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Sample records for glial precursors clear

  1. Gradient isolation of glial cells: evidence that flat epithelial cells are astroglial cell precursors.

    PubMed

    Meller, K

    1987-07-01

    Discontinuous gradients of metrizamide were used to separate the cell components of monolayers of primary cultures of embryonic rat brains. These primary cell cultures were of two types: long-term cultures (more than a year) of embryonic rat brain, which contained several glial cell types, and monolayers of cell cultures (several weeks old), which contained a complex population of cells, including neuronal elements. The gradient separation produces fractions of pure flat epithelial cells that are able to survive and proliferate. After a few days, all flat epithelial cells become confluent and show a positive reaction to glial fibrillary acidic protein (GFAP); this indicates that these cells astroglial precursor cells. Following their maintenance in vitro for several months, all cultures give rise to a pure population of astrocytes identified not only by their characteristic morphology, but also by their content of GFAP. It is proposed that the differentiation controls are dependent on cell interactions that are influenced by the composition of the cell population and/or the molecular growth and differentiation factors released by these cells into the medium.

  2. Reversal of developmental restrictions in neural crest lineages: Transition from Schwann cells to glial-melanocytic precursors in vitro

    PubMed Central

    Dupin, Elisabeth; Real, Carla; Glavieux-Pardanaud, Corinne; Vaigot, Pierre; Le Douarin, Nicole M.

    2003-01-01

    In vertebrate embryos, diversification of the lineages arising from the neural crest (NC) is controlled to a large extent by environmental factors. In previous work, we showed that endothelin 3 (ET3) peptide favors the development of glial and melanocytic NC precursors in vitro. This factor is also capable of inducing proliferation of cultured epidermal pigment cells and their conversion to glia. ET3 therefore strongly promotes the emergence of melanocytic and glial phenotypes from precursors and acts on the maintenance of these phenotypes. In the present work, we explored the capacity of ET3 to reprogram glial cells into melanocytes. Schwann cells expressing glial-specific markers [such as the Schwann cell myelin protein (SMP)] were isolated from sciatic nerves of quail embryos and cultured in vitro. We found that ET3 promotes cell growth and sequential expression of melanocyte differentiation markers in cultures of purified SMP-expressing cells, whereas it had no significant effect on SMP-negative cells from the same nerves. Moreover, we provide evidence for the transition of differentiated Schwann cells to melanocytes in clonal cultures. This transition involves the production of a mixed progeny of melanoblasts/melanocytes, glia, and cells bearing differentiation markers of both phenotypes. Therefore, Schwann cells exposed to ET3 transdifferentiate to melanocytes through reversion to the stage of bipotent glial-melanocytic NC precursors. These findings show that NC-derived pigment and glial cells are phenotypically unstable in vitro and may undergo reversal of precursor hierarchy to function as bipotent stem cells. PMID:12702775

  3. Examining the properties and therapeutic potential of glial restricted precursors in spinal cord injury

    PubMed Central

    Hayakawa, Kazuo; Haas, Christopher; Fischer, Itzhak

    2016-01-01

    In the aftermath of spinal cord injury, glial restricted precursors (GRPs) and immature astrocytes offer the potential to modulate the inflammatory environment of the injured spinal cord and promote host axon regeneration. Nevertheless clinical application of cellular therapy for the repair of spinal cord injury requires strict quality-assured protocols for large-scale production and preservation that necessitates long-term in vitro expansion. Importantly, such processes have the potential to alter the phenotypic and functional properties and thus therapeutic potential of these cells. Furthermore, clinical use of cellular therapies may be limited by the inflammatory microenvironment of the injured spinal cord, altering the phenotypic and functional properties of grafted cells. This report simulates the process of large-scale GRP production and demonstrates the permissive properties of GRP following long-term in vitro culture. Furthermore, we defined the phenotypic and functional properties of GRP in the presence of inflammatory factors, and call attention to the importance of the microenvironment of grafted cells, underscoring the importance of modulating the environment of the injured spinal cord. PMID:27212899

  4. Glial commitment of mesencephalic neural precursor cells expanded as neurospheres precludes their engagement in niche-dependent dopaminergic neurogenesis.

    PubMed

    Baizabal, José-Manuel; Cano-Martínez, Agustina; Valencia, Concepción; Santa-Olalla, Jesús; Young, Kaylene M; Rietze, Rodney L; Bartlett, Perry F; Covarrubias, Luis

    2012-05-01

    Neural precursor cells (NPCs) with high proliferative potential are commonly expanded in vitro as neurospheres. As a population, neurosphere cells show long-term self-renewal capacity and multipotentiality in vitro. These features have led to the assumption that neurosphere cells represent an expansion of the endogenous NPCs residing within the embryonic and adult brain. If this is the case, in principle, bona-fide expansion of endogenous NPCs should not significantly affect their capacity to respond to their original niche of differentiation. To address this issue, we generated primary neurospheres from the dopaminergic niche of the ventral mesencephalon and then transplanted these cells to their original niche within mesencephalic explant cultures. Primary neurosphere cells showed poor capacity to generate dopaminergic neurons in the mesencephalic niche of dopaminergic neurogenesis. Instead, most primary neurosphere cells showed glial commitment as they differentiated into astrocytes in an exclusively neurogenic niche. Subculture of primary cells demonstrated that the neurosphere assay does not amplify niche-responsive dopaminergic progenitors. Further, neurospheres cells were largely unable to acquire the endogenous positional identity within the Nkx6.1(+), Nkx2.2(+), and Pax7(+) domains of mesencephalic explants. Finally, we demonstrate that our observations are not specific for embryonic mesencephalic cells, as NPCs in the adult subventricular zone also showed an intrinsic fate switch from neuronal to glial potential upon neurosphere amplification. Our data suggest that neurosphere formation does not expand the endogenous neurogenic NPCs but rather promotes amplification of gliogenic precursors that do not respond to niche-derived signals of cellular specification and differentiation.

  5. Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma.

    PubMed

    Xiong, Ye; Liu, Liyun; Zhu, Shuang; Zhang, Baole; Qin, Yuxia; Yao, Ruiqin; Zhou, Hao; Gao, Dian Shuai

    2017-02-12

    As the most prevalent primary brain tumor, gliomas are highly metastatic, invasive and are characteristic of high levels of glial cell-line derived neurotrophic factor (GDNF). GDNF is an important factor for invasive glioma cell growth; however, the underlying mechanism involved is unclear. In this study, we affirm a significantly higher expression of the precursor of N-cadherin (proN-cadherin) in most gliomas compared with normal brain tissues. Our findings reveal that GDNF interacts with the extracellular domain of proN-cadherin, which suggests that proN-cadherin mediates GDNF-induced glioma cell migration and invasion. We hypothesize that proN-cadherin might cause homotypic adhesion loss within neighboring cells and at the same time promote heterotypic adhesion within the extracellular matrix (ECM) through a certain mechanism. This study also demonstrates that the interaction between GDNF and proN-cadherin activates specific intracellular signaling pathways; furthermore, GDNF promoted the secretion of matrix metalloproteinase-9 (MMP-9), which degrades the ECM via proN-cadherin. To reach the future goal of developing novel therapies of glioma, this study, reveals a unique mechanism of glioma cell migration and invasion.

  6. ICV-transplanted human glial precursor cells are short-lived yet exert immunomodulatory effects in mice with EAE.

    PubMed

    Kim, Heechul; Walczak, Piotr; Muja, Naser; Campanelli, James T; Bulte, Jeff W M

    2012-07-01

    Human glial precursor cells (hGPs) have potential for remyelinating lesions and are an attractive cell source for cell therapy of multiple sclerosis (MS). To investigate whether transplanted hGPs can affect the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we evaluated the therapeutic effects of transplanted hGPs together with the in vivo fate of these cells using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). At 14 days post-EAE induction, mice (n = 19) were intracerebroventricularly (ICV) injected with 5 × 10(5) hGPs that were magnetically labeled with superparamagnetic iron oxide (SPIO) particles as MR contrast agent and transduced with firefly luciferase for BLI of cell survival. Control mice (n = 18) received phosphate buffered saline (PBS) vehicle only. The severity of EAE clinical disability in the hGP-transplanted group was significantly suppressed (P < 0.05) with concomitant inhibition of ConA and MOG-specific T cell proliferation in the spleen. Astrogliosis was reduced and a lower activity of macrophages and/or microglia was observed in the spinal cord (P < 0.05). On MRI, SPIO signal was detected within the lateral ventricle from 1 day post-transplantation and remained there for up to 34 days. BLI indicated that most cells did not survive beyond 5-10 days, consistent with the lack of detectable migration into the brain parenchyma and the histological presence of an abundance of apoptotic cells. Transplanted hGPs could not be detected in the spleen. We conclude that ICV transplantation of short-lived hGPs can have a remote therapeutic effect through immunomodulation from within the ventricle, without cells directly participating in remyelination.

  7. Oligodendrocyte Precursor Cells Modulate the Neuronal Network by Activity-Dependent Ectodomain Cleavage of Glial NG2

    PubMed Central

    Singh, Jeet; Frischknecht, Renato; Marongiu, Daniele; Binamé, Fabien; Perera, Sumudhu S.; Endres, Kristina; Lutz, Beat; Radyushkin, Konstantin; Trotter, Jacqueline; Mittmann, Thomas

    2014-01-01

    The role of glia in modulating neuronal network activity is an important question. Oligodendrocyte precursor cells (OPC) characteristically express the transmembrane proteoglycan nerve-glia antigen 2 (NG2) and are unique glial cells receiving synaptic input from neurons. The development of NG2+ OPC into myelinating oligodendrocytes has been well studied, yet the retention of a large population of synapse-bearing OPC in the adult brain poses the question as to additional functional roles of OPC in the neuronal network. Here we report that activity-dependent processing of NG2 by OPC-expressed secretases functionally regulates the neuronal network. NG2 cleavage by the α-secretase ADAM10 yields an ectodomain present in the extracellular matrix and a C-terminal fragment that is subsequently further processed by the γ-secretase to release an intracellular domain. ADAM10-dependent NG2 ectodomain cleavage and release (shedding) in acute brain slices or isolated OPC is increased by distinct activity-increasing stimuli. Lack of NG2 expression in OPC (NG2-knockout mice), or pharmacological inhibition of NG2 ectodomain shedding in wild-type OPC, results in a striking reduction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) in pyramidal neurons of the somatosensory cortex and alterations in the subunit composition of their α-amino-3-hydroxy-5-methyl-4-isoxazolepr opionicacid (AMPA) receptors. In NG2-knockout mice these neurons exhibit diminished AMPA and NMDA receptor-dependent current amplitudes; strikingly AMPA receptor currents can be rescued by application of conserved LNS protein domains of the NG2 ectodomain. Furthermore, NG2-knockout mice exhibit altered behavior in tests measuring sensorimotor function. These results demonstrate for the first time a bidirectional cross-talk between OPC and the surrounding neuronal network and demonstrate a novel physiological role for OPC in regulating information processing at neuronal synapses. PMID

  8. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    PubMed

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive.

  9. Glial Restricted Precursor Cell Transplant with Cyclic Adenosine Monophosphate Improved Some Autonomic Functions but Resulted in a Reduced Graft Size after Spinal Cord Contusion Injury in Rats

    PubMed Central

    Nout, Yvette S.; Culp, Esther; Schmidt, Markus H.; Tovar, C. Amy; Pröschel, Christoph; Mayer-Pröschel, Margot; Noble, Mark D.; Beattie, Michael S.; Bresnahan, Jacqueline C.

    2010-01-01

    Transplantation of glial restricted precursor (GRP) cells has been shown to reduce glial scarring after spinal cord injury (SCI) and, in combination with neuronal restricted precursor (NRP) cells or enhanced expression of neurotrophins, to improve recovery of function after SCI. We hypothesized that combining GRP transplants with rolipram and cAMP would improve functional recovery, similar to that seen after combining Schwann cell transplants with increasing cAMP. A short term study, 1)uninjured control, 2)SCI+vehicle, and 3)SCI+cAMP, showed that spinal cord [cAMP] were increased 14 days after SCI. We used 51 male rats subjected to a thoracic SCI for a 12-week survival study: 1)SCI+vehicle, 2)SCI+GRP, 3)SCI+cAMP, 4)SCI+GRP+cAMP, and 5)uninjured endpoint age-matched control (AM). Rolipram was administered for 2 weeks after SCI. At 9 days after SCI, GRP transplantation and injection of dibutyryl-cAMP into the spinal cord were performed. GRP cells survived, differentiated, and formed extensive transplants that were well integrated with host tissue. Presence of GRP cells increased the amount of tissue in the lesion; however, cAMP reduced the graft size. White matter sparing at the lesion epicenter was not affected. Serotonergic input to the lumbosacral spinal cord was not affected by treatment, but the amount of serotonin immediately caudal to the lesion was reduced in the cAMP groups. Using telemetric monitoring of corpus spongiosum penis pressure we show that the cAMP groups regained the same number of micturitions per 24 hrs when compared to the AM group, however, the frequency of peak pressures was increased in these groups compared to the AM group. In contrast, the GRP groups had similar frequency of peak pressures compared to baseline and the AM group. Animals that received GRP cells regained the same number of erectile events per 24 hrs compared to baseline and the AM group. Since cAMP reduced the GRP transplant graft, and some modest positive effects were seen

  10. Glial restricted precursor cell transplant with cyclic adenosine monophosphate improved some autonomic functions but resulted in a reduced graft size after spinal cord contusion injury in rats.

