine and/or oxATP to block voltage gated Ca(2+) channels, Ca(2+) permeable AMPA receptors, NMDA receptors and purinergic P2X7 receptors (P2X7R) respectively, on Ca(2+) concentration and viability of primary mixed cortical cultures exposed to hydrogen peroxide (H2O2) insult, were assessed...
October 7, 2016: Neuroscience
Daniel Cortés, Yolanda Robledo-Arratia, Ricardo Hernández-Martínez, Itzel Escobedo-Ávila, José Bargas, Iván Velasco
Embryonic stem cells (ESC) are pluripotent and thus can differentiate into every cell type present in the body. Directed differentiation into motor neurons (MNs) has been described for pluripotent cells. Although neurotrophic factors promote neuronal survival, their role in neuronal commitment is elusive. Here, we developed double-transgenic lines of mouse ESC (mESC) that constitutively produce glial cell line-derived neurotrophic factor (GDNF) and also contain a GFP reporter, driven by HB9, which is expressed only by postmitotic MNs...
2016: Frontiers in Cellular Neuroscience
Hui Wang, Michael P Matise
The generation of functionally distinct neuronal subtypes within the vertebrate central nervous system (CNS) requires the precise regulation of progenitor gene expression in specific neuronal territories during early embryogenesis. Accumulating evidence has implicated histone deacetylase (HDAC) proteins in cell specification, proliferation, and differentiation in diverse embryonic and adult tissues. However, although HDAC proteins have shown to be expressed in the developing vertebrate neural tube, their specific role in CNS neural progenitor fate specification remains unclear...
2016: PloS One
Amanda L Edwards, Dimphna H Meijer, Rachel M Guerra, Remco J Molenaar, John A Alberta, Federico Bernal, Gregory H Bird, Charles D Stiles, Loren D Walensky
Basic helix-loop-helix (bHLH) transcription factors play critical roles in organism development and disease by regulating cell proliferation and differentiation. Transcriptional activity, whether by bHLH homo- or heterodimerization, is dependent on protein-protein and protein-DNA interactions mediated by α-helices. Thus, α-helical decoys have been proposed as potential targeted therapies for pathologic bHLH transcription. Here, we developed a library of stabilized α-helices of OLIG2 (SAH-OLIG2) to test the capacity of hydrocarbon-stapled peptides to disrupt OLIG2 homodimerization, which drives the development and chemoresistance of glioblastoma multiforme, one of the deadliest forms of human brain cancer...
October 4, 2016: ACS Chemical Biology
Séverine Martin-Lannerée, Sophie Halliez, Théo Z Hirsch, Julia Hernandez-Rapp, Bruno Passet, Céline Tomkiewicz, Ana Villa-Diaz, Juan-Maria Torres, Jean-Marie Launay, Vincent Béringue, Jean-Luc Vilotte, Sophie Mouillet-Richard
The prion protein is infamous for its involvement in a group of neurodegenerative diseases known as Transmissible Spongiform Encephalopathies. In the longstanding quest to decipher the physiological function of its cellular isoform, PrP(C) , the discovery of its participation to the self-renewal of hematopoietic and neural stem cells has cast a new spotlight on its potential role in stem cell biology. However, still little is known on the cellular and molecular mechanisms at play. Here, by combining in vitro and in vivo murine models of PrP(C) depletion, we establish that PrP(C) deficiency severely affects the Notch pathway, which plays a major role in neural stem cell maintenance...
September 19, 2016: Stem Cells
Robert Kupp, Lior Shtayer, An-Chi Tien, Emily Szeto, Nader Sanai, David H Rowitch, Shwetal Mehta
The basic helix-loop-helix (bHLH) transcription factor OLIG2 is a master regulator of oligodendroglial fate decisions and tumorigenic competence of glioma stem-like cells (GSCs). However, the molecular mechanisms underlying dysregulation of OLIG2 function during gliomagenesis remains poorly understood. Here, we show that OLIG2 modulates growth factor signaling in two distinct populations of GSCs, characterized by expression of either the epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor alpha (PDGFRα)...
