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Granul cell precursors

Aggeliki Giannakopoulou, George A Lyras, Nikolaos Grigoriadis
Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Aging and chronic degenerative disorders have been shown to impair hippocampal neurogenesis, but the consequence of chronic inflammation remains controversial. In this study the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis was used to investigate the long-term effects of T cell-mediated central nervous system inflammation on hippocampal neurogenesis. 5-Bromodeoxyuridine (BrdU)-labeled subpopulations of hippocampal cells in EAE and control mice (coexpressing GFAP, doublecortin, NeuN, calretinin, and S100) were quantified at the recovery phase, 21 days after BrdU administration, to estimate alterations on the rate and differentiation pattern of the neurogenesis process...
October 26, 2016: Journal of Neuroscience Research
Sandra Goebbels, Georg L Wieser, Alexander Pieper, Sonia Spitzer, Bettina Weege, Kuo Yan, Julia M Edgar, Oleksandr Yagensky, Sven P Wichert, Amit Agarwal, Khalad Karram, Nicolas Renier, Marc Tessier-Lavigne, Moritz J Rossner, Ragnhildur Thóra Káradóttir, Klaus-Armin Nave
The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1-mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligodendrocyte progenitor cells, oligodendrocyte differentiation and de novo myelination of parallel fibers. Thus, a neuronal program dependent on the phosphoinositide PI(3,4,5)P3 is sufficient to trigger all steps of myelination...
October 24, 2016: Nature Neuroscience
V Pibiri, A Ravarino, C Gerosa, M C Pintus, V Fanos, G Faa
The aim of this study was to analyze, by immunohistochemistry, the occurrence of stem/progenitor cells localized in the different niches of the developing human cerebellum. To this end, cerebellar samples were obtained from 3 fetuses and 3 newborns ranging, respectively, from 11 to 24 and from 30 to 38 weeks of gestation. Specimens were 10% formalin-fixed, routinely processed and paraffin-embedded; 3 μm-tick sections were immunostained with anti-SOX2 and PAX6 antibodies. Our study evidenced SOX2 and PAX6 immunoreactivity in precursors cells in all six developing human cerebella...
September 19, 2016: European Journal of Histochemistry: EJH
Chen-Jei Hong, Bruce A Hamilton
Zfp423 encodes a 30-zinc finger transcription factor that intersects several canonical signaling pathways. Zfp423 mutations result in ciliopathy-related phenotypes, including agenesis of the cerebellar vermis in mice and Joubert syndrome (JBTS19) and nephronophthisis (NPHP14) in humans. Unlike most ciliopathy genes, Zfp423 encodes a nuclear protein and its developmental expression is complex, leading to alternative proposals for cellular mechanisms. Here we show that Zfp423 is expressed by cerebellar granule cell precursors, that loss of Zfp423 in these precursors leads to cell-intrinsic reduction in proliferation, loss of response to Shh, and primary cilia abnormalities that include diminished frequency of both Smoothened and IFT88 localization...
October 2016: PLoS Genetics
Ravikiran S Yedidi, Amatullah K Fatehi, Cordula Enenkel
The ubiquitin-proteasome system (UPS) plays a critical role in cellular protein homeostasis and is required for the turnover of short-lived and unwanted proteins, which are targeted by poly-ubiquitination for degradation. Proteasome is the key protease of UPS and consists of multiple subunits, which are organized into a catalytic core particle (CP) and a regulatory particle (RP). In Saccharomyces cerevisiae, proteasome holo-enzymes are engaged in degrading poly-ubiquitinated substrates and are mostly localized in the nucleus during cell proliferation...
September 28, 2016: Critical Reviews in Biochemistry and Molecular Biology
Shiwei Wang, Marta Bolós, Rosemary Clark, Carlie L Cullen, Katherine A Southam, Lisa Foa, Tracey C Dickson, Kaylene M Young
The amyloid-β precursor protein (APP) is a transmembrane protein that is widely expressed within the central nervous system (CNS). While the pathogenic dysfunction of this protein has been extensively studied in the context of Alzheimer's disease, its normal function is poorly understood, and reports have often appeared contradictory. In this study we have examined the role of APP in regulating neurogenesis in the adult mouse brain by comparing neural stem cell proliferation, as well as new neuron number and morphology between APP knockout mice and C57bl6 controls...
September 21, 2016: Molecular and Cellular Neurosciences
Frederick Wasinski, Gabriel R Estrela, Aline M Arakaki, Michael Bader, Natalia Alenina, Friederike Klempin, Ronaldo C Araújo
Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later...