    PubMed

    Nout, Yvette S; Culp, Esther; Schmidt, Markus H; Tovar, C Amy; Pröschel, Christoph; Mayer-Pröschel, Margot; Noble, Mark D; Beattie, Michael S; Bresnahan, Jacqueline C

    2011-01-01

    Transplantation of glial restricted precursor (GRP) cells has been shown to reduce glial scarring after spinal cord injury (SCI) and, in combination with neuronal restricted precursor (NRP) cells or enhanced expression of neurotrophins, to improve recovery of function after SCI. We hypothesized that combining GRP transplants with rolipram and cAMP would improve functional recovery, similar to that seen after combining Schwann cell transplants with increasing cAMP. A short term study, (1) uninjured control, (2) SCI+vehicle, and (3) SCI+cAMP, showed that spinal cord [cAMP] was increased 14days after SCI. We used 51 male rats subjected to a thoracic SCI for a 12-week survival study: (1) SCI+vehicle, (2) SCI+GRP, (3) SCI+cAMP, (4) SCI+GRP+cAMP, and (5) uninjured endpoint age-matched control (AM). Rolipram was administered for 2weeks after SCI. At 9days after SCI, GRP transplantation and injection of dibutyryl-cAMP into the spinal cord were performed. GRP cells survived, differentiated, and formed extensive transplants that were well integrated with host tissue. Presence of GRP cells increased the amount of tissue in the lesion; however, cAMP reduced the graft size. White matter sparing at the lesion epicenter was not affected. Serotonergic input to the lumbosacral spinal cord was not affected by treatment, but the amount of serotonin immediately caudal to the lesion was reduced in the cAMP groups. Using telemetric monitoring of corpus spongiosum penis pressure we show that the cAMP groups regained the same number of micturitions per 24hours when compared to the AM group, however, the frequency of peak pressures was increased in these groups compared to the AM group. In contrast, the GRP groups had similar frequency of peak pressures compared to baseline and the AM group. Animals that received GRP cells regained the same number of erectile events per 24hours compared to baseline and the AM group. Since cAMP reduced the GRP transplant graft, and some modest positive

  11. Transplanted Glial Restricted Precursor Cells Improve Neurobehavioral and Neuropathological Outcomes in a Mouse Model of Neonatal White Matter Injury Despite Limited Cell Survival

    PubMed Central

    Porambo, Michael; Phillips, Andre W.; Marx, Joel; Ternes, Kylie; Arauz, Edwin; Pletnikov, Mikhail; Wilson, Mary Ann; Rothstein, Jeffery D.; Johnston, Michael V.; Fatemi, Ali

    2014-01-01

    Objective Neonatal White Matter Injury (NWMI) is the leading cause of cerebral palsy and other neurocognitive deficits in prematurely-born children, and no restorative therapies exist. Our objective was to determine the fate and effect of glial restricted precursor cell (GRP) transplantation in an ischemic mouse model of NWMI. Methods Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal-day 5 (P5). At P22, intracallosal injections of either eGFP+ GRPs or saline were performed in control and ligated mice. Neurobehavioral and postmortem studies were performed at four and eight weeks post-transplantation. Results GRP survival was comparable at one month but significantly lower at two months post-transplantation in NWMI mice compared to unligated controls. Surviving cells showed better migration capability in controls; however, the differentiation capacity of transplanted cells was similar in control and NWMI. Saline-treated NWMI mice showed significantly altered response in startle amplitude and pre-pulse inhibition paradigms compared to unligated controls, while these behavioral tests were completely normal in GRP-transplanted animals. Similarly, there was significant increase in hemispheric myelin basic protein density, along with significant decrease in pathologic axonal staining in cell-treated NWMI mice compared to saline-treated NWMI animals. Interpretation The Reduced long-term survival and migration of transplanted GRPs in an ischemia-induced NWMI model suggests that neonatal ischemia leads to long-lasting detrimental effects on oligodendroglia even months after the initial insult. Despite limited GRP-survival, behavioral and neuropathological outcomes were improved after GRP-transplantation. Our results suggest that exogenous GRPs improve myelination through trophic effects in addition to differentiation into mature oligodendrocytes. PMID:25377280

  12. Targeting glial physiology and glutamate cycling in the treatment of depression

    PubMed Central

    Valentine, Gerald W.; Sanacora, Gerard

    2009-01-01

    Accumulating evidence indicates that dysfunction in amino acid neurotransmission contributes to the pathophysiology of depression. Consequently, the modulation of amino acid neurotransmission represents a new strategy for antidepressant development. While glutamate receptor ligands are known to have antidepressant effects, mechanisms regulating glutamate cycling and metabolism may be viable drug targets as well. In particular, excitatory amino acid transporters (EAATs) that are embedded in glial processes constitute the primary means of clearing extrasynaptic glutamate. Therefore, the decreased glial number observed in preclinical stress models, and in postmortem tissue from depressed patients provides intriguing, yet indirect evidence for a role of disrupted glutamate homeostasis in the pathophysiology of depression. More direct evidence for this hypothesis comes from studies using magnetic resonance spectroscopy (MRS), a technique that non-invasively measures in vivo concentrations of glutamate and other amino acids under different experimental conditions. Furthermore, when combined with the infusion of 13C-labeled metabolic precursors, MRS can measure flux through discrete metabolic pathways. This approach has recently shown that glial amino acid metabolism is reduced by chronic stress, an effect that provides a link between environmental stress and the decreased EAAT activity observed under conditions of increased oxidative stress in the brain. Furthermore, administration of riluzole, a drug that enhances glutamate uptake through EAATs, reversed this stress-induced change in glial metabolism. Because riluzole has antidepressant effects in both animal models and human subjects, it may represent the prototype for a novel class of antidepressants with the modulation of glial physiology as a primary mechanism of action. PMID:19376090

  13. Glial cell dysregulation: a new perspective on Alzheimer disease.

    PubMed

    von Bernhardi, Rommy

    2007-12-01

    Alzheimer disease (AD) is a major cause of dementia. Several mechanisms have been postulated to explain its pathogenesis, beta-amyloid (A beta toxicity, cholinergic dysfunction, Tau hyper-phosphorylation, oxidative damage, synaptic dysfunction and inflammation secondary to senile plaques, among others. Glial cells are the major producers of inflammatory mediators, and cytotoxic activation of glial cells is linked to several neurodegenerative diseases; however, whether inflammation is a consequence or the cause of neurodegeneration is still unclear. I propose that inflammation and cellular stress associated with aging are key events in the development of AD through the induction of glial dysfunction. Dysregulated inflammatory response can elicit glial cell activation by compounds which are normally poorly reactive. Inflammation can also be the major cause of defective handling of A beta and the amyloid precursor protein (APP). Here I review evidence that support the proposal that dysfunctional glia and the resulting neuroinflammation can explain many features of AD. Evidence supports the notion that damage caused by inflammation is not only a primary cause of neurodegeneration but also an inducer for the accumulation of A beta in AD. Dysfunctional glia can result in impaired neuronal function in AD, as well as in many progressive neurodegenerative disorders. We show that microglial cell activation is enhanced under pro-inflammatory conditions, indicating that glial cell responses to A beta related proteins can be critically dependent on the priming of glial cells by pro-inflammatory factors.

  14. Clear & Simple

    MedlinePlus

    ... the audience themselves. It is important to get direct audience involvement at some point to test the ... words are defined clearly. Sentences are simple, specific, direct, and written in the active voice. Each idea ...

  15. The scoop on the fly brain: glial engulfment functions in Drosophila.

    PubMed

    Logan, Mary A; Freeman, Marc R

    2007-02-01

    Glial cells provide support and protection for neurons in the embryonic and adult brain, mediated in part through the phagocytic activity of glia. Glial cells engulf apoptotic cells and pruned neurites from the developing nervous system, and also clear degenerating neuronal debris from the adult brain after neural trauma. Studies indicate that Drosophila melanogaster is an ideal model system to elucidate the mechanisms of engulfment by glia. The recent studies reviewed here show that many features of glial engulfment are conserved across species and argue that work in Drosophila will provide valuable cellular and molecular insight into glial engulfment activity in mammals.

  16. Modeling cognition and disease using human glial chimeric mice.

    PubMed

    Goldman, Steven A; Nedergaard, Maiken; Windrem, Martha S

    2015-08-01

    As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear that transplanted hGPCs not only engraft and expand within murine hosts, but dynamically outcompete the resident progenitors so as to ultimately dominate the host brain. The engrafted human progenitor cells proceed to generate parenchymal astrocytes, and when faced with a hypomyelinated environment, oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human neurological and neuropsychiatric disease.

  17. Central neuron-glial and glial-glial interactions following axon injury.

    PubMed

    Aldskogius, H; Kozlova, E N

    1998-05-01

    Axon injury rapidly activates microglial and astroglial cells close to the axotomized neurons. Following motor axon injury, astrocytes upregulate within hour(s) the gap junction protein connexin-43, and within one day glial fibrillary acidic protein (GFAP). Concomitantly, microglial cells proliferate and migrate towards the axotomized neuron perikarya. Analogous responses occur in central termination territories of peripherally injured sensory ganglion cells. The activated microglia express a number of inflammatory and immune mediators. When neuron degeneration occurs, microglia act as phagocytes. This is uncommon after peripheral nerve injury in the adult mammal, however, and the functional implications of the glial cell responses in this situation are unclear. When central axons are injured, the glial cell responses around the affected neuron perikarya appears to be minimal or absent, unless neuron degeneration occurs. Microglia proliferate, and astrocytes upregulate GFAP along central axons undergoing anterograde, Wallerian, degeneration. Although microglia develop into phagocytes, they eliminate the disintegrating myelin very slowly, presumably because they fail to release molecules which facilitate phagocytosis. During later stages of Wallerian degeneration, oligodendrocytes express clusterin, a glycoprotein implicated in several conditions of cell degeneration. A hypothetical scheme for glial cell activation following axon injury is discussed, implying the injured neurons initially interact with adjacent astrocytes. Subsequently, neighbouring resting microglia are activated. These glial reactions are amplified by paracrine and autocrine mechanisms, in which cytokines appear to be important mediators. The specific functional properties of the activated glial cells will determine their influence on neuronal survival, axon regeneration, and synaptic plasticity. The control of the induction and progression of these responses are therefore likely to be critical

  18. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate.

    PubMed Central

    Tsacopoulos, M; Evêquoz-Mercier, V; Perrottet, P; Buchner, E

    1988-01-01

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[3H]glucose convert this glucose analogue to 2-deoxy[3H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system. Images PMID:3186756

  19. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

    SciTech Connect

    Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

    1988-11-01

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy(/sup 3/H)glucose convert this glucose analogue to 2-deoxy(/sup 3/H)glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O/sub 2/ and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system.

  20. [Glial activation and brain aging].

    PubMed

    Sugaya, K

    2001-10-01

    While basal forebrain cholinergic neurons degenerate in aging and Alzheimer's disease, the cholinergic groups of the upper brainstem are preserved. Since the brainstem reticular-like cholinergic neurons differ from the rostral cholinergic phenotype by their high expression of nitric oxide synthase (NOS) mRNA, we hypothesized that they contain biochemical mechanisms to protect themselves against self-induced damage by nitric oxide (NO). Our initial question was a source of the NO during the aging process. We found a significant correlation between cognitive function and markers for glial activation and oxidative stress using aged rats. This result indicates that oxidative stress accompanied by glial activation may be occurred in the cognitively impaired animals. We also found mitochondrial DNA (mDNA) was significantly damaged in these animals, while accumulation of oxidative damage was not evident in other molecules. Therefore, oxidative damage to the mDNA by glial activation may occur in the cells having poor protection against oxidative stress during aging. Then the dysfunction of mitochondria, induced by the mDNA damage, may induce cell death as well as produce another oxidative stress to cause neuronal damage. The damaged neurons induce further glial activation and such self-accelerated immune-like response results in progressive neurodegeneration.

  1. GLIAL RESPONSES AFTER CHORDA TYMPANI NERVE INJURY

    PubMed Central

    Bartel, Dianna L.

    2013-01-01

    The chorda tympani (CT) nerve innervates lingual taste buds and is susceptible to damage during dental and inner ear procedures. Interruption of the CT results in a disappearance of taste buds, which can be accompanied by taste disturbances. Because the CT usually regenerates to reinnervate taste buds successfully in a few weeks, a persistence of taste disturbances may indicate alterations in central nervous function. Peripheral injury to other sensory nerves leads to glial responses at central terminals, which actively contribute to abnormal sensations arising from nerve damage. Therefore, the current study examined microglial and astrocytic responses in the first central gustatory relay -the nucleus of the solitary tract (nTS)- after transection of the CT. Damage to the CT resulted in significant microglial responses in terms of morphological reactivity and an increased density of microglial cells from 2-20 days after injury. This increased microglial population primarily resulted from microglial proliferation from 1.5-3 days, which was supplemented by microglial migration within sub-divisions of the nTS between days 2-3. Unlike other nerve injuries, CT injury did not result in recruitment of bone marrow-derived precursors. Astrocytes also reacted in the nTS with increased levels of GFAP by 3 days, although none showed evidence of cell division. GFAP levels remained increased at 30 days by which time microglial responses had resolved. These results show that nerve damage to the CT results in central glial responses, which may participate in long lasting taste alterations following CT lesion. PMID:22315167

  2. Glial cells and energy balance.

    PubMed

    Argente-Arizón, Pilar; Guerra-Cantera, Santiago; Garcia-Segura, Luis Miguel; Argente, Jesús; Chowen, Julie A

    2017-01-01

    The search for new strategies and drugs to abate the current obesity epidemic has led to the intensification of research aimed at understanding the neuroendocrine control of appetite and energy expenditure. This intensified investigation of metabolic control has also included the study of how glial cells participate in this process. Glia, the most abundant cell type in the central nervous system, perform a wide spectrum of functions and are vital for the correct functioning of neurons and neuronal circuits. Current evidence indicates that hypothalamic glia, in particular astrocytes, tanycytes and microglia, are involved in both physiological and pathophysiological mechanisms of appetite and metabolic control, at least in part by regulating the signals reaching metabolic neuronal circuits. Glia transport nutrients, hormones and neurotransmitters; they secrete growth factors, hormones, cytokines and gliotransmitters and are a source of neuroprogenitor cells. These functions are regulated, as glia also respond to numerous hormones and nutrients, with the lack of specific hormonal signaling in hypothalamic astrocytes disrupting metabolic homeostasis. Here, we review some of the more recent advances in the role of glial cells in metabolic control, with a special emphasis on the differences between glial cell responses in males and females.

  3. Methylphenidate Increases Glutamate Uptake in Bergmann Glial Cells.

    PubMed

    Guillem, Alain M; Martínez-Lozada, Zila; Hernández-Kelly, Luisa C; López-Bayghen, Esther; López-Bayghen, Bruno; Calleros, Oscar A; Campuzano, Marco R; Ortega, Arturo

    2015-11-01

    Glutamate, the main excitatory transmitter in the vertebrate brain, exerts its actions through the activation of specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of glutamate uptake systems, mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing an excessive glutamatergic stimulation and thus neuronal damage. Autism spectrum disorders comprise a group of syndromes characterized by impaired social interactions and anxiety. One or the most common drugs prescribed to treat these disorders is Methylphenidate, known to increase dopamine extracellular levels, although it is not clear if its sedative effects are related to a plausible regulation of the glutamatergic tone via the regulation of the glial glutamate uptake systems. To gain insight into this possibility, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity and protein levels of glutamate transporters was detected upon Methylphenidate exposure. Interestingly, this increase is the result of an augmentation of both the synthesis as well as the insertion of these protein complexes in the plasma membrane. These results favour the notion that glial cells are Methylphenidate targets, and that by these means could regulate dopamine turnover.

  4. Review: Glial lineages and myelination in the central nervous system

    PubMed Central

    COMPSTON, ALASTAIR; ZAJICEK, JOHN; SUSSMAN, JON; WEBB, ANNA; HALL, GILLIAN; MUIR, DAVID; SHAW, CHRISTOPHER; WOOD, ANDREW; SCOLDING, NEIL

    1997-01-01

    Oligodendrocytes, derived from stem cell precursors which arise in subventricular zones of the developing central nervous system, have as their specialist role the synthesis and maintenance of myelin. Astrocytes contribute to the cellular architecture of the central nervous system and act as a source of growth factors and cytokines; microglia are bone-marrow derived macrophages which function as primary immunocompetent cells in the central nervous system. Myelination depends on the establishment of stable relationships between each differentiated oligodendrocyte and short segments of several neighbouring axons. There is growing evidence, especially from studies of glial cell implantation, that oligodendrocyte precursors persist in the adult nervous system and provide a limited capacity for the restoration of structure and function in myelinated pathways damaged by injury or disease. PMID:9061442

  5. Glial dysfunction in abstinent methamphetamine abusers.

    PubMed

    Sailasuta, Napapon; Abulseoud, Osama; Harris, Kent C; Ross, Brian D

    2010-05-01

    Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized (13)C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial (13)C-bicarbonate production rate from [1-(13)C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 micromol/g per min (N=5) versus controls 0.11 micromol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous (13)C MRS methods may determine 'cause and effect' between glial failure and neuronal injury.

