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Oligodendrocyte precursor cells

Shi-Fa Zhang, Yan Zhou, Kai-Jing Zhang, Jia-Jie Luan, Shi-Mei Qi
OBJECTIVE: To investigate the effect of Nogo-66 receptor (NgR) silencing with specific small interfering RNA (siRNA) on brain injury repair in preterm rats with brain injury caused by intrauterine infection and related mechanism of action. METHODS: The pregnant Sprague-Dawley rats (with a gestational age of 15 days) were selected, and premature delivery was induced by RU486 or lipopolysaccharide (LPS). The preterm rats delivered by those treated with RU486 were selected as the control group...
October 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Lauren N Russell, Kyle J Lampe
Millions of people suffer from damage or disease to the nervous system that results in a loss of myelin, such as through a spinal cord injury or multiple sclerosis. Diminished myelin levels lead to further cell death in which unmyelinated neurons die. In the central nervous system, a loss of myelin is especially detrimental because of its poor ability to regenerate. Cell therapies such as stem or precursor cell injection have been investigated as stem cells are able to grow and differentiate into the damaged cells; however, stem cell injection alone has been unsuccessful in many areas of neural regeneration...
2016: Cells, Tissues, Organs
Davide Lecca, Davide Marangon, Giusy T Coppolino, Aida Menéndez Méndez, Annamaria Finardi, Gloria Dalla Costa, Vittorio Martinelli, Roberto Furlan, Maria P Abbracchio
In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS)...
October 4, 2016: Scientific Reports
Wenjing Sun, Elizabeth A Matthews, Vicky Nicolas, Susanne Schoch, Dirk Dietrich
Synaptic signaling to NG2-expressing oligodendrocyte precursor cells (NG2 cells) could be key to rendering myelination of axons dependent on neuronal activity, but it has remained unclear whether NG2 glial cells integrate and respond to synaptic input. Here we show that NG2 cells perform linear integration of glutamatergic synaptic inputs and respond with increasing dendritic calcium elevations. Synaptic activity induces rapid Ca(2+) signals mediated by low-voltage activated Ca(2+) channels under strict inhibitory control of voltage-gated A-type K(+) channels...
September 19, 2016: ELife
Mohammad Gol, Davoud Ghorbanian, Samaneh Hassanzadeh, Mohammad Javan, Javad Mirnajafi-Zadeh, Maryam Ghasemi-Kasman
Recent evidence indicates that demyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1mg/kg dosage of FTY720, 1h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i...
September 12, 2016: European Journal of Pharmaceutical Sciences
Ernesto Doncel-Pérez, Manuel Nieto-Sampedro
A combined approach in spinal cord injury (SCI) therapy is the modulation of the cellular and molecular processes involved in glial scarring. Aldaynoglial cells are neural cell precursors with a high capacity to differentiate into neurons, promote axonal growth, wrapping and myelination of resident neurons. These important characteristics of aldaynoglia can be combined with specific inhibition of the RhoGTPase activity in astroglia and microglia that cause reduction of glial proliferation, retraction of glial cell processes and myelin production by oligodendrocytes...
July 2016: Neural Regeneration Research
Karen D Lariosa-Willingham, Elen S Rosler, Jay S Tung, Jason C Dugas, Tassie L Collins, Dmitri Leonoudakis
BACKGROUND: Newly proliferated oligodendrocyte precursor cells (OPCs) migrate and surround lesions of patients with multiple sclerosis (MS) and other demyelinating diseases, but fail to differentiate into oligodendrocytes (OLs) and remyelinate remaining viable axons. The abundance of secreted inflammatory factors within and surrounding these lesions likely plays a major inhibitory role, promoting cell death and preventing OL differentiation and axon remyelination. To identify clinical candidate compounds that may protect existing and differentiating OLs in patients, we have developed a high throughput screening (HTS) assay that utilizes purified rat OPCs...
2016: BMC Research Notes
Junlin Yang, Xuejun Cheng, Jiaxi Shen, Binghua Xie, Xiaofeng Zhao, Zunyi Zhang, Qilin Cao, Ying Shen, Mengsheng Qiu
Although transgenic and knockout mice are widely used to study the specification and differentiation of oligodendrocyte precursor cells (OPCs), mouse primary OPCs are difficult to be purified and maintained, and many in vitro studies have to resort to rat OPCs as substitutes. In this study, we reported that mouse O4 negative early-stage OPCs can be obtained by culturing cortical tissue blocks, and the simultaneous treatment of OPCs with Platelet Derived Growth Factor-AA (PDGFaa), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) is the key for the propagation of mouse OPCs in culture...
2016: Frontiers in Cellular Neuroscience
Karen D Lariosa-Willingham, Elen S Rosler, Jay S Tung, Jason C Dugas, Tassie L Collins, Dmitri Leonoudakis
BACKGROUND: Multiple sclerosis is caused by an autoimmune response resulting in demyelination and neural degeneration. The adult central nervous system has the capacity to remyelinate axons in part through the generation of new oligodendrocytes (OLs). To identify clinical candidate compounds that may promote remyelination, we have developed a high throughput screening (HTS) assay to identify compounds that promote the differentiation of oligodendrocyte precursor cells (OPCs) into OLs...