September 13, 2016: Cell Reports
Augusto F Schmidt, Paranthaman S Kannan, Claire A Chougnet, Steve C Danzer, Lisa A Miller, Alan H Jobe, Suhas G Kallapur
BACKGROUND: Chorioamnionitis is associated with an increased risk of brain injury in preterm neonates. Inflammatory changes in brain could underlie this injury. Here, we evaluated whether neuroinflammation is induced by chorioamnionitis in a clinically relevant model. METHODS: Rhesus macaque fetuses were exposed to either intra-amniotic (IA) saline, or IA lipopolysaccharide (LPS) (1 mg) 16 or 48 h prior to delivery at 130 days (85 % of gestation) (n = 4-5 animals/group)...
2016: Journal of Neuroinflammation
Martin H M Sailer, Durga Sarvepalli, Catherine Brégère, Urs Fisch, Marin Guentchev, Michael Weller, Raphael Guzman, Bernhard Bettler, Arkasubhra Ghosh, Gregor Hutter
Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood...
2016: Journal of Visualized Experiments: JoVE
Ana Cathia Magalhães, Claudio Rivera
The proliferative pool of neural progenitor cells is maintained by exquisitely controlled mechanisms for cell cycle regulation. The Na-K-Cl cotransporter (NKCC1) is important for regulating cell volume and the proliferation of different cell types in vitro. NKCC1 is expressed in ventral telencephalon of embryonic brains suggesting a potential role in neural development of this region. The ventral telencephalon is a major source for both interneuron and oligodendrocyte precursor cells. Whether NKCC1 is involved in the proliferation of these cell populations remains unknown...
2016: Frontiers in Cellular Neuroscience
Lukasz Mateusz Szewczyk, Nikola Brozko, Andrzej Nagalski, Iris Röckle, Sebastian Werneburg, Herbert Hildebrandt, Marta Barbara Wisniewska, Jacek Kuznicki
ST8SIA2 is a polysialyltransferase that attaches polysialic acid to the glycoproteins NCAM1 and CADM1. Polysialylation is involved in brain development and plasticity. ST8SIA2 is a schizophrenia candidate gene, and St8sia2(-/-) mice exhibit schizophrenia-like behavior. We sought to identify new pathological consequences of ST8SIA2 deficiency. Our proteomic analysis suggested myelin impairment in St8sia2(-/-) mice. Histological and immune staining together with Western blot revealed that the onset of myelination was not delayed in St8sia2(-/-) mice, but the content of myelin was lower...
August 18, 2016: Glia
Ewa Ferensztajn-Rochowiak, Maciej Tarnowski, Jerzy Samochowiec, Michal Michalak, Mariusz Z Ratajczak, Janusz K Rybakowski
Neuroinflammation, with microglial activation as an important element, plays a role in the pathogenesis of bipolar disorder (BD). Also, in mood disorders, pathological changes have been demonstrated in macroglial cells, such as astrocyctes and oligodendrocytes. Postmortem brain studies of BD patients to assess glial cells, such as astrocytes and oligodendrocytes and their markers such as glial fibrillary acidic protein (GFAP), Olig1 and Olig2, produced controversial results. On the other hand, investigation of these markers in the peripheral blood of such patients has not been performed so far...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Jun Ju, Qian Liu, Yang Zhang, Yuanxiu Liu, Mei Jiang, Liguo Zhang, Xuelian He, Chenchen Peng, Tao Zheng, Q Richard Lu, Hedong Li
The oligodendrocyte transcription factor Olig2 plays a crucial role in the neurogenesis of both spinal cord and brain. In the cerebellum, deletion of both Olig2 and Olig1 results in impaired genesis of Purkinje cells (PCs) and Pax2(+) interneurons. Here, we perform an independent study to show that Olig2 protein is transiently expressed in the cerebellar ventricular zone (VZ) during a period when PCs are specified. Further analyses demonstrate that Olig2 is expressed in both cerebellar VZ progenitors and early-born neurons...