  6. Phenotypic changes in satellite glial cells in cultured trigeminal ganglia.

    PubMed

    Belzer, Vitali; Shraer, Nathanael; Hanani, Menachem

    2010-11-01

    Satellite glial cells (SGCs) are specialized cells that form a tight sheath around neurons in sensory ganglia. In recent years, there is increasing interest in SGCs and they have been studied in both intact ganglia and in tissue culture. Here we studied phenotypic changes in SGCs in cultured trigeminal ganglia from adult mice, containing both neurons and SGCs, using phase optics, immunohistochemistry and time-lapse photography. Cultures were followed for up to 14 days. After isolation virtually every sensory neuron is ensheathed by SGCs, as in the intact ganglia. After one day in culture, SGCs begin to migrate away from their parent neurons, but in most cases the neurons still retain an intact glial cover. At later times in culture, there is a massive migration of SGCs away from the neurons and they undergo clear morphological changes, and at 7 days they become spindle-shaped. At one day in culture SGCs express the glial marker glutamine synthetase, and also the purinergic receptor P2X7. From day 2 in culture the glutamine synthetase expression is greatly diminished, whereas that of P2X7 is largely unchanged. We conclude that SGCs retain most of their characteristics for about 24 h after culturing, but undergo major phenotypic changes at later times.

  7. Tramtrack controls glial number and identity in the Drosophila embryonic CNS.

    PubMed

    Badenhorst, P

    2001-10-01

    Neurons and glia are often derived from common multipotent stem cells. In Drosophila, neural identity appears to be the default fate of these precursors. Stem cells that generate either neurons or glia transiently express neural stem cell-specific markers. Further development as glia requires the activation of glial-specific regulators. However, this must be accompanied by simultaneous repression of the alternate neural fate. I show that the Drosophila transcriptional repressor Tramtrack is a key repressor of neuronal fates. It is expressed at high levels in all mature glia of the embryonic central nervous system. Analysis of the temporal profile of Tramtrack expression in glia shows that it follows that of existing glial markers. When expressed ectopically before neural stem cell formation, Tramtrack represses the neural stem cell-specific genes asense and deadpan. Surprisingly, Tramtrack protein levels oscillate in a cell cycle-dependent manner in proliferating glia, with expression dropping before replication, but re-initiating after S phase. Overexpression of Tramtrack blocks glial development by inhibiting S-phase and repressing expression of the S-phase cyclin, cyclin E. Conversely, in tramtrack mutant embryos, glia are disrupted and undergo additional rounds of replication. I propose that Tramtrack ensures stable mature glial identity by both repressing neuroblast-specific genes and controlling glial cell proliferation.

  8. Connexin-deficiency affects expression levels of glial glutamate transporters within the cerebrum.

    PubMed

    Unger, Tina; Bette, Stefanie; Zhang, Jiong; Theis, Martin; Engele, Jürgen

    2012-01-06

    The glial glutamate transporter subtypes, GLT-1/EAAT-2 and GLAST/EAAT-1 clear the bulk of extracellular glutamate and are severely dysregulated in various acute and chronic brain diseases. Despite the previous identification of several extracellular factors modulating glial glutamate transporter expression, our knowledge of the regulatory network controlling glial glutamate transport in health and disease still remains incomplete. In studies with cultured cortical astrocytes, we previously obtained evidence that glial glutamate transporter expression is also affected by gap junctions/connexins. To assess whether gap junctions would likewise control the in vivo expression of glial glutamate transporters, we have now assessed their expression levels in brains of conditional Cx43 knockout mice, total Cx30 knockouts, as well as Cx43/Cx30 double knockouts. We found that either knocking out Cx30, Cx43, or both increases GLT-1/EAAT-2 protein levels in the cerebral cortex to a similar extent. By contrast, GLAST/EAAT-1 protein levels maximally increased in cerebral cortices of Cx30/Cx43 double knockouts, implying that gap junctions differentially affect the expression of GLT-1/EAAT-2 and GLAST/EAAT-1. Quantitative PCR analysis further revealed that increases in glial glutamate transporter expression are brought about by transcriptional and translational/posttranslational processes. Moreover, GLT-1/EAAT-2- and GLAST/EAAT-1 protein levels remained unchanged in the hippocampi of Cx43/Cx30 double knockouts when compared to Cx43fl/fl controls, indicating brain region-specific effects of gap junctions on glial glutamate transport. Since astrocytic gap junction coupling is affected in various forms of brain injuries, our findings point to gap junctions/connexins as important regulators of glial glutamate turnover in the diseased cerebral cortex.

  9. Social Behavior in Medulloblastoma: Functional Analysis of Tumor-Supporting Glial Cells

    DTIC Science & Technology

    2015-10-01

    neuron precursors (GNPs) in developing cerebellum proliferate exponentially , and the misregulation of which has been linked to medulloblastoma formation...sustains the tumor growth . In the past year, we have completed most of the work proposed in aim 1. Our data showed that the glial-ablation treatment not...cerebellum proliferate exponentially . The misregulation of GNP proliferation has been linked to medulloblastoma formation. Fate mapping experiments

  10. The interface between glial progenitors and gliomas

    PubMed Central

    Canoll, Peter

    2009-01-01

    The mammalian brain and spinal cord contain heterogeneous populations of cycling, immature cells. These include cells with stem cell-like properties as well as progenitors in various stages of early glial differentiation. This latter population is distributed widely throughout gray and white matter and numerically represents an extremely large cell pool. In this review, we discuss the possibility that the glial progenitors that populate the adult CNS are one source of gliomas. Indeed, the marker phenotypes, morphologies, and migratory properties of cells in gliomas strongly resemble glial progenitors in many ways. We review briefly some salient features of normal glial development and then examine the similarities and differences between normal progenitors and cells in gliomas, focusing on the phenotypic plasticity of glial progenitors and the responses to growth factors in promoting proliferation and migration of normal and glioma cells, and discussing known mutational changes in gliomas in the context of how these might affect the proliferative and migratory behaviors of progenitors. Finally, we will discuss the “cancer stem cell” hypothesis in light of the possibility that glial progenitors can generate gliomas. PMID:18784926

  11. Glial Progenitors as Targets for Transformation in Glioma

    PubMed Central

    Ilkanizadeh, Shirin; Lau, Jasmine; Huang, Miller; Foster, Daniel J.; Wong, Robyn; Frantz, Aaron; Wang, Susan; Weiss, William A.; Persson, Anders I.

    2014-01-01

    Glioma is the most common primary malignant brain tumor and arises throughout the central nervous system (CNS). Recent focus on stem-like glioma cells has implicated neural stem cells (NSCs), a minor precursor population restricted to germinal zones, as a potential source of gliomas. In this review, we will focus on the relationship between oligodendrocyte progenitor cells (OPCs), the largest population of cycling glial progenitors in the postnatal brain, and gliomas. Recent studies suggest that OPCs can give rise to gliomas. Furthermore, signaling pathways often associated with NSCs also play key roles during OPC lineage development. Recent advances suggesting that gliomas can undergo a switch from progenitor- to stem-like phenotype after therapy, implicating that an OPC-origin is more likely than previously recognized. Future in-depth studies of OPC biology may shed light on the etiology of OPC-derived gliomas and reveal new therapeutic avenues. PMID:24889528

  12. Glial chain migration requires pioneer cells.

    PubMed

    Aigouy, Benoît; Lepelletier, Léa; Giangrande, Angela

    2008-11-05

    The migration of glial chains along the nerve entails directional and coordinated movement. Despite its importance in the formation of the nervous system, this process remains poorly understood, because of the difficulty of manipulating identified cells. Using confocal time-lapse and cell ablation in the whole animal, we provide direct evidence for a discrete number of Drosophila peripheral glial cells acting as pioneers and guiding the rest of the migratory chain. These cells are in direct contact with several follower cells through a very long and stable cytoplasmic extension. The presence of pioneer cells and homotypic interactions at the tip of the chain allows coordinated movement and the formation of a continuous sheath around the nerve. These in vivo data open novel perspectives for understanding the cellular bases of vertebrate glial migration in physiological and pathological conditions.

  13. The hypoparathyroidism-associated mutation in Drosophila Gcm compromises protein stability and glial cell formation

    PubMed Central

    Xi, Xiao; Lu, Lu; Zhuge, Chun-Chun; Chen, Xuebing; Zhai, Yuanfen; Cheng, Jingjing; Mao, Haian; Yang, Chang-Ching; Tan, Bertrand Chin-Ming; Lee, Yi-Nan; Chien, Cheng-Ting; Ho, Margaret S.

    2017-01-01

    Differentiated neurons and glia are acquired from immature precursors via transcriptional controls exerted by factors such as proteins in the family of Glial Cells Missing (Gcm). Mammalian Gcm proteins mediate neural stem cell induction, placenta and parathyroid development, whereas Drosophila Gcm proteins act as a key switch to determine neuronal and glial cell fates and regulate hemocyte development. The present study reports a hypoparathyroidism-associated mutation R59L that alters Drosophila Gcm (Gcm) protein stability, rendering it unstable, and hyperubiquitinated via the ubiquitin-proteasome system (UPS). GcmR59L interacts with the Slimb-based SCF complex and Protein Kinase C (PKC), which possibly plays a role in its phosphorylation, hence altering ubiquitination. Additionally, R59L causes reduced Gcm protein levels in a manner independent of the PEST domain signaling protein turnover. GcmR59L proteins bind DNA, functionally activate transcription, and induce glial cells, yet at a less efficient level. Finally, overexpression of either wild-type human Gcmb (hGcmb) or hGcmb carrying the conserved hypoparathyroidism mutation only slightly affects gliogenesis, indicating differential regulatory mechanisms in human and flies. Taken together, these findings demonstrate the significance of this disease-associated mutation in controlling Gcm protein stability via UPS, hence advance our understanding on how glial formation is regulated. PMID:28051179

  14. dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation.

    PubMed

    Tavares, Lígia; Correia, Andreia; Santos, Marília A; Relvas, João B; Pereira, Paulo S

    2017-03-01

    In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-β signalling activation.

  15. dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation

    PubMed Central

    Correia, Andreia; Santos, Marília A.; Relvas, João B.; Pereira, Paulo S.

    2017-01-01

    In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-β signalling activation. PMID:28267791

  16. Calcineurin and glial signaling: neuroinflammation and beyond.

    PubMed

    Furman, Jennifer L; Norris, Christopher M

    2014-09-10

    Similar to peripheral immune/inflammatory cells, neuroglial cells appear to rely on calcineurin (CN) signaling pathways to regulate cytokine production and cellular activation. Several studies suggest that harmful immune/inflammatory responses may be the most impactful consequence of aberrant CN activity in glial cells. However, newly identified roles for CN in glutamate uptake, gap junction regulation, Ca2+ dyshomeostasis, and amyloid production suggest that CN's influence in glia may extend well beyond neuroinflammation. The following review will discuss the various actions of CN in glial cells, with particular emphasis on astrocytes, and consider the implications for neurologic dysfunction arising with aging, injury, and/or neurodegenerative disease.

  17. DNA damage, neuronal and glial cell death and neurodegeneration.

    PubMed

    Barzilai, Ari

    2010-11-01

    The DNA damage response (DDR) is a key factor in the maintenance of genome stability. As such, it is a central axis in sustaining cellular homeostasis in a variety of contexts: development, growth, differentiation, and maintenance of the normal life cycle of the cell. It is now clear that diverse mechanisms encompassing cell cycle regulation, repair pathways, many aspects of cellular metabolism, and cell death are inter-linked and act in concert in response to DNA damage. Defects in the DDR in proliferating cells can lead to cancer, while DDR defects in neurons may result in neurodegeneration. Mature neurons are highly differentiated, post-mitotic cells that cannot be replenished after disease or trauma. Their high metabolic activity generates large amounts of reactive oxygen species with DNA damaging capacity. Moreover, their intense transcriptional activity increases the potential for genomic DNA damage. Respectively, neurons have elaborate mechanisms to defend the integrity of their genome, thus ensuring their longevity and functionality in the face of these threats. Over the course of the past two decades, there has been a substantial increase in our understanding of the role of glial cells in supporting the neuronal cell DDR and longevity. This review article focuses on the potential role of the DDR in the etiology and pathogenesis of neurodegenerative diseases, and in addition, it describes various aspects of glial cell functionality in two genomic instability disorders: ataxia telangiectasia (A-T) and Nijmegen breakage syndrome.

  18. Predetermined embryonic glial cells form the distinct glial sheaths of the Drosophila peripheral nervous system.

    PubMed

    von Hilchen, Christian M; Bustos, Alvaro E; Giangrande, Angela; Technau, Gerhard M; Altenhein, Benjamin

    2013-09-01

    One of the numerous functions of glial cells in Drosophila is the ensheathment of neurons to isolate them from the potassium-rich haemolymph, thereby establishing the blood-brain barrier. Peripheral nerves of flies are surrounded by three distinct glial cell types. Although all embryonic peripheral glia (ePG) have been identified on a single-cell level, their contribution to the three glial sheaths is not known. We used the Flybow system to label and identify each individual ePG in the living embryo and followed them into third instar larva. We demonstrate that all ePG persist until the end of larval development and some even to adulthood. We uncover the origin of all three glial sheaths and describe the larval differentiation of each peripheral glial cell in detail. Interestingly, just one ePG (ePG2) exhibits mitotic activity during larval stages, giving rise to up to 30 glial cells along a single peripheral nerve tract forming the outermost perineurial layer. The unique mitotic ability of ePG2 and the layer affiliation of additional cells were confirmed by in vivo ablation experiments and layer-specific block of cell cycle progression. The number of cells generated by this glial progenitor and hence the control of perineurial hyperplasia correlate with the length of the abdominal nerves. By contrast, the wrapping and subperineurial glia layers show enormous hypertrophy in response to larval growth. This characterisation of the embryonic origin and development of each glial sheath will facilitate functional studies, as they can now be addressed distinctively and genetically manipulated in the embryo.

  19. Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury

    PubMed Central

    Logan, Mary A.; Hackett, Rachel; Doherty, Johnna; Sheehan, Amy; Speese, Sean D.; Freeman, Marc R.

    2012-01-01

    Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function, and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial reponses to axon injury are molecularly encoded by unique isoforms of the Drosophila engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Draper-II, an alternative splice variant, potently inhibits glial engulfment function. Draper-II suppresses Draper-I signaling through a novel immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain and the tyrosine phosphatase Corkscrew (Csw). Intriguingly, loss of Draper-II/Csw signaling prolongs expression of glial engulfment genes after axotomy and reduces the ability of glia to respond to secondary axotomy. Our work highlights a novel role for Draper-II in inhibiting glial responses to neurodegeneration, and indicates a balance of opposing Draper-I/-II signaling events is essential to maintain glial sensitivity to brain injury. PMID:22426252

  20. Intrathoracic glial implants in a child with gliomatosis peritonei.

    PubMed

    Lipskar, Aaron M; Rothstein, David H; Soffer, Samuel Z; Edelman, Morris; Glick, Richard D

    2009-09-01

    Glial peritoneal implants, commonly referred to as gliomatosis peritonei, are an occasional feature of ovarian teratomas. They are benign nodules of mature glial tissue and usually do not adversely affect outcome. We present the case of a 12-year-old girl who underwent excision of an immature ovarian teratoma, along with biopsies of multiple glial peritoneal implants. She also had a 2-cm right-sided pleural mass, which turned out to be normal glial tissue that was histologically indistinguishable from the peritoneal glial tissue. Pleural gliomatosis has not been described in the literature. The pathophysiology of gliomatosis peritonei was originally thought to be the direct extrusion or lymphatic spread of glial cells from the associated teratoma, although it has been postulated that the glial implants may instead be the result of pluripotent Mullerian stem cells that undergo metaplasia. This report provides evidence to bolster the metaplastic theory.