2016: Frontiers in Neuroscience
Brigid Ryan, Joanna M Williams
Post-transcriptional control of gene expression by microRNAs provides an important regulatory system within neurons, allowing co-ordinate and fine-tuned expression of plasticity-related proteins. Indeed, specific microRNAs have been shown to be regulated by synaptic activity in the dentate gyrus, and contribute to the regulated gene expression that underlies the persistence of long-term potentiation (LTP), a model of memory. To fully explore the contribution of microRNAs in synaptic plasticity, it is important to characterize the complete microRNA transcriptome in regions such as the dentate gyrus...
September 6, 2016: Neuroscience Letters
Qian Liu, Mei Jiang, Yi Kuang, Xiaoqiong Shu, Jun Li, Matthew W Li, Hedong Li
Granule neuron precursors (GNPs) proliferate under the influence of Sonic hedgehog (Shh) that is secreted by Purkinje neurons during early postnatal cerebellar development. To investigate microRNA (miRNA) function in this developmental process, we conditionally deleted the Dicer1 gene under the activity of human glial fibrillary acidic protein (hGFAP) promoter. We report that Dicer1-ablated GNPs display decreased proliferation and survival at early postnatal stages and that the proliferation defect of mutant GNPs cannot be rescued by treatment of an Shh agonist in vitro as assayed by 5-bromo-2'-deoxyuridine (BrdU) pulse labeling and Shh target gene expression detection...
September 6, 2016: Cerebellum
Paola Caporali, Francesco Bruno, Giampiero Palladino, Jessica Dragotto, Laura Petrosini, Franco Mangia, Robert P Erickson, Sonia Canterini, Maria Teresa Fiorenza
Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by defective intracellular trafficking of exogenous cholesterol. Purkinje cell (PC) degeneration is the main sign of cerebellar dysfunction in both NPC1 patients and animal models. It has been recently shown that a significant decrease in Sonic hedgehog (Shh) expression reduces the proliferative potential of granule neuron precursors in the developing cerebellum of Npc1 (-/-) mice. Pursuing the hypothesis that this developmental defect translates into functional impairments, we have assayed Npc1-deficient pups belonging to the milder mutant mouse strain Npc1 (nmf164) for sensorimotor development from postnatal day (PN) 3 to PN21...
2016: Acta Neuropathologica Communications
Ryoji Funadani, Yoichiro Sogame, Katsuhiko Kojima, Toshikazu Takeshita, Keisuke Yamamoto, Tomoya Tsujizono, Futoshi Suizu, Seiji Miyata, Ken-Ichi Yagyu, Tomohiko Suzuki, Mikihiko Arikawa, Tatsuomi Matsuoka
The cyst wall of the resting cyst of the ciliated protozoan Colpoda cucullus (Nag-1 strain) is composed of several layers of endocyst, a single layer of ectocyst associated with a mucous layer and lepidosomes composed of a fibrous or crystal-like structure. SDS-PAGE showed that the ectocyst associated with lepidosomes and mucous materials contained proteins corresponding to 27 kDa, 31 kDa, 45 kDa and smear bands ranging from 50 to 60 kDa. LC-MS/MS of these proteins revealed that the 45-kDa protein (p45) was elongation factor Tu (EF-Tu)...
August 28, 2016: FEMS Microbiology Letters
Chenlu Zhang, Zhongzhong Ji, Minglei Wang, Weiwei Zhang, Rong Yang, Huanping An, Ru Yang, Daan van Abel, Marie van Dijk, Xiaohang Yang, Guangshuo Ou, Helen He Zhu, Wei-Qiang Gao
Cerebellar granule neuronal progenitors (GNPs) are the precursors of cerebellar granule cells (CGCs) and are believed to be the cell of origin for medulloblastoma (MB), yet the molecular mechanisms governing GNP neurogenesis are poorly elucidated. Here, we demonstrate that storkhead box 1 (Stox1), a forkhead transcriptional factor, has a pivotal role in cerebellar granule neurogenesis and MB suppression. Expression of Stox1 is upregulated along with GNP differentiation and repressed by activation of sonic hedgehog (SHH) signaling...
August 26, 2016: Cell Death and Differentiation
Hans-Peter Lipp, Luca Bonfanti
Mammalian adult neurogenesis has remained enigmatic. Two lines of research have emerged. One focuses on a potential repair mechanism in the human brain. The other aims at elucidating its functional role in the hippocampal formation, chiefly in cognitive processes; however, thus far it has been unsuccessful. Here, we try to recognize the sources of errors and conceptual confusion in comparative studies and neurobehavioral approaches with a focus on mice. Evolutionarily, mammalian adult neurogenesis appears as protracted juvenile neurogenesis originating from precursor cells in the secondary proliferation zones, from where newly formed cells migrate to target regions in the forebrain...