2016: BMC Research Notes
Toros A Dincman, Jason E Beare, Sujata Saraswat Ohri, Vittorio Gallo, Michal Hetman, Scott R Whittemore
Histone deacetylase (HDAC) inhibition mediated by small molecule HDAC inhibitors (HDACi) has demonstrated divergent effects including toxicity towards transformed cell lines, neuroprotection in neurological disease models, and inhibition of oligodendrocyte precursor cell (OPC) differentiation to mature oligodendrocytes (OL). However, it remains unknown if transient HDAC inhibition may promote OPC survival. Using mouse cortical OPC primary cultures, we investigated the effects of the FDA approved pan-HDACi suberoylanilide hydroxamic acid (SAHA) on OPC survival...
November 2016: International Journal of Developmental Neuroscience
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
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
Guiyun Mi, Yunyun Gao, Shuai Liu, Enmao Ye, Yanyan Li, Xiao Jin, Hongju Yang, Zheng Yang
The cuprizone (CPZ) model has been widely used for the studies of de-and remyelination. The CPZ-exposed mice show oligodendrocyte precursor cells (OPCs) increase and mature oligodendrocytes decrease, suggesting an imbalance between proliferation and differentiation of OPCs. In the first experiment of this study, we examined the expression of cell cycle related genes in brains of mice following CPZ administration for 5 weeks by means of microarray assay. In addition, we performed a double labeling of BrdU and Ki-67 to calculate cell cycle exit index in the mice...
October 17, 2016: Cell Cycle
Malgorzata Ziemka-Nalecz, Joanna Jaworska, Joanna Sypecka, Rafał Polowy, Robert K Filipkowski, Teresa Zalewska
Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a major cause of neonatal death and neurological dysfunctions. Currently, there are no well-established treatments to reduce brain damage and its long-term sequel in infants. Recently, reported data show that histone deacetylase inhibitors provide neuroprotection in adult stroke models. However, the proof of their relevance in vivo after neonatal HI brain injury remains particularly limited. In the present study, we show neuroprotective/neurogenic effect of sodium butyrate (SB), one of histone deacetylase inhibitors (HDACis), in the dentate gyrus of HI-injured immature rats...
August 30, 2016: Molecular Neurobiology
Masae Naruse, Yasuki Ishizaki, Kazuhiro Ikenaka, Aoi Tanaka, Seiji Hitoshi
Oligodendrocyte precursor cells (OPCs) appear in the late embryonic brain, mature into oligodendrocytes (OLs), and form myelin in the postnatal brain. It has been proposed that early born OPCs derived from the ventral forebrain are eliminated postnatally and late-born OLs predominate in the adult mouse cortex. However, the temporal and regional niche for cortical OL generation, which persists throughout life in adult mammals, remains to be determined. Our recent study provides new insight into self-renewing and multipotent neural stem cells (NSCs)...
August 29, 2016: Journal of Physiological Sciences: JPS
Hae Ung Lee, Sudip Nag, Agata Blasiak, Yan Jin, Nitish V Thakor, In Hong Yang
Myelination is governed by neuron-glia communication, which in turn is modulated by neural activity. The exact mechanisms remain elusive. We developed a novel in vitro optogenetic stimulation platform that facilitates subcellular activity induction in hundreds of neurons simultaneously. The light isolation was achieved by creating a bio-compatible, light-absorbent, black microfluidic device integrated with a programmable, high-power LED array. The system was applied to a compartmentalized culture of primary neurons whose distal axons were interacting with oligodendrocyte precursor cells...
August 29, 2016: ACS Chemical Neuroscience
Ruilin Yang, Jiyong He, Yuliang Wang
After spinal cord injury (SCI), there is an acute phase of alternatively activated (M2) macrophage infiltration, followed by a long-lasting phase of classically activated (M1) macrophage accumulation in the wound, which is believed to derail healing and compromize organ functions. Thus, agents which are able to modulate macrophage phenotypes may provide significant benefits to SCI patients. In the present study, we demonstrate that the niacin receptor HCA2 is specifically expressed on the cell surface of M1 but not M2 macrophages...
August 26, 2016: European Journal of Pharmacology
Marta Boccazzi, Davide Lecca, Davide Marangon, Fabio Guagnini, Maria P Abbracchio, Stefania Ceruti
Oligodendrocyte precursor cells (OPCs, also called NG2 cells) are scattered throughout brain parenchyma, where they function as a reservoir to replace lost or damaged oligodendrocytes, the myelin-forming cells. The hypothesis that, under some circumstances, OPCs can actually behave as multipotent cells, thus generating astrocytes and neurons as well, has arisen from some in vitro and in vivo evidence, but the molecular pathways controlling this alternative fate of OPCs are not fully understood. Their identification would open new opportunities for neuronal replace strategies, by fostering the intrinsic ability of the brain to regenerate...
August 20, 2016: Purinergic Signalling
Filip Petković, Iain L Campbell, Berta Gonzalez, Bernardo Castellano
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Interleukin (IL)-6 is a pleiotropic cytokine with a potential role in MS. Here we used transgenic mice with astrocyte-targeted production of IL-6 (GFAP-IL6Tg) to study the effect of IL-6 in the cuprizone-induced demyelination paradigm, which is an experimental model of de- and re-myelination, both hallmarks of MS. Our results demonstrated that cuprizone-treated GFAP-IL6Tg mice showed a significant reduction in astroglial and especially microglial activation/accumulation in the corpus callosum in comparison with the corresponding cuprizone-treated wild type (WT)...
August 18, 2016: Glia
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