  1. Diet - clear liquid

    MedlinePlus

    ... Group. Clear liquid diet. In: Morrison. Manual of Clinical Nutrition Management. Updated 2013. bscn2k15.weebly.com/uploads/1/2/9/2/12924787/manual_of_clinical_nutrition2013.pdf . Accessed August 20, 2016. Schattner MA, ...

  2. Clear cell unicystic ameloblastoma

    PubMed Central

    Radhika, MB; Thambiah, Lalita J; Paremala, K; Sudhakara, M

    2011-01-01

    Clear cell differentiation in unicystic ameloblastoma with inclusion of many other histologic variants in the same tumor is a very rare occurrence. Here, we report a case of a well-circumscribed large mandibular swelling in a 22 - year old female. The lesion was histopathologically diagnosed as unicystic ameloblastoma which showed multiple histologic patterns and clear cell differentiation. The tumor was treated with surgical enucleation and chemical cauterization. A follow up of 20 months has shown no recurrence after initial surgery. PMID:21731291

  3. Glial Cell Development and Function in Zebrafish

    PubMed Central

    Lyons, David A.; Talbot, William S.

    2015-01-01

    The zebrafish is a premier vertebrate model system that offers many experimental advantages for in vivo imaging and genetic studies. This review provides an overview of glial cell types in the central and peripheral nervous system of zebrafish. We highlight some recent work that exploited the strengths of the zebrafish system to increase the understanding of the role of Gpr126 in Schwann cell myelination and illuminate the mechanisms controlling oligodendrocyte development and myelination. We also summarize similarities and differences between zebrafish radial glia and mammalian astrocytes and consider the possibility that their distinct characteristics may represent extremes in a continuum of cell identity. Finally, we focus on the emergence of zebrafish as a model for elucidating the development and function of microglia. These recent studies have highlighted the power of the zebrafish system for analyzing important aspects of glial development and function. PMID:25395296

  4. White Matter Glial Pathology in Autism

    DTIC Science & Technology

    2014-09-01

    The majority of total nuclear-encoded non-ribosomal RNA in a human cell is “ dark matter ” un-annotated RNA. BMC Biol. 8, 149 (2010). 9. Ginsberg, S...DATE September 2014 2. REPORT TYPE Annual 3. DATES COVERED 1 Sep 2013 - 31 Aug 2014 4. TITLE AND SUBTITLE White Matter Glial Pathology in...stages of preparation due to poor sample quality factors such as low RIN or insufficient sequencing reads. Superficial white matter was laser

  5. Human brain glial cells synthesize thrombospondin.

    PubMed Central

    Asch, A S; Leung, L L; Shapiro, J; Nachman, R L

    1986-01-01

    Thrombospondin, a 450-kDa multinodular glycoprotein with lectin-type activity, is found in human platelets, endothelial cells, fibroblasts, smooth muscle cells, monocytes, and granular pneumocytes. Thrombospondin interacts with heparin, fibrinogen, fibronectin, collagen, histidine-rich glycoprotein, and plasminogen. Recently, thrombospondin synthesis by smooth muscle cells has been reported to be augmented by platelet-derived growth factor. We present evidence that thrombospondin is present within and synthesized by astrocytic neuroglial cells. Heparin-Sepharose affinity chromatography of material derived from a human brain homogenate yielded a protein that, when reduced, had an apparent size of 180 kDa and comigrated with reduced platelet thrombospondin on NaDodSO4/PAGE. Immunoblot analysis with monospecific anti-thrombospondin confirmed the presence of immunoreactive thrombospondin. Indirect immunofluorescence of cultured human glial cells indicated the presence of thrombospondin. Metabolic labeling of glial cell cultures with [35S]methionine followed by immunoprecipitation with monospecific anti-thrombospondin revealed synthesis of a 180-kDa polypeptide that comigrated with platelet thrombospondin on NaDodSO4/PAGE. Cultured human glial cells were incubated for 48 hr in serum-free medium with purified platelet-derived growth factor at concentrations up to 50 ng/ml. Aliquots taken at intervals were analyzed by a quantitative double-antibody ELISA. The growth factor stimulated the release of thrombospondin into the culture medium by as much as 10-fold over control cultures. The presence of thrombospondin within glial cells of the central nervous system and the augmentation of its synthesis by platelet-derived growth factor suggest that thrombospondin may play an important role in regulating cell-cell and cell-matrix interactions during periods of cell division and growth. Images PMID:2939460

  6. Physiological Functions of Glial Cell Hemichannels.

    PubMed

    Orellana, Juan A

    2016-01-01

    The brain performs exceptionally complex and dynamic tasks that depend on the coordinated interaction of neurons, glial cells, endothelial cells, pericytes, smooth muscle cells, ependymal cells, and circulating blood cells. Among these cells, glial cells have emerged as crucial protagonists in the regulation of synaptic transmission and neural function. Indeed, these cells express a wide range of receptors that enable them to sense changes in neuronal activity and the microenvironment by responding locally via the release of bioactive molecules known as gliotransmitters. In the central nervous system (CNS), a novel mechanism that allows gliotransmission via the opening of hemichannels has been proposed. These channels are composed of six protein subunits consisting of connexins or pannexins, which are two highly conserved protein families that are encoded by 21 and 3 genes, respectively, in humans. Typically, glial cell hemichannels exhibit low levels of activity, but this activity is sufficient to ensure the release of a broad spectrum of gliotransmitters, including ATP, D-serine, glutamate, adenosine, and glutathione. Here, we briefly review the current findings regarding the effects of the hemichannel-dependent release of gliotransmitters on the physiology of the CNS.

  7. Glial Cell Contributions to Auditory Brainstem Development

    PubMed Central

    Cramer, Karina S.; Rubel, Edwin W

    2016-01-01

    Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms. Several classes of glial cells, including astrocytes, oligodendrocytes and microglia, have now been explored in these circuits in both avian and mammalian brainstems. Distinct populations of astrocytes are found over the course of auditory brainstem maturation. Early appearing astrocytes are associated with spatial compartments in the avian auditory brainstem. Factors from late appearing astrocytes promote synaptogenesis and dendritic maturation, and astrocytes remain integral parts of specialized auditory synapses. Oligodendrocytes play a unique role in both birds and mammals in highly regulated myelination essential for proper timing to decipher interaural cues. Microglia arise early in brainstem development and may contribute to maturation of auditory pathways. Together these studies demonstrate the importance of non-neuronal cells in the assembly of specialized auditory brainstem circuits. PMID:27818624

  8. Clarifying Tissue Clearing

    PubMed Central

    Richardson, Douglas S.; Lichtman, Jeff W.

    2015-01-01

    Summary Biological specimens are intrinsically three dimensional; however because of the obscuring effects of light scatter, imaging deep into a tissue volume is problematic. Although efforts to eliminate the scatter by “clearing” the tissue have been ongoing for over a century, there have been a large number of recent innovations. This review introduces the physical basis for light-scatter in tissue, describes the mechanisms underlying various clearing techniques, and discusses several of the major advances in light microscopy for imaging cleared tissue. PMID:26186186

  9. Effect of treatment with choline alphoscerate on hippocampus microanatomy and glial reaction in spontaneously hypertensive rats.

    PubMed

    Tomassoni, Daniele; Avola, Roberto; Mignini, Fiorenzo; Parnetti, Lucilla; Amenta, Francesco

    2006-11-20

    The influence of long term treatment with choline alphoscerate on microanatomy of hippocampus and glial reaction was assessed in spontaneously hypertensive rats (SHR) used as an animal model of cerebrovascular disease. Choline alphoscerate is a cholinergic precursor, which has shown to be effective in countering cognitive symptoms in forms of dementia disorders of degenerative, vascular or combined origin. Male spontaneously hypertensive rats (SHR) aged 6 months and age-matched normotensive Wistar-Kyoto (WKY) rats were treated for 8 weeks with an oral daily dose of 100 mg/kg of choline alphoscerate, 285 mg/kg of phosphatidylcholine (lecithin) or vehicle. On the hippocampus of different animal groups, nerve cell number and GFAP-immunoreactive astrocytes were assessed by neuroanatomical, immunochemical and immunohistochemical techniques associated with quantitative analysis. Treatment with choline alphoscerate countered nerve cell loss and glial reaction primarily in the CA1 subfields and in the dentate gyrus of the hippocampus of SHR. Phosphatidylcholine did not affect hypertension-dependent changes in hippocampal microanatomy. Both compounds did not affect blood pressure values in SHR. These data suggest that choline alphoscerate may play a role in the countering hippocampal changes induced by cerebrovascular involvement. The observation that treatment with choline alphoscerate attenuates the extent of glial reaction in the hippocampus of SHR suggests also that the compound may afford neuroprotection in this animal model of vascular brain damage.

  10. Primary culture of glial cells from mouse sympathetic cervical ganglion: a valuable tool for studying glial cell biology.

    PubMed

    de Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2010-12-15

    Central nervous system glial cells as astrocytes and microglia have been investigated in vitro and many intracellular pathways have been clarified upon various stimuli. Peripheral glial cells, however, are not as deeply investigated in vitro despite its importance role in inflammatory and neurodegenerative diseases. Based on our previous experience of culturing neuronal cells, our objective was to standardize and morphologically characterize a primary culture of mouse superior cervical ganglion glial cells in order to obtain a useful tool to study peripheral glial cell biology. Superior cervical ganglia from neonatal C57BL6 mice were enzymatically and mechanically dissociated and cells were plated on diluted Matrigel coated wells in a final concentration of 10,000cells/well. Five to 8 days post plating, glial cell cultures were fixed for morphological and immunocytochemical characterization. Glial cells showed a flat and irregular shape, two or three long cytoplasm processes, and round, oval or long shaped nuclei, with regular outline. Cell proliferation and mitosis were detected both qualitative and quantitatively. Glial cells were able to maintain their phenotype in our culture model including immunoreactivity against glial cell marker GFAP. This is the first description of immunocytochemical characterization of mouse sympathetic cervical ganglion glial cells in primary culture. This work discusses the uses and limitations of our model as a tool to study many aspects of peripheral glial cell biology.

  11. Sex steroids inhibit osmotic swelling of retinal glial cells.

    PubMed

    Neumann, Florian; Wurm, Antje; Linnertz, Regina; Pannicke, Thomas; Iandiev, Ianors; Wiedemann, Peter; Reichenbach, Andreas; Bringmann, Andreas

    2010-04-01

    Osmotic swelling of glial cells may contribute to the development of retinal edema. We investigated whether sex steroids inhibit the swelling of glial somata in acutely isolated retinal slices and glial cells of the rat. Superfusion of retinal slices or cells from control animals with a hypoosmolar solution did not induce glial swelling, whereas glial swelling was observed in slices of postischemic and diabetic retinas. Progesterone, testosterone, estriol, and 17beta-estradiol prevented glial swelling with half-maximal effects at approximately 0.3, 0.6, 6, and 20 microM, respectively. The effect of progesterone was apparently mediated by transactivation of metabotropic glutamate receptors, P2Y1, and adenosine A1 receptors. The data suggest that sex steroids may inhibit cytotoxic edema in the retina.

  12. The use of glial data in human health assessments of environmental contaminants.

    PubMed

    Kraft, Andrew D

    2015-07-03

    Central nervous system (CNS) glia (i.e., astrocytes, microglia, and oligodendrocytes) are essential for maintaining neuronal homeostasis, and they orchestrate an organized cellular response to CNS injury. In addition to their beneficial roles, studies have demonstrated that disrupted glial function can have disastrous consequences on neuronal health. While effects on neuron-supportive glia are important to consider when evaluating neurotoxicity risk, interpreting glial changes is not always straightforward, particularly when attempting to discern pro-neurotoxic phenotypes from homeostatic processes or adaptive responses. To better understand how glia have been characterized and used in human health assessments of environmental contaminants (e.g., chemicals), an evaluation of all finalized assessments conducted by the U.S. Environmental Protection Agency's influential Integrated Risk Information System (IRIS) program between 1987 and 2013 was performed. Human health assessments to date have placed a clear emphasis on the neuronal cell response to potential toxicants, although more recent assessments increasingly include descriptions of glial changes. However, these descriptions are generally brief and non-specific, and they primarily consist of documenting gliosis following overt neuronal injury. As research interest in this topic continues to increase, methods for evaluating changes in glia continue to be expanded and refined, and assessors' confidence in the reliability of these data is likely to rise. Thus, glial data are anticipated to have an increasingly influential impact on the interpretation of neurotoxicity risk and underlying mechanisms. As our understanding of the complex roles these cells play grows, this knowledge is expected to support the inclusion of more extensive and specific descriptions of glial changes, including informed interpretations of the potential impact on CNS health, in future human health assessments.

  13. Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer; Levin, Edward D; Seidler, Frederic J

    2016-11-30

    The large number of compounds that needs to be tested for developmental neurotoxicity drives the need to establish in vitro models to evaluate specific neurotoxic endpoints. We used neural stem cells derived from rat neuroepithelium on embryonic day 14 to evaluate the impact of diverse toxicants on their ability to differentiate into glia and neurons: a glucocorticoid (dexamethasone), organophosphate insecticides (chlorpyrifos, diazinon, parathion), insecticides targeting the GABAA receptor (dieldrin, fipronil), heavy metals (Ni(2+), Ag(+)), nicotine and tobacco smoke extract. We found three broad groupings of effects. One diverse set of compounds, dexamethasone, the organophosphate pesticides, Ni(2+) and nicotine, suppressed expression of the glial phenotype while having little or no effect on the neuronal phenotype. The second pattern was restricted to the pesticides acting on GABAA receptors. These compounds promoted the glial phenotype and suppressed the neuronal phenotype. Notably, the actions of compounds eliciting either of these differentiation patterns were clearly unrelated to deficits in cell numbers: dexamethasone, dieldrin and fipronil all reduced cell numbers, whereas organophosphates and Ni(2+) had no effect. The third pattern, shared by Ag(+) and tobacco smoke extract, clearly delineated cytotoxicity, characterized by major cell loss with suppression of differentiation into both glial and neuronal phenotypes; but here again, there was some selectivity in that glia were suppressed more than neurons. Our results, from this survey with diverse compounds, point to convergence of neurotoxicant effects on a specific "decision node" that controls the emergence of neurons and glia from neural stem cells.

  14. 77 FR 37803 - Customer Clearing Documentation, Timing of Acceptance for Clearing, and Clearing Member Risk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-25

    ... Clearing, and Clearing Member Risk Management; Core Principles and Other Requirements for Designated... Clearing Member Risk Management, and Core Principles and Other Requirements for Designated Contract...

  15. APP-dependent glial cell line-derived neurotrophic factor gene expression drives neuromuscular junction formation.

    PubMed

    Stanga, Serena; Zanou, Nadège; Audouard, Emilie; Tasiaux, Bernadette; Contino, Sabrina; Vandermeulen, Gaëlle; René, Frédérique; Loeffler, Jean-Philippe; Clotman, Frédéric; Gailly, Philippe; Dewachter, Ilse; Octave, Jean-Noël; Kienlen-Campard, Pascal

    2016-05-01

    Besides its crucial role in the pathogenesis of Alzheimer's disease, the knowledge of amyloid precursor protein (APP) physiologic functions remains surprisingly scarce. Here, we show that APP regulates the transcription of the glial cell line-derived neurotrophic factor (GDNF). APP-dependent regulation of GDNF expression affects muscle strength, muscular trophy, and both neuronal and muscular differentiation fundamental for neuromuscular junction (NMJ) maturation in vivo In a nerve-muscle coculture model set up to modelize NMJ formation in vitro, silencing of muscular APP induces a 30% decrease in secreted GDNF levels and a 40% decrease in the total number of NMJs together with a significant reduction in the density of acetylcholine vesicles at the presynaptic site and in neuronal maturation. These defects are rescued by GDNF expression in muscle cells in the conditions where muscular APP has been previously silenced. Expression of GDNF in muscles of amyloid precursor protein null mice corrected the aberrant synaptic morphology of NMJs. Our findings highlight for the first time that APP-dependent GDNF expression drives the process of NMJ formation, providing new insights into the link between APP gene regulatory network and physiologic functions.-Stanga, S., Zanou, N., Audouard, E., Tasiaux, B., Contino, S., Vandermeulen, G., René, F., Loeffler, J.-P., Clotman, F., Gailly, P., Dewachter, I., Octave, J.-N., Kienlen-Campard, P. APP-dependent glial cell line-derived neurotrophic factor gene expression drives neuromuscular junction formation.