August 24, 2016: Brain, Behavior and Evolution
Ameziane Herzine, Anthony Laugeray, Justyne Feat, Arnaud Menuet, Valérie Quesniaux, Olivier Richard, Jacques Pichon, Céline Montécot-Dubourg, Olivier Perche, Stéphane Mortaud
Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders...
2016: Frontiers in Cellular Neuroscience
Mirella Tanori, Arianna Casciati, Francesco Berardinelli, Simona Leonardi, Emanuela Pasquali, Francesca Antonelli, Barbara Tanno, Paola Giardullo, Alessandro Pannicelli, Gabriele Babini, Ilaria De Stefano, Antonella Sgura, Mariateresa Mancuso, Anna Saran, Simonetta Pazzaglia
Mutations in DNA repair pathways are frequent in human cancers. Hence, gaining insights into the interaction of DNA repair genes is key to development of novel tumor-specific treatment strategies. In this study, we tested the functional relationship in development and oncogenesis between the homologous recombination (HR) factor Rad54 and Parp-1, a nuclear enzyme that plays a multifunctional role in DNA damage signaling and repair. We introduced single or combined Rad54 and Parp-1 inactivating germline mutations in Ptc1 heterozygous mice, a well-characterized model of medulloblastoma, the most common malignant pediatric brain tumor...
July 7, 2016: Oncotarget
Xuting Bian, Hongyu Zhong, Fen Li, Yulong Cai, Xin Li, Lian Wang, Xiaotang Fan
Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum...
September 2, 2016: Biochemical and Biophysical Research Communications
Francine Deprez, Fabia Vogt, Amalia Floriou-Servou, Carlos Lafourcade, Uwe Rudolph, Shiva K Tyagarajan, Jean-Marc Fritschy
Alterations of neuronal activity due to changes in GABAA receptors (GABAA R) mediating tonic inhibition influence different hippocampal functions. Gabra5-null mice and α5 subunit((H105R)) knock-in mice exhibit signs of hippocampal dysfunction, but are capable of improved performance in several learning and memory tasks. Accordingly, alleviating abnormal GABAergic tonic inhibition in the hippocampal formation by selective α5-GABAA R modulators represents a possible therapeutic approach for several intellectual deficit disorders...
September 2016: European Journal of Neuroscience
Steffen K Meurer, Melanie Neß, Sabine Weiskirchen, Philipp Kim, Carmen G Tag, Marlies Kauffmann, Michael Huber, Ralf Weiskirchen
Mast cells (MCs) are a versatile cell type playing key roles in tissue morphogenesis and host defence against bacteria and parasites. Furthermore, they can enhance immunological danger signals and are implicated in inflammatory disorders like fibrosis. This granulated cell type originates from the myeloid lineage and has similarities to basophilic granulocytes, both containing large quantities of histamine and heparin. Immature murine mast cells mature in their destination tissue and adopt either the connective tissue (CTMC) or mucosal (MMC) type...
2016: PloS One
Michele Ammendola, Rosario Sacco, Giuseppe Sammarco, Maria Luposella, Rosa Patruno, Cosmo Damiano Gadaleta, Giovambattista De Sarro, Girolamo Ranieri
Mast cells (MCs) are cells that originate in the bone marrow from pluripotent CD34+ hematopoietic stem cells. Precursors of MCs migrate through the circulation to their target tissues, completing their maturation process into granulated cells under the influence of several microenvironment growth factors. The most important of these factors is the ligand for the c-Kit receptor (c-Kit-R) namely stem cell factor (SCF), secreted mainly by fibroblasts and endothelial cells (ECs). SCF also regulates development, survival and de novo proliferation of MCs...
March 2016: Transfusion Medicine and Hemotherapy
Gregory M Shackleford, Xiang-He Shi, Kimberly S Swanson, Min Y Mahdi, Ignacio Gonzalez-Gomez, Shahab Asgharzadeh, Massimo D'Apuzzo, Anat Erdreich-Epstein, Rex A Moats
Medulloblastomas are the most common malignant pediatric brain tumor and have been divided into four major molecular subgroups. Animal models that mimic the principal molecular aberrations of these subgroups will be important tools for preclinical studies and allow greater understanding of medulloblastoma biology. We report a new transgenic model of medulloblastoma that possesses a unique combination of desirable characteristics including, among others, the ability to incorporate multiple and variable genes of choice and to produce bioluminescent tumors from a limited number of somatic cells within a normal cellular environment...
2016: PloS One
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