2016: Scientific Reports
Igor F Tsigelny, Valentina L Kouznetsova, Nathan Lian, Santosh Kesari
Oligodendrocyte lineage transcription factor 2 (OLIG2) plays a pivotal role in glioma development. Here we conducted a comprehensive study of the critical gene regulatory networks involving OLIG2. These include the networks responsible for OLIG2 expression, its translocation to nucleus, cell cycle, epigenetic regulation, and Rho-pathway interactions. We described positive feedback loops including OLIG2: loops of epigenetic regulation and loops involving receptor tyrosine kinases. These loops may be responsible for the prolonged oncogenic activity of OLIG2...
July 16, 2016: Oncotarget
Kouko Tatsumi, Hiroaki Okuda, Shoko Morita-Takemura, Tatsuhide Tanaka, Ayami Isonishi, Takeaki Shinjo, Yuki Terada, Akio Wanaka
Changes in astrocyte morphology are primarily attributed to the fine processes where intimate connections with neurons form the tripartite synapse and participate in neurotransmission. Recent evidence has shown that neurotransmission induces dynamic synaptic remodeling, suggesting that astrocytic fine processes may adapt their morphologies to the activity in their environment. To illustrate such a neuron-glia relationship in morphological detail, we employed a double transgenic Olig2(CreER/WT); ROSA26-GAP43-EGFP mice, in which Olig2-lineage cells can be visualized and traced with membrane-targeted GFP...
2016: Frontiers in Cellular Neuroscience
Ji Hyeon Ahn, Bai Hui Chen, Bich Na Shin, Jeong Hwi Cho, In Hye Kim, Joon Ha Park, Jae Chul Lee, Hyun Jin Tae, Yun Lyul Lee, Jaesuk Lee, Kyunghee Byun, Goo-Bo Jeong, Bonghee Lee, Young-Myeong Kim, Moo-Ho Won, Soo Young Choi
Oligodendrocytes play a crucial role in creating the myelin sheath that is an important component in the neural transmission. In an animal model of transient cerebral ischemia, application of oligodendrocyte progenitor cells (OPCs) have not been yet reported. In this study, the effects of F3.Olig2 transplantation on memory and cognitive dysfunction, in the aged gerbil induced by ischemic stroke were investigated. To investigate the possible mechanisms, changes in the expression of myelin basic protein (MBP), oligodendrocytes specific protein (OSP) and brain-derived neurotrophic factor (BDNF) were examined...
July 20, 2016: Cell Transplantation
Yean Ju Hong, Jong Soo Kim, Hyun Woo Choi, Hyuk Song, Chankyu Park, Jeong Tae Do
Pluripotent stem cells have the potential to differentiate into all cell types of the body in vitro through embryoid body formation or in vivo through teratoma formation. In this study, we attempted to generate in vivo neural stem cells (NSCs) differentiated through teratoma formation using Olig2-GFP transgenic embryonic stem cells (ESCs). After 4 to 6 weeks of injection with Olig2-GFP transgenic ESCs, Olig2-GFP(+) NSCs were identified in teratomas formed in immunodeficient mice. Interestingly, 4-week-old teratomas contained higher percentage of Olig2-GFP(+) cells (∼11%) than 6-week-old teratomas (∼3%)...
September 1, 2016: Stem Cells and Development
Dae-Kwon Bae, Dongsun Park, Sun Hee Lee, Goeun Yang, Jangbeen Kyung, Dajeong Kim, Kyungha Shin, Ehn-Kyoung Choi, Gonhyung Kim, Jin Tae Hong, Seung U Kim, Yun-Bae Kim
Since multiple sclerosis (MS) is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs) with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG-) induced experimental autoimmune encephalomyelitis (EAE) model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 10(6)/mouse) were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3...
2016: Stem Cells International
G Christopher Tan, Esteban O Mazzoni, Hynek Wichterle
The motor neuron progenitor domain in the ventral spinal cord gives rise to multiple subtypes of motor neurons and glial cells. Here, we examine whether progenitors found in this domain are multipotent and which signals contribute to their cell-type-specific differentiation. Using an in vitro neural differentiation model, we demonstrate that motor neuron progenitor differentiation is iteratively controlled by Notch signaling. First, Notch controls the timing of motor neuron genesis by repressing Neurogenin 2 (Ngn2) and maintaining Olig2-positive progenitors in a proliferative state...
July 26, 2016: Cell Reports
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