  16. Fine Surface Images That Reflect Cytoskeletal Structures in Cultured Glial Cells by Atomic Force Microscopy

    NASA Astrophysics Data System (ADS)

    Yamane, Yukako; Hatakeyama, Dai; Tojima, Takuro; Kawabata, Kazushige; Ushiki, Tatsuo; Ogura, Shigeaki; Abe, Kazuhiro; Ito, Etsuro

    1998-06-01

    The morphology of cultured glial cells was examined using a combination of atomic force microscopy (AFM) and immunofluorescence staining for cytoskeletons. The meshwork of type-1 astrocytes consisted of thick longitudinal and thin lateral lines on the cell surfaces observed by AFM; the former lines were confirmed to be reflections of actin filaments. The astrocytic processes of type-2 astrocytes were observed to be rugged on AFM. These structures were mainly affected by microtubules. Immunofluorescence imaging of microglia revealed that actin filaments and microtubules were arranged radially and wavily along the cell edge, respectively. AFM could detect these radial and wavy structures clearly. These results show that AFM can provide information on the cytoskeletons of glial cells, indicating that AFM is a useful tool for the morphological characterization of cells.

  17. Glial cells: Old cells with new twists

    PubMed Central

    Ndubaku, Ugo; de Bellard, Maria Elena

    2008-01-01

    Summary Based on their characteristics and function – migration, neural protection, proliferation, axonal guidance and trophic effects – glial cells may be regarded as probably the most versatile cells in our body. For many years, these cells were considered as simply support cells for neurons. Recently, it has been shown that they are more versatile than previously believed – as true stem cells in the nervous system – and are important players in neural function and development. There are several glial cell types in the nervous system: the two most abundant are oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Although both of these cells are responsible for myelination, their developmental origins are quite different. Oligodendrocytes originate from small niche populations from different regions of the central nervous system, while Schwann cells develop from a stem cell population (the neural crest) that gives rise to many cell derivatives besides glia and which is a highly migratory group of cells. PMID:18068219

  18. Long-term fate of neural precursor cells following transplantation into developing and adult CNS.

    PubMed

    Lepore, A C; Neuhuber, B; Connors, T M; Han, S S W; Liu, Y; Daniels, M P; Rao, M S; Fischer, I

    2006-05-12

    Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can

  19. Glial Na(+) -dependent ion transporters in pathophysiological conditions.

    PubMed

    Boscia, Francesca; Begum, Gulnaz; Pignataro, Giuseppe; Sirabella, Rossana; Cuomo, Ornella; Casamassa, Antonella; Sun, Dandan; Annunziato, Lucio

    2016-10-01

    Sodium dynamics are essential for regulating functional processes in glial cells. Indeed, glial Na(+) signaling influences and regulates important glial activities, and plays a role in neuron-glia interaction under physiological conditions or in response to injury of the central nervous system (CNS). Emerging studies indicate that Na(+) pumps and Na(+) -dependent ion transporters in astrocytes, microglia, and oligodendrocytes regulate Na(+) homeostasis and play a fundamental role in modulating glial activities in neurological diseases. In this review, we first briefly introduced the emerging roles of each glial cell type in the pathophysiology of cerebral ischemia, Alzheimer's disease, epilepsy, Parkinson's disease, Amyotrophic Lateral Sclerosis, and myelin diseases. Then, we discussed the current knowledge on the main roles played by the different glial Na(+) -dependent ion transporters, including Na(+) /K(+) ATPase, Na(+) /Ca(2+) exchangers, Na(+) /H(+) exchangers, Na(+) -K(+) -Cl(-) cotransporters, and Na(+) - HCO3- cotransporter in the pathophysiology of the diverse CNS diseases. We highlighted their contributions in cell survival, synaptic pathology, gliotransmission, pH homeostasis, and their role in glial activation, migration, gliosis, inflammation, and tissue repair processes. Therefore, this review summarizes the foundation work for targeting Na(+) -dependent ion transporters in glia as a novel strategy to control important glial activities associated with Na(+) dynamics in different neurological disorders. GLIA 2016;64:1677-1697.

  20. Glial heterotopia in an adult: A rare orbital mass

    PubMed Central

    Sundaresh, Divya Dabir; Mangala Gouri, S R

    2016-01-01

    Heterotopic glial tissue is very rare in the orbit. Our case was an adult, which is unique since most cases reported in literature involve children. We describe a case of a 60-year-old man who presented with an orbital mass, which histopathologically revealed heterotopic glial tissue. PMID:27958209

  1. Glial heterotopia of the lip: A rare presentation

    PubMed Central

    Dadaci, Mehmet; Bayram, Fazli Cengiz; Ince, Bilsev; Bilgen, Fatma

    2016-01-01

    Glial heterotopia represents collections of normal glial tissue in an abnormal location distant to the central nervous system or spinal canal with no intracranial connectivity. Nasal gliomas are non-neoplastic midline tumours, with limited growth potential and no similarity to the central nervous system gliomas. The nose and the nasopharynx are the most common sites of location. Existence of glial heterotopia in the lip region is a rare developmental disorder. We report a case of large glial heterotopia in the upper lip region in a full-term female newborn which had intracranial extension with a fibrotic band. After the surgery, there was no recurrence in the follow-up period of 3 years. When glial heterotopia, which is a rare midline anomaly, is suspected, possible intracranial connection and properties of the mass should be evaluated by magnetic resonance imaging. By this way, lower complication rate and better aesthetic results can be achieved with early diagnosis and proper surgery. PMID:27274134

  2. Neuron-Glial Interactions in Blood-Brain Barrier Formation

    PubMed Central

    Banerjee, Swati; Bhat, Manzoor A.

    2010-01-01

    The blood brain barrier (BBB) evolved to preserve the microenvironment of the highly excitable neuronal cells to allow for action potential generation and propagation. Intricate molecular interactions between two main cell types, the neurons and the glial cells, form the underlying basis of the critical functioning of the nervous system across species. In invertebrates, interactions between neurons and glial cells are central in establishing a functional BBB. However, in vertebrates, the BBB formation and function is coordinated by interactions between neurons, glial cells, and endothelial cells. Here we review the neuron-glial interaction–based blood barriers in invertebrates and vertebrates and provide an evolutionary perspective as to how a glial-barrier system in invertebrates evolved into an endothelial barrier system. We also summarize the clinical relevance of the BBB as this protective barrier becomes disadvantageous in the pharmacological treatment of various neurological disorders. PMID:17506642

  3. Photodynamic damage of glial cells in crayfish ventral nerve cord

    NASA Astrophysics Data System (ADS)

    Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

    2011-03-01

    Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

  4. Photodynamic damage of glial cells in crayfish ventral nerve cord

    NASA Astrophysics Data System (ADS)

    Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

    2010-10-01

    Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

  5. Glial influence on the Blood Brain Barrier

    PubMed Central

    Alvarez, Jorge Ivan; Katayama, Takahiro; Prat, Alexandre

    2013-01-01

    The Blood Brain Barrier (BBB) is a specialized vascular structure tightly regulating central nervous system (CNS) homeostasis. Endothelial cells are the central component of the BBB and control of their barrier phenotype resides on astrocytes and pericytes. Interactions between these cells and the endothelium promote and maintain many of the physiological and metabolic characteristics that are unique to the BBB. In this review we describe recent findings related to the involvement of astroglial cells, including radial glial cells, in the induction of barrier properties during embryogenesis and adulthood. In addition, we describe changes that occur in astrocytes and endothelial cells during injury and inflammation with a particular emphasis on alterations of the BBB phenotype. GLIA 2013;61:1939–1958 PMID:24123158

  6. Glial Biology in Learning and Cognition

    PubMed Central

    Araque, Alfonso; Johansen-Berg, Heidi; Lim, Soo-Siang; Lynch, Gary; Nave, Klaus-Armin; Nedergaard, Maiken; Perez, Ray; Sejnowski, Terrence; Wake, Hiroaki

    2014-01-01

    Neurons are exquisitely specialized for rapid electrical transmission of signals, but some properties of glial cells, which do not communicate with electrical impulses, are well suited for participating in complex cognitive functions requiring broad spatial integration and long-term temporal regulation. Astrocytes, microglia, and oligodendrocytes all have biological properties that could influence learning and cognition. Myelination by oligodendrocytes increases conduction velocity, affecting spike timing and oscillations in neuronal activity. Astrocytes can modulate synaptic transmission and may couple multiple neurons and synapses into functional assemblies. Microglia can remove synapses in an activity-dependent manner altering neural networks. Incorporating glia into a bicellular mechanism of nervous system function may help answer long-standing questions concerning the cellular mechanisms of learning and cognition. PMID:24122821

  7. Culturing conditions determine neuronal and glial excitability.

    PubMed

    Stoppelkamp, Sandra; Riedel, Gernot; Platt, Bettina

    2010-12-15

    The cultivation of pure neuronal cultures is considered advantageous for the investigation of cell-type specific responses (such as transmitter release and also pharmacological agents), however, divergent results are a likely consequence of media modifications and culture composition. Using Fura-2 based imaging techniques, we here set out to compare calcium responses of rat hippocampal neurones and glia to excitatory stimulation with l-glutamate in different culture types and media. Neurones in neurone-enriched cultures had increased responses to 10 μM and 100 μM l-glutamate (+43 and 45%, respectively; p's< 0.001) and a slower recovery compared to mixed cultures, indicating heightened excitability. In matured (15-20 days in vitro) mixed cultures, neuronal responder rates were suppressed in a neurone-supportive medium (Neurobasal-A, NB: 65%) compared to a general-purpose medium (supplemented minimal essential medium, MEM: 96%). Glial response size in contrast did not differ greatly in isolated or mixed cultures maintained in MEM, but responder rates were suppressed in both culture types in NB (e.g. 10 μM l-glutamate responders in mixed cultures: 29% in NB, 71% in MEM). This indicates that medium composition is more important for glial excitability than the presence of neurones, whereas the presence of glia has an important impact on neuronal excitability. Therefore, careful consideration of culturing conditions is crucial for interpretation and comparison of experimental results. Especially for investigations of toxicity and neuroprotection mixed cultures may be more physiologically relevant over isolated cultures as they comprise aspects of mutual influences between glia and neurones.

  8. [Death of neurons and glial cells, induced by a photodynamic injury: signaling processes and neurone-glial interactions].

    PubMed

    Uzdenskiĭ, A B; Kolosov, M S; Lobanov, A V

    2007-01-01

    The mechanisms of photodynamic (PD) injury of neurons and glial cells are reviewed. Neuron responses: firing stimulation at high photosensitizer concentrations and inhibition at low concentrations (< 10(-7) M) that were followed by necrosis, are described. Glial cells died from both necrosis and apoptosis. Local laser inactivation of a neuron enhanced PD-induced apoptosis of glial cells, thus indicating that neuron maintained the survival of glia. Inter- and intracellular signaling mediated photodamage of these cells. Using inhibitors or activators of signaling proteins, the involvement of Ca(2+)-, adenylate cyclase- and tyrosine kinase-mediated signaling pathways in responses of neurons and glial cells to photosensitization was shown. Their pharmacological modulation can change selectivity of PD injury of neuronal and glial cells and efficiency of PD therapy.

  9. Doublecortin in Oligodendrocyte Precursor Cells in the Adult Mouse Brain

    PubMed Central

    Boulanger, Jenna J.; Messier, Claude

    2017-01-01

    Key Points Oligodendrocyte precursor cells express doublecortin, a microtubule-associated protein.Oligodendrocyte precursor cells express doublecortin, but at a lower level of expression than in neuronal precursor.Doublecortin is not associated with a potential immature neuronal phenotype in Oligodendrocyte precursor cells. Oligodendrocyte precursor cells (OPC) are glial cells that differentiate into myelinating oligodendrocytes during embryogenesis and early stages of post-natal life. OPCs continue to divide throughout adulthood and some eventually differentiate into oligodendrocytes in response to demyelinating lesions. There is growing evidence that OPCs are also involved in activity-driven de novo myelination of previously unmyelinated axons and myelin remodeling in adulthood. Considering these roles in the adult brain, OPCs are likely mobile cells that can migrate on some distances before they differentiate into myelinating oligodendrocytes. A number of studies have noted that OPCs express doublecortin (DCX), a microtubule-associated protein expressed in neural precursor cells and in migrating immature neurons. Here we describe the distribution of DCX in OPCs. We found that almost all OPCs express DCX, but the level of expression appears to be much lower than what is found in neural precursor. We found that DCX is downregulated when OPCs start expressing mature oligodendrocyte markers and is absent in myelinating oligodendrocytes. DCX does not appear to signal an immature neuronal phenotype in OPCs in the adult mouse brain. Rather, it could be involved either in cell migration, or as a marker of an immature oligodendroglial cell phenotype.

  10. How Does Transcranial Magnetic Stimulation Influence Glial Cells in the Central Nervous System?

    PubMed Central

    Cullen, Carlie L.; Young, Kaylene M.

    2016-01-01

    Transcranial magnetic stimulation (TMS) is widely used in the clinic, and while it has a direct effect on neuronal excitability, the beneficial effects experienced by patients are likely to include the indirect activation of other cell types. Research conducted over the past two decades has made it increasingly clear that a population of non-neuronal cells, collectively known as glia, respond to and facilitate neuronal signaling. Each glial cell type has the ability to respond to electrical activity directly or indirectly, making them likely cellular effectors of TMS. TMS has been shown to enhance adult neural stem and progenitor cell (NSPC) proliferation, but the effect on cell survival and differentiation is less certain. Furthermore there is limited information regarding the response of astrocytes and microglia to TMS, and a complete paucity of data relating to the response of oligodendrocyte-lineage cells to this treatment. However, due to the critical and yet multifaceted role of glial cells in the central nervous system (CNS), the influence that TMS has on glial cells is certainly an area that warrants careful examination. PMID:27092058

  11. Impaired glial buffering hampers antidromic conduction of CA1 neurons during hypoxia.

    PubMed

    Park, Youn-Kwan; Kim, Seok-Joon

    2009-07-14

    Increased potassium conductance during hypoxia causes membrane hyperpolarization and a resultant increase in extracellular potassium concentration ([K(+)](o)). In addition, glial buffering of [K(+)](o) is the key mechanism for clearing excess K(+) and is important for neuronal function and survival. Here, we studied the effect of glial buffering of [K(+)](o) on neural impulse conduction during hypoxia using a potassium-selective electrode and evoked potential recording in rat hippocampal slices. The increase in [K(+)](o) during hypoxia was modest and there were no significant differences between the layers. The [K(+)](o) during hypoxia was significantly elevated by addition of barium (1 mM), especially in the stratum pyramidale and stratum oriens. Although synaptic transmission was depressed during hypoxia, the presynaptic volley and antidromic population spike mostly remained unchanged. With the addition of barium, antidromic conduction was more profoundly affected than the presynaptic volley. When presynaptic inhibition was precluded by including a selective A1 adenosine receptor blocker to restore synaptic transmission, blockade of the antidromic conduction became more evident compared with the blockade of other recorded field potentials. These findings are compatible with regional differences in the increase of [K(+)](o) and suggest that glial buffering of high [K(+)](o) is important in antidromic conduction during hypoxia.

  12. Neuronal and glial purinergic receptors functions in neuron development and brain disease

    PubMed Central

    del Puerto, Ana; Wandosell, Francisco; Garrido, Juan José

    2013-01-01

    Brain development requires the interaction of complex signaling pathways, involving different cell types and molecules. For a long time, most attention has focused on neurons in a neuronocentric conceptualization of central nervous system development, these cells fulfilling an intrinsic program that establishes the brain’s morphology and function. By contrast, glia have mainly been studied as support cells, offering guidance or as the cells that react to brain injury. However, new evidence is appearing that demonstrates a more fundamental role of glial cells in the control of different aspects of neuronal development and function, events in which the influence of neurons is at best weak. Moreover, it is becoming clear that the function and organization of the nervous system depends heavily on reciprocal neuron–glia interactions. During development, neurons are often generated far from their final destination and while intrinsic mechanisms are responsible for neuronal migration and growth, they need support and regulatory influences from glial cells in order to migrate correctly. Similarly, the axons emitted by neurons often have to reach faraway targets and in this sense, glia help define the way that axons grow. Moreover, oligodendrocytes and Schwann cells ultimately envelop axons, contributing to the generation of nodes of Ranvier. Finally, recent publications show that astrocytes contribute to the modulation of synaptic transmission. In this sense, purinergic receptors are expressed widely by glial cells and neurons, and recent evidence points to multiple roles of purines and purinergic receptors in neuronal development and function, from neurogenesis to axon growth and functional axonal maturation, as well as in pathological conditions in the brain. This review will focus on the role of glial and neuronal secreted purines, and on the purinergic receptors, fundamentally in the control of neuronal development and function, as well as in diseases of the

  13. ErbB2 activation contributes to de-differentiation of astrocytes into radial glial cells following induction of scratch-insulted astrocyte conditioned medium.

    PubMed

    Yang, Hao; Ling, Weng; Vitale, Angela; Olivera, Cathy; Min, Yan; You, Siwei

    2011-12-01

    Radial glial cells play a significant role in the repair of spinal cord injuries as they exert critical role in the neurogenesis and act as a scaffold for neuronal migration. Our previous study showed that mature astrocytes of spinal cord can undergo a de-differentiation process and further transform into pluripotential neural precursors; the occurrence of these complex events arise directly from the induction of diffusible factors released from scratch-insulted astrocytes. However, it is unclear whether astrocytes can also undergo rejuvenation to revert to a radial glial progenitor phenotype after the induction of scratch-insulted astrocytes conditioned medium (ACM). Furthermore, the mechanism of astrocyte de-differentiation to the progenitor cells is still unclear. Here we demonstrate that upon treating mature astrocytes with ACM for 10 days, the astrocytes exhibit progressive morphological and functional conversion to radial glial cells. These changes include the appearance of radial glial progenitor cells, changes in the immunophenotypical profiles, characterized by the co-expression of nestin, paired homeobox protein (Pax6) and RC2 as well as enhanced capability of multipotential differentiation. Concomitantly, ErbB2 protein level was progressively up-regulated. Thereby these results provide a potential mechanism by which ACM could induce mature astrocytes to regain the profile of radial glial progenitors due to activating the ErbB2 signaling pathways.

  14. Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction.

    PubMed

    Hoegg-Beiler, Maja B; Sirisi, Sònia; Orozco, Ian J; Ferrer, Isidre; Hohensee, Svea; Auberson, Muriel; Gödde, Kathrin; Vilches, Clara; de Heredia, Miguel López; Nunes, Virginia; Estévez, Raúl; Jentsch, Thomas J

    2014-03-19

    Defects in the astrocytic membrane protein MLC1, the adhesion molecule GlialCAM or the chloride channel ClC-2 underlie human leukoencephalopathies. Whereas GlialCAM binds ClC-2 and MLC1, and modifies ClC-2 currents in vitro, no functional connections between MLC1 and ClC-2 are known. Here we investigate this by generating loss-of-function Glialcam and Mlc1 mouse models manifesting myelin vacuolization. We find that ClC-2 is unnecessary for MLC1 and GlialCAM localization in brain, whereas GlialCAM is important for targeting MLC1 and ClC-2 to specialized glial domains in vivo and for modifying ClC-2's biophysical properties specifically in oligodendrocytes (OLs), the cells chiefly affected by vacuolization. Unexpectedly, MLC1 is crucial for proper localization of GlialCAM and ClC-2, and for changing ClC-2 currents. Our data unmask an unforeseen functional relationship between MLC1 and ClC-2 in vivo, which is probably mediated by GlialCAM, and suggest that ClC-2 participates in the pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts.

  15. Synthetic carbon precursor materials

    SciTech Connect

    Frame, B.J.

    1986-03-01

    Synthetic carbon precursor systems offer advantages over natural petroleum and coal-tar pitch precursors in that they can reproducibly provide a material with a known and uniform composition. They also permit controlled modifications of the derived carbon's properties through variations in the precursor's properties and processing conditions. Extensive research efforts at Oak Ridge have been directed toward the production and characterization of synthetic carbon precursors and the correlations that exist between carbon precursor properties and the properties of the ultimate carbon. This report describes how synthetic carbon precursors can be used to tailor and develop reproducible carbon structures for advanced materials applications. The potential and capability for performing carbon material development at Oak Ridge is also described.

  16. Globular glial tauopathies (GGT): consensus recommendations.

    PubMed

    Ahmed, Zeshan; Bigio, Eileen H; Budka, Herbert; Dickson, Dennis W; Ferrer, Isidro; Ghetti, Bernardino; Giaccone, Giorgio; Hatanpaa, Kimmo J; Holton, Janice L; Josephs, Keith A; Powers, James; Spina, Salvatore; Takahashi, Hitoshi; White, Charles L; Revesz, Tamas; Kovacs, Gabor G

    2013-10-01

    Recent studies have highlighted a group of 4-repeat (4R) tauopathies that are characterised neuropathologically by widespread, globular glial inclusions (GGIs). Tau immunohistochemistry reveals 4R immunoreactive globular oligodendroglial and astrocytic inclusions and the latter are predominantly negative for Gallyas silver staining. These cases are associated with a range of clinical presentations, which correlate with the severity and distribution of underlying tau pathology and neurodegeneration. Their heterogeneous clinicopathological features combined with their rarity and under-recognition have led to cases characterised by GGIs being described in the literature using various and redundant terminologies. In this report, a group of neuropathologists form a consensus on the terminology and classification of cases with GGIs. After studying microscopic images from previously reported cases with suspected GGIs (n = 22), this panel of neuropathologists with extensive experience in the diagnosis of neurodegenerative diseases and a documented record of previous experience with at least one case with GGIs, agreed that (1) GGIs were present in all the cases reviewed; (2) the morphology of globular astrocytic inclusions was different to tufted astrocytes and finally that (3) the cases represented a number of different neuropathological subtypes. They also agreed that the different morphological subtypes are likely to be part of a spectrum of a distinct disease entity, for which they recommend that the overarching term globular glial tauopathy (GGT) should be used. Type I cases typically present with frontotemporal dementia, which correlates with the fronto-temporal distribution of pathology. Type II cases are characterised by pyramidal features reflecting motor cortex involvement and corticospinal tract degeneration. Type III cases can present with a combination of frontotemporal dementia and motor neuron disease with fronto-temporal cortex, motor cortex and

  17. Globular glial tauopathies (GGT): consensus recommendations

    PubMed Central

    Bigio, Eileen H.; Budka, Herbert; Dickson, Dennis W.; Ferrer, Isidro; Ghetti, Bernardino; Giaccone, Giorgio; Hatanpaa, Kimmo J.; Holton, Janice L.; Josephs, Keith A.; Powers, James; Spina, Salvatore; Takahashi, Hitoshi; White, Charles L.; Revesz, Tamas

    2014-01-01

    Rrecent studies have highlighted a group of 4-repeat (4R) tauopathies that are characterised neuropathologically by widespread, globular glial inclusions (GGIs). Tau immunohistochemistry reveals 4R immunore-active globular oligodendroglial and astrocytic inclusions and the latter are predominantly negative for Gallyas silver staining. These cases are associated with a range of clinical presentations, which correlate with the severity and distribution of underlying tau pathology and neurodegeneration. Their heterogeneous clinicopathological features combined with their rarity and under-recognition have led to cases characterised by GGIs being described in the literature using various and redundant terminologies. In this report, a group of neuropathologists form a consensus on the terminology and classification of cases with GGIs. After studying microscopic images from previously reported cases with suspected GGIs (n = 22), this panel of neuropathologists with extensive experience in the diagnosis of neurodegenerative diseases and a documented record of previous experience with at least one case with GGIs, agreed that (1) GGIs were present in all the cases reviewed; (2) the morphology of globular astrocytic inclusions was different to tufted astrocytes and finally that (3) the cases represented a number of different neuropathological subtypes. They also agreed that the different morphological subtypes are likely to be part of a spectrum of a distinct disease entity, for which they recommend that the overarching term globular glial tauopathy (GGT) should be used. Type I cases typically present with frontotemporal dementia, which correlates with the fronto-temporal distribution of pathology. Type II cases are characterised by pyramidal features reflecting motor cortex involvement and corticospinal tract degeneration. Type III cases can present with a combination of frontotemporal dementia and motor neuron disease with fronto-temporal cortex, motor cortex and

  18. Serum albumin induces osmotic swelling of rat retinal glial cells.

    PubMed

    Löffler, Silvana; Wurm, Antje; Kutzera, Franziska; Pannicke, Thomas; Krügel, Katja; Linnertz, Regina; Wiedemann, Peter; Reichenbach, Andreas; Bringmann, Andreas

    2010-03-04

    Edema in the ischemic neural tissue develops by increased vascular permeability associated with extravasation of albumin, and by glial swelling. Here, we show that bovine serum albumin acutely administered to slices of the rat retina causes swelling of glial somata under hypoosmotic conditions. The effect of albumin was dose-dependent, with half-maximal and maximal effects at 10 nM and 1 microM, respectively, and was mediated by activation of transforming growth factor-beta receptor type II, oxidative stress, and the production of arachidonic acid and prostaglandins. Albumin-induced glial swelling was prevented by glutamate and purinergic receptor agonists. The data suggest that serum albumin may induce glial swelling in the presence of osmotic gradients.

  19. Nitric oxide mediates glial-induced neurodegeneration in Alexander disease.

    PubMed

    Wang, Liqun; Hagemann, Tracy L; Kalwa, Hermann; Michel, Thomas; Messing, Albee; Feany, Mel B

    2015-11-26

    Glia play critical roles in maintaining the structure and function of the nervous system; however, the specific contribution that astroglia make to neurodegeneration in human disease states remains largely undefined. Here we use Alexander disease, a serious degenerative neurological disorder caused by astrocyte dysfunction, to identify glial-derived NO as a signalling molecule triggering astrocyte-mediated neuronal degeneration. We further find that NO acts through cGMP signalling in neurons to promote cell death. Glial cells themselves also degenerate, via the DNA damage response and p53. Our findings thus define a specific mechanism for glial-induced non-cell autonomous neuronal cell death, and identify a potential therapeutic target for reducing cellular toxicity in Alexander disease, and possibly other neurodegenerative disorders with glial dysfunction.

  20. Complex and differential glial responses in Alzheimer's disease and ageing.

    PubMed

    Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

    2016-01-01

    Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

  1. Glial cell biology in the Great Lakes region.

    PubMed

    Feinstein, Douglas L; Skoff, Robert P

    2016-03-31

    We report on the tenth bi-annual Great Lakes Glial meeting, held in Traverse City, Michigan, USA, September 27-29 2015. The GLG meeting is a small conference that focuses on current research in glial cell biology. The array of functions that glial cells (astrocytes, microglia, oligodendrocytes, Schwann cells) play in health and disease is constantly increasing. Despite this diversity, GLG meetings bring together scientists with common interests, leading to a better understanding of these cells. This year's meeting included two keynote speakers who presented talks on the regulation of CNS myelination and the consequences of stress on Schwann cell biology. Twenty-two other talks were presented along with two poster sessions. Sessions covered recent findings in the areas of microglial and astrocyte activation; age-dependent changes to glial cells, Schwann cell development and pathology, and the role of stem cells in glioma and neural regeneration.

  2. Glial cells in (patho)physiology

    PubMed Central

    Parpura, Vladimir; Heneka, Michael T.; Montana, Vedrana; Oliet, Stéphane H.R.; Schousboe, Arne; Haydon, Philip. G.; Stout, Randy F.; Spray, David C.; Reichenbach, Andreas; Pannicke, Thomas; Pekny, Milos; Pekna, Marcela; Zorec, Robert; Verkhratsky, Alexei

    2012-01-01

    Neuroglial cells define brain homeostasis and mount defense against pathological insults. Astroglia regulate neurogenesis and development of brain circuits. In the adult brain, astrocytes enter into intimate dynamic relationship with neurons, especially at synaptic sites where they functionally form the tripartite synapse. At these sites astrocytes regulate ion and neurotransmitter homeostasis, metabolically support neurons and monitor synaptic activity; one of the readouts of the latter manifests in astrocytic intracellular Ca2+ signals. This form of astrocytic excitability can lead to release of chemical transmitters via Ca2+-dependent exocytosis. Once in the extracellular space, gliotransmitters can modulate synaptic plasticity and cause changes in behavior. Besides these physiological tasks, astrocytes are fundamental for progression and outcome of neurological diseases. In Alzheimer’s disease, for example, astrocytes may contribute to the etiology of this disorder. Highly lethal glial-derived tumors use signaling trickery to coerce normal brain cells to assist tumor invasiveness. This review sheds new light on the brain operation in health and disease, but also points to many unknowns. PMID:22251135

  3. Corticobasal syndrome with novel argyrophilic glial inclusions.

    PubMed

    Rippon, Gregory A; Staugaitis, S M; Chin, Steven S M; Goldman, James E; Marder, K

    2005-05-01

    A 42-year-old, left-handed woman first noted impaired dexterity of the dominant hand, soon followed by dysarthria and cognitive decline. Over a 4-year period, she developed severe left-sided apraxia with eventual neglect of the left arm and progressive extrapyramidal signs. Cognitive testing showed progressive executive, visuospatial, fluency, and naming impairment with relative preservation of memory. Single-photon emission computed tomography demonstrated asymmetric right posterior frontal and superior parietal hypoperfusion. The clinical impression was corticobasal degeneration. At autopsy, severe atrophy was seen in the perirolandic and frontal regions. There was marked neuronal loss and gliosis in the posterior frontal and precentral regions and less severe pathology in prefrontal, temporal, and parietal areas. Mild to moderate gliosis and neuronal loss were also seen in the putamen, globus pallidus, subthalamic, and dentate nuclei. Gallyas silver stain revealed numerous inclusions adjacent to oligodendrocyte nuclei in white and gray matter of affected cortical and subcortical regions. The gracile inclusions were wavy, slender, and stained positively with antibodies to ubiquitin and alphaB-crystallin but not to microtubule-associated proteins (tau, MAP1B, MAP2), tubulin, neurofilaments, glial fibrillary acidic protein, or alpha-synuclein. The argyrophilic inclusions identified in this case are distinct from those previously described in neurodegenerative diseases.

  4. Glial hemichannels and their involvement in aging and neurodegenerative diseases.

    PubMed

    Orellana, Juan A; von Bernhardi, Rommy; Giaume, Christian; Sáez, Juan C

    2012-01-26

    During the last two decades, it became increasingly evident that glial cells accomplish a more important role in brain function than previously thought. Glial cells express pannexins and connexins, which are member subunits of two protein families that form membrane channels termed hemichannels. These channels communicate intra- and extracellular compartments and allow the release of autocrine/paracrine signaling molecules [e.g., adenosine triphosphate (ATP), glutamate, nicotinamide adenine dinucleotide, and prostaglandin E2] to the extracellular milieu, as well as the uptake of small molecules (e.g., glucose). An increasing body of evidence has situated glial hemichannels as potential regulators of the beginning and maintenance of homeostatic imbalances observed in diverse brain diseases. Here, we review and discuss the current evidence about the possible role of glial hemichannels on neurodegenerative diseases. A subthreshold pathological threatening condition leads to microglial activation, which keeps active defense and restores the normal function of the central nervous system. However, if the stimulus is deleterious, microglial cells and the endothelium become overactivated, both releasing bioactive molecules (e.g., glutamate, cytokines, prostaglandins, and ATP), which increase the activity of glial hemichannels, reducing the astroglial neuroprotective functions, and further reducing neuronal viability. Because ATP and glutamate are released via glial hemichannels in neurodegenerative conditions, it is expected that they contribute to neurotoxicity. More importantly, toxic molecules released via glial hemichannels could increase the Ca2+ entry in neurons also via neuronal hemichannels, leading to neuronal death. Therefore, blockade of hemichannels expressed by glial cells and/or neurons during neuroinflammation might prevent neurodegeneration.

  5. Delayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity

    PubMed Central

    Purice, Maria D.; Speese, Sean D.; Logan, Mary A.

    2016-01-01

    Advanced age is the greatest risk factor for neurodegenerative disorders, but the mechanisms that render the senescent brain vulnerable to disease are unclear. Glial immune responses provide neuroprotection in a variety of contexts. Thus, we explored how glial responses to neurodegeneration are altered with age. Here we show that glia–axon phagocytic interactions change dramatically in the aged Drosophila brain. Aged glia clear degenerating axons slowly due to low phosphoinositide-3-kinase (PI3K) signalling and, subsequently, reduced expression of the conserved phagocytic receptor Draper/MEGF10. Importantly, boosting PI3K/Draper activity in aged glia significantly reverses slow phagocytic responses. Moreover, several hours post axotomy, early hallmarks of Wallerian degeneration (WD) are delayed in aged flies. We propose that slow clearance of degenerating axons is mechanistically twofold, resulting from deferred initiation of axonal WD and reduced PI3K/Draper-dependent glial phagocytic function. Interventions that boost glial engulfment activity, however, can substantially reverse delayed clearance of damaged neuronal debris. PMID:27647497

  6. Phenotype overlap in glial cell populations: astroglia, oligodendroglia and NG-2(+) cells

    PubMed Central

    Alghamdi, Badrah; Fern, Robert

    2015-01-01

    The extent to which NG-2(+) cells form a distinct population separate from astrocytes is central to understanding whether this important cell class is wholly an oligodendrocyte precursor cell (OPC) or has additional functions akin to those classically ascribed to astrocytes. Early immuno-staining studies indicate that NG-2(+) cells do not express the astrocyte marker GFAP, but orthogonal reconstructions of double-labeled confocal image stacks here reveal a significant degree of co-expression in individual cells within post-natal day 10 (P10) and adult rat optic nerve (RON) and rat cortex. Extensive scanning of various antibody/fixation/embedding approaches identified a protocol for selective post-embedded immuno-gold labeling. This first ultrastructural characterization of identified NG-2(+) cells revealed populations of both OPCs and astrocytes in P10 RON. NG-2(+) astrocytes had classic features including the presence of glial filaments but low levels of glial filament expression were also found in OPCs and myelinating oligodendrocytes. P0 RONs contained few OPCs but positively identified astrocytes were observed to ensheath pre-myelinated axons in a fashion previously described as a definitive marker of the oligodendrocyte lineage. Astrocyte ensheathment was also apparent in P10 RONs, was absent from developing nodes of Ranvier and was never associated with compact myelin. Astrocyte processes were also shown to encapsulate some oligodendrocyte somata. The data indicate that common criteria for delineating astrocytes and oligodendroglia are insufficiently robust and that astrocyte features ascribed to OPCs may arise from misidentification. PMID:26106302

  7. Asymptomatic and symptomatic glial cysts of the pineal gland.

    PubMed

    Taraszewska, Anna; Matyja, Ewa; Koszewski, Waldemar; Zaczyński, Artur; Bardadin, Krzysztof; Czernicki, Zbigniew

    2008-01-01

    Glial cysts of the pineal gland are benign and mostly asymptomatic incidental lesions found in the brain MRI or at autopsy examinations. In rare cases pineal cysts become symptomatic and require surgical intervention. Symptomatic glial cysts may be clinically and radiologically indistinguishable from cystic neoplasms of the pineal region; therefore, histopathological diagnosis is critical for further prognosis and therapy in operated patients. In this paper we present detailed histopathological characteristics of symptomatic glial cysts in 2 surgical cases and of asymptomatic cysts of the pineal gland found at random in 3 autopsy cases. Both surgical patients, a 19-year-old girl and a 17-year-old boy, presented with severe headaches, associated with syncope in one case and insomnia in the second one. Preoperative MR imaging suggested tumour of the pineal gland in case no. 2. Histopathological and immunohistochemical examination of the specimens from both surgical and all autopsy cases revealed a characteristic pattern of cystic structures within the pineal gland, surrounded by layers of a dense fibrillar glial tissue and pineal parenchyma, consistent with non-neoplastic glial cysts. Although histopathological findings in asymptomatic and symptomatic cysts are essentially the same, the cyst in surgical case 1 was unilocular and partly lined with ependymal cells, whereas the cysts in other cases were multilocular, comprising cavities of various size, formed in the central part of gliotic tissue or directly within the pineal parenchyma, and lacked ependymal lining. Possible pathophysiological and clinicopathological significance of some morphological variants of pineal glial cysts is discussed.

  8. Clear Thinking about Alternative Therapies

    MedlinePlus

    ... industry, with corporations both large and small vigorously marketing their products. 5 | Clear Thinking about Alternative Therapies ... Once the FDA has cleared the product for marketing, people are protected by disclosure requirements such as ...

  9. Polyimide Precursor Solid Residuum

    NASA Technical Reports Server (NTRS)

    Weiser, Erik S. (Inventor); St.Clair, Terry L. (Inventor); Echigo, Yoshiaki (Inventor); Kaneshiro, Hisayasu (Inventor)

    2001-01-01

    A polyimide precursor solid residuum is an admixture of an aromatic dianhydride or derivative thereof and an aromatic diamine or derivative thereof plus a complexing agent, which is complexed with the admixture by hydrogen bonding. The polyimide precursor solid residuum is effectively employed in the preparation of polyimide foam and the fabrication of polyimide foam structures.

  10. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins

    PubMed Central

    Lisak, Robert P; Benjamins, Joyce A; Bealmear, Beverly; Nedelkoska, Liljana; Yao, Bin; Land, Susan; Studzinski, Diane

    2007-01-01

    Background In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells. Methods To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the effects of cytokines typical of Th1 and Th2 lymphocytes and monocyte/macrophages (M/M) on CNS glia after 6 hours of treatment. Results In this paper we focus on changes with potential relevance for neuroprotection and axon/glial interactions. Each mixture of cytokines induced a unique pattern of changes in genes for neurotrophins, growth and maturation factors and related receptors; most notably an alternatively spliced form of trkC was markedly downregulated by Th1 and M/M cytokines, while Th2 cytokines upregulated BDNF. Genes for molecules of potential importance in axon/glial interactions, including cell adhesion molecules, connexins, and some molecules traditionally associated with neurons showed significant changes, while no genes for myelin-associated genes were regulated at this early time point. Unexpectedly, changes occurred in several genes for proteins initially associated with retina, cancer or bone development, and not previously reported in glial cells. Conclusion Each of the three cytokine mixtures induced specific changes in gene expression that could be altered by pharmacologic strategies to promote protection of the central nervous system. PMID:18088439

  11. Optical clearing of articular cartilage: a comparison of clearing agents

    NASA Astrophysics Data System (ADS)

    Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

    2015-07-01

    Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

  12. Oligodendrocyte precursor cells generate pituicytes in vivo during neurohypophysis development.

    PubMed

    Virard, Isabelle; Coquillat, Delphine; Bancila, Mircea; Kaing, Sovann; Durbec, Pascale

    2006-02-01

    In the vertebrate brain, much remains to be understood concerning the origin of glial cell diversity and the potential lineage relationships between the various types of glia. Besides astrocytes and myelin-forming oligodendrocytes, other macroglial cell populations are found in discrete areas of the central nervous system (CNS). They share functional features with astrocytes and oligodendrocytes but also display specific characteristics. Such specialized cells, called pituicytes, are located in the neurohypophysis (NH). Our work focuses on the lineage of the pituicytes during rodent development. First, we show that cells identified with a combination of oligodendrocyte precursor cell (OPC) markers are present in the developing rat NH. In culture, neonatal NH progenitors also share major functional characteristics with OPCs, being both migratory and bipotential, i.e. able to give rise to type 2 astrocytes and oligodendrocytes. We then observe that, either in vitro or after transplantation into myelin-deficient Shiverer brain, pieces of NH generate myelinating oligodendrocytes, confirming the oligodendrogenic potentiality of NH cells. However, no mature oligodendrocyte can be found in the NH. This led us to hypothesize that the OPCs present in the developing NH might be generating other glial cells, especially the pituicytes. Consistent with this hypothesis, the OPCs appear during NH development before pituicytes differentiate. Finally, we establish a lineage relationship between olig1+ cells, most likely OPCs, and the pituicytes by fate-mapping experiments using genetically engineered mice. This constitutes the first demonstration that OPCs generate glial cells other than oligodendrocytes in vivo.

  13. Precursors to Lymphoproliferative Malignancies

    PubMed Central

    Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

    2013-01-01

    We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. PMID:23549397

  14. Differential properties of dentate gyrus and CA1 neural precursors.

    PubMed

    Becq, H; Jorquera, I; Ben-Ari, Y; Weiss, S; Represa, A

    2005-02-05

    In the present article we investigated the properties of CA1 and dentate gyrus cell precursors in adult rodents both in vivo and in vitro. Cell proliferation in situ was investigated by rating the number of cells incorporating BrdU after kainate-induced seizures. CA1 precursors displayed a greater proliferation capacity than dentate gyrus precursors. The majority of BrdU-labeled cells in CA1 expressed Nestin and Mash-1, two markers of neural precursors. BrdU-positive cells in the dentate gyrus expressed Nestin, but only a few expressed Mash-1. In animals pretreated with the antimitotic azacytidine, the capacity of kainate to enhance the proliferation was higher in CA1 than in the dentate gyrus. Differences in intrinsic progenitor cell activity could underlie these different expansion capacities. Thus, we compared the renewal- expansion and multipotency of dentate gyrus and CA1 precursors isolated in vitro. We found that the dissected CA1 region, including the periventricular zone, is enriched in neurosphere-forming cells (presumed stem cells), which respond to either EGF or FGF-2. Dentate gyrus contains fewer neurosphere-forming cells and none that respond to FGF-2 alone. Neurospheres generated from CA1 were multipotent and produced neurons, astrocytes, and oligodendrocytes, while dentate gyrus neurospheres mostly produced glial cells. The analysis of the effects of EGF on organotypic cultures of hippocampal slices depicted similar features: BrdU and Nestin immunoreactivities increased after EGF treatment in CA1 but not in the dentate gyrus. These results suggest that CA1 precursors are more stem-cell-like than granule cell precursors, which may represent a more restricted precursor cell.

  15. Earthquakes: hydrogeochemical precursors

    USGS Publications Warehouse

    Ingebritsen, Steven E.; Manga, Michael

    2014-01-01

    Earthquake prediction is a long-sought goal. Changes in groundwater chemistry before earthquakes in Iceland highlight a potential hydrogeochemical precursor, but such signals must be evaluated in the context of long-term, multiparametric data sets.

  16. Modification of glial response in hibernation: a patch-clamp study on glial cells acutely isolated from hibernating land snail.

    PubMed

    Nikolic, Ljiljana; Bataveljic, Danijela; Andjus, Pavle R; Moldovan, Ivana; Nedeljkovic, Miodrag; Petkovic, Branka

    2014-12-01

    Hibernation is a dormant state of some animal species that enables them to survive harsh environmental conditions during the winter seasons. In the hibernating state, preservation of neuronal rhythmic activity at a low level is necessary for maintenance of suspended forms of behavior. As glial cells support rhythmic activity of neurons, preservation of brain function in the hibernating state implies accompanying modification of glial activity. A supportive role of glia in regulating neuronal activity is reflected through the activity of inwardly rectifying K+ channels (Kir). Therefore, we examined electrophysiological response, particularly Kir current response, of glial cells in mixture with neurons acutely isolated from active and hibernating land snail Helix pomatia. Our data show that hibernated glia have significantly lower inward current density, specific membrane conductance, and conductance density compared with active glia. The observed reduction could be attributed to the Kir currents, since the Ba2+-sensitive Kir current density was significantly lower in hibernated glia. Accordingly, a significant positive shift of the current reversal potential indicated a more depolarized state of hibernated glia. Data obtained show that modification of glial current response could be regulated by serotonin (5-HT) through an increase of cGMP as a secondary messenger, since extracellular addition of 5-HT or intracellular administration of cGMP to active glia induced a significant reduction of inward current density and thus mimicked the reduced response of hibernated glia. Lower Kir current density of hibernated glia accompanied the lower electrical activity of hibernated neurons, as revealed by a decrease in neuronal fast inward Na+ current density. Our findings reveal that glial response is reduced in the hibernating state and suggest seasonal modulation of glial activity. Maintenance of low glial activity in hibernation could be important for preservation of brain

  17. Distinctive glial and neuronal interfacing on nanocrystalline diamond.

    PubMed

    Bendali, Amel; Agnès, Charles; Meffert, Simone; Forster, Valérie; Bongrain, Alexandre; Arnault, Jean-Charles; Sahel, José-Alain; Offenhäusser, Andreas; Bergonzo, Philippe; Picaud, Serge

    2014-01-01

    Direct electrode/neuron interfacing is a key challenge to achieve high resolution of neuronal stimulation required for visual prostheses. Neuronal interfacing on biomaterials commonly requires the presence of glial cells and/or protein coating. Nanocrystalline diamond is a highly mechanically stable biomaterial with a remarkably large potential window for the electrical stimulation of tissues. Using adult retinal cell cultures from rats, we found that glial cells and retinal neurons grew equally well on glass and nanocrystalline diamond. The use of a protein coating increased cell survival, particularly for glial cells. However, bipolar neurons appeared to grow even in direct contact with bare diamond. We investigated whether the presence of glial cells contributed to this direct neuron/diamond interface, by using purified adult retinal ganglion cells to seed diamond and glass surfaces with and without protein coatings. Surprisingly, these fully differentiated spiking neurons survived better on nanocrystalline diamond without any protein coating. This greater survival was indicated by larger cell numbers and the presence of longer neurites. When a protein pattern was drawn on diamond, neurons did not grow preferentially on the coated area, by contrast to their behavior on a patterned glass. This study highlights the interesting biocompatibility properties of nanocrystalline diamond, allowing direct neuronal interfacing, whereas a protein coating was required for glial cell growth.

  18. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

    PubMed

    Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

    2016-06-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  19. Glial dysfunction causes age-related memory impairment in Drosophila.

    PubMed

    Yamazaki, Daisuke; Horiuchi, Junjiro; Ueno, Kohei; Ueno, Taro; Saeki, Shinjiro; Matsuno, Motomi; Naganos, Shintaro; Miyashita, Tomoyuki; Hirano, Yukinori; Nishikawa, Hiroyuki; Taoka, Masato; Yamauchi, Yoshio; Isobe, Toshiaki; Honda, Yoshiko; Kodama, Tohru; Masuda, Tomoko; Saitoe, Minoru

    2014-11-19

    Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.

  20. Human immunodeficiency virus can productively infect cultured human glial cells.

    PubMed

    Cheng-Mayer, C; Rutka, J T; Rosenblum, M L; McHugh, T; Stites, D P; Levy, J A

    1987-05-01

    Six isolates of the human immunodeficiency virus (HIV) showed differences in their ability to productively infect glioma-derived cell lines and early-passage human brain cell cultures. Susceptibility to HIV infection correlated well with the expression of the astrocyte marker glial fibrillary acidic protein. The CD4 molecule was expressed on some, but not all, of the brain-derived cells; however, no correlation was observed between CD4 protein expression and susceptibility to virus infection. The results show that HIV can productively infect human brain cells, particularly those of glial origin, and suggest that these cell types in the brain can harbor the virus.

  1. Sleep and immune function: glial contributions and consequences of aging.

    PubMed

    Ingiosi, Ashley M; Opp, Mark R; Krueger, James M

    2013-10-01

    The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep. Recent studies indicate that glial cells, namely microglia and astrocytes, are active contributors to sleep and immune system interactions. Evidence suggests glial regulation of these interactions is mediated, in part, by adenosine and adenosine 5'-triphosphate actions at purinergic type 1 and type 2 receptors. Furthermore, microglia and astrocytes may modulate declines in sleep-wake behavior and immunity observed in aging.

  2. 'The patient is medically cleared'.

    PubMed

    Beale, Chloe; Turner, Trevor

    2013-09-01

    It is standard practice for psychiatric nurses and junior doctors working in emergency departments to ask that patients be 'medically cleared' before psychiatric admission or even assessment. However, there is a lack of agreement over what this process should entail.

  3. Transient receptor potential vanilloid 1-immunoreactive signals in murine enteric glial cells

    PubMed Central

    Yamamoto, Masahiro; Nishiyama, Mitsue; Iizuka, Seiichi; Suzuki, Shigeaki; Suzuki, Norihiro; Aiso, Sadakazu; Nakahara, Jin

    2016-01-01

    AIM To investigate the possible involvement of transient receptor potential vanilloid 1 (TRPV1) in maturation of enteric glial cells (EGCs). METHODS Immunohistochemical and immunocytochemical techniques were used to analyze EGC markers in myenteric plexus (MP) as well as cultured MP cells and EGCs using TRPV1 knockout (KO) mice. RESULTS We detected TRPV1-immunoreactive signals in EGC in the MP of wild-type (WT) but not KO mice. Expression of glial fibrillary acidic protein (GFAP) immunoreactive signals was lower at postnatal day (PD) 6 in KO mice, though the difference was not clear at PD 13 and PD 21. When MP cells were isolated and cultured from isolated longitudinal muscle-MP preparation from WT and KO mice, the yield of KO EGC was lower than that of WT EGC, while the yield of KO and WT smooth muscle cells showed no difference. Addition of BCTC, a TRPV1 antagonist, to enriched EGC culture resulted in a decrease in the protein ratio of GFAP to S100B, another EGC/astrocyte-specific marker. CONCLUSION These results address the possibility that TRPV1 may be involved in the maturation of EGC, though further studies are necessary to validate this possibility. PMID:27956799

  4. Glial glucokinase expression in adult and post-natal development of the hypothalamic region.

    PubMed

    Millán, Carola; Martínez, Fernando; Cortés-Campos, Christian; Lizama, Isabel; Yañez, Maria Jose; Llanos, Paula; Reinicke, Karin; Rodríguez, Federico; Peruzzo, Bruno; Nualart, Francisco; García, Maria Angeles

    2010-05-25

    It has recently been proposed that hypothalamic glial cells sense glucose levels and release lactate as a signal to activate adjacent neurons. GK (glucokinase), the hexokinase involved in glucose sensing in pancreatic beta-cells, is also expressed in the hypothalamus. However, it has not been clearly determined if glial and/or neuronal cells express this protein. Interestingly, tanycytes, the glia that cover the ventricular walls of the hypothalamus, are in contact with CSF (cerebrospinal fluid), the capillaries of the arcuate nucleus and adjacent neurons; this would be expected for a system that can detect and communicate changes in glucose concentration. Here, we demonstrated by Western-blot analysis, QRT-PCR [quantitative RT-PCR (reverse transcription-PCR)] and in situ hybridization that GK is expressed in tanycytes. Confocal microscopy and immuno-ultrastructural analysis revealed that GK is localized in the nucleus and cytoplasm of beta1-tanycytes. Furthermore, GK expression increased in these cells during the second week of post-natal development. Based on this evidence, we propose that tanycytes mediate, at least in part, the mechanism by which the hypothalamus detects changes in glucose concentrations.

  5. Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia.

    PubMed

    Zhang, X; Chen, Y; Wang, C; Huang, L-Y M

    2007-06-05

    It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca(2+) entry is required for the release. FM1-43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca(2+) channels completely eliminates the neuron-glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-alpha (TNFalpha) from satellite cells. TNFalpha in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell-cell signaling.

  6. Mechanisms of Aβ Clearance and Degradation by Glial Cells

    PubMed Central

    Ries, Miriam; Sastre, Magdalena

    2016-01-01

    Glial cells have a variety of functions in the brain, ranging from immune defense against external and endogenous hazardous stimuli, regulation of synaptic formation, calcium homeostasis, and metabolic support for neurons. Their dysregulation can contribute to the development of neurodegenerative disorders, including Alzheimer’s disease (AD). One of the most important functions of glial cells in AD is the regulation of Amyloid-β (Aβ) levels in the brain. Microglia and astrocytes have been reported to play a central role as moderators of Aβ clearance and degradation. The mechanisms of Aβ degradation by glial cells include the production of proteases, including neprilysin, the insulin degrading enzyme, and the endothelin-converting enzymes, able to hydrolyse Aβ at different cleavage sites. Besides these enzymes, other proteases have been described to have some role in Aβ elimination, such as plasminogen activators, angiotensin-converting enzyme, and matrix metalloproteinases. Other relevant mediators that are released by glial cells are extracellular chaperones, involved in the clearance of Aβ alone or in association with receptors/transporters that facilitate their exit to the blood circulation. These include apolipoproteins, α2macroglobulin, and α1-antichymotrypsin. Finally, astrocytes and microglia have an essential role in phagocytosing Aβ, in many cases via a number of receptors that are expressed on their surface. In this review, we examine all of these mechanisms, providing an update on the latest research in this field. PMID:27458370

  7. Understanding the NG2 Glial Scar after Spinal Cord Injury

    PubMed Central

    Hackett, Amber R.; Lee, Jae K.

    2016-01-01

    NG2 cells, also known as oligodendrocyte progenitor cells, are located throughout the central nervous system and serve as a pool of progenitors to differentiate into oligodendrocytes. In response to spinal cord injury (SCI), NG2 cells increase their proliferation and differentiation into remyelinating oligodendrocytes. While astrocytes are typically associated with being the major cell type in the glial scar, many NG2 cells also accumulate within the glial scar but their function remains poorly understood. Similar to astrocytes, these cells hypertrophy, upregulate expression of chondroitin sulfate proteoglycans, inhibit axon regeneration, contribute to the glial-fibrotic scar border, and some even differentiate into astrocytes. Whether NG2 cells also have a role in other astrocyte functions, such as preventing the spread of infiltrating leukocytes and expression of inflammatory cytokines, is not yet known. Thus, NG2 cells are not only important for remyelination after SCI but are also a major component of the glial scar with functions that overlap with astrocytes in this region. In this review, we describe the signaling pathways important for the proliferation and differentiation of NG2 cells, as well as the role of NG2 cells in scar formation and tissue repair. PMID:27895617

  8. Glial progenitor cell-based treatment of the childhood leukodystrophies

    PubMed Central

    Osorio, M. Joana; Goldman, Steven A.

    2017-01-01

    The childhood leukodystrophies comprise a group of hereditary disorders characterized by the absence, malformation or destruction of myelin. These disorders share common clinical, radiological and pathological features, despite their diverse molecular and genetic etiologies. Oligodendrocytes and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group of non-lysosomal metabolic leukodystrophies, may all be appropriate candidates for glial progenitor cell-based treatment. Nonetheless, a variety of specific challenges remain before this therapeutic strategy can be applied to children. These include timely diagnosis, before irreparable neuronal injury has ensued; understanding the natural history of the targeted disease; defining the optimal cell phenotype for each disorder; achieving safe and scalable cellular compositions, designing age-appropriate controlled clinical trials; and for autologous therapy of genetic disorders, achieving the safe genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease. PMID:27170209

  9. Neuronal Injury and Glial Changes Are Hallmarks of Open Field Blast Exposure in Swine Frontal Lobe

    PubMed Central

    Kallakuri, Srinivasu; Desai, Alok; Feng, Ke; Tummala, Sharvani; Saif, Tal; Chen, Chaoyang; Zhang, Liying; Cavanaugh, John M.; King, Albert I.

    2017-01-01

    With the rapid increase in the number of blast induced traumatic brain injuries and associated neuropsychological consequences in veterans returning from the operations in Iraq and Afghanistan, the need to better understand the neuropathological sequelae following exposure to an open field blast exposure is still critical. Although a large body of experimental studies have attempted to address these pathological changes using shock tube models of blast injury, studies directed at understanding changes in a gyrencephalic brain exposed to a true open field blast are limited and thus forms the focus of this study. Anesthetized, male Yucatan swine were subjected to forward facing medium blast overpressure (peak side on overpressure 224–332 kPa; n = 7) or high blast overpressure (peak side on overpressure 350–403 kPa; n = 5) by detonating 3.6 kg of composition-4 charge. Sham animals (n = 5) were subjected to all the conditions without blast exposure. After a 3-day survival period, the brain was harvested and sections from the frontal lobes were processed for histological assessment of neuronal injury and glial reactivity changes. Significant neuronal injury in the form of beta amyloid precursor protein immunoreactive zones in the gray and white matter was observed in the frontal lobe sections from both the blast exposure groups. A significant increase in the number of astrocytes and microglia was also observed in the blast exposed sections compared to sham sections. We postulate that the observed acute injury changes may progress to chronic periods after blast and may contribute to short and long-term neuronal degeneration and glial mediated inflammation. PMID:28107370

  10. Neuronal Injury and Glial Changes Are Hallmarks of Open Field Blast Exposure in Swine Frontal Lobe.

    PubMed

    Kallakuri, Srinivasu; Desai, Alok; Feng, Ke; Tummala, Sharvani; Saif, Tal; Chen, Chaoyang; Zhang, Liying; Cavanaugh, John M; King, Albert I

    2017-01-01

    With the rapid increase in the number of blast induced traumatic brain injuries and associated neuropsychological consequences in veterans returning from the operations in Iraq and Afghanistan, the need to better understand the neuropathological sequelae following exposure to an open field blast exposure is still critical. Although a large body of experimental studies have attempted to address these pathological changes using shock tube models of blast injury, studies directed at understanding changes in a gyrencephalic brain exposed to a true open field blast are limited and thus forms the focus of this study. Anesthetized, male Yucatan swine were subjected to forward facing medium blast overpressure (peak side on overpressure 224-332 kPa; n = 7) or high blast overpressure (peak side on overpressure 350-403 kPa; n = 5) by detonating 3.6 kg of composition-4 charge. Sham animals (n = 5) were subjected to all the conditions without blast exposure. After a 3-day survival period, the brain was harvested and sections from the frontal lobes were processed for histological assessment of neuronal injury and glial reactivity changes. Significant neuronal injury in the form of beta amyloid precursor protein immunoreactive zones in the gray and white matter was observed in the frontal lobe sections from both the blast exposure groups. A significant increase in the number of astrocytes and microglia was also observed in the blast exposed sections compared to sham sections. We postulate that the observed acute injury changes may progress to chronic periods after blast and may contribute to short and long-term neuronal degeneration and glial mediated inflammation.

  11. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model.

    PubMed

    Borges, Karin; Gearing, Marla; McDermott, Dayna L; Smith, Amy B; Almonte, Antoine G; Wainer, Bruce H; Dingledine, Raymond

    2003-07-01

    The rodent pilocarpine model of epilepsy exhibits hippocampal sclerosis and spontaneous seizures and thus resembles human temporal lobe epilepsy. Use of the many available mouse mutants to study this epilepsy model would benefit from a detailed neuropathology study. To identify new features of epileptogenesis, we characterized glial and neuronal pathologies after pilocarpine-induced status epilepticus (SE) in CF1 and C57BL/6 mice focusing on the hippocampus. All CF1 mice showed spontaneous seizures by 17-27 days after SE. By 6 h there was virtually complete loss of hilar neurons, but the extent of pyramidal cell death varied considerably among mice. In the mossy fiber pathway, neuropeptide Y (NPY) was persistently upregulated beginning 1 day after SE; NPY immunoreactivity in the supragranular layer after 31 days indicated mossy fiber sprouting. beta2 microglobulin-positive activated microglia, normally absent in brains without SE, became abundant over 3-31 days in regions of neuronal loss, including the hippocampus and the amygdala. Astrogliosis developed after 10 days in damaged areas. Amyloid precursor protein immunoreactivity in the thalamus at 10 days suggested delayed axonal degeneration. The mortality after pilocarpine injection was very high in C57BL/6 mice from Jackson Laboratories but not those from Charles River, suggesting that mutant mice in the C57BL/6(JAX) strain will be difficult to study in the pilocarpine model, although their neuropathology was similar to CF1 mice. Major neuropathological changes not previously studied in the rodent pilocarpine model include widespread microglial activation, delayed thalamic axonal death, and persistent NPY upregulation in mossy fibers, together revealing extensive and persistent glial as well as neuronal pathology.

  12. Effects of Cadmium on the Glial Architecture in Lizard Brain

    PubMed Central

    Favorito, Rossana; Monaco, Antonio; Grimaldi, Maria C.; Ferrandino, Ida

    2017-01-01

    The glial cells are positioned to be the first cells of the brain parenchyma to face molecules crossing the blood-brain barrier with a relevant neuroprotective role from cytotoxic action of heavy metals on the nervous system. Cadmium is a highly toxic metal and its levels in the environment are increasing due to industrial activities. This element can pass the blood-brain barrier and have neurotoxic activity. For this reason we have studied the effects of cadmium on the glial architecture in the lizard Podarcis siculus, a significant bioindicator of chemical exposure due to its persistence in a variety of habitats. The study was performed on two groups of lizards. The first group of P. siculus was exposed to an acute treatment by a single i.p. injection (2 mg/kg-BW) of CdCl2 and sacrificed after 2, 7 and 16 days. The second one was used as control. The histology of the brain was studied by Hematoxylin/Eosin and Cresyl/Violet stains while the glial structures were analyzed by immunodetection of the glial fibrillary acidic protein (GFAP), the most widely accepted marker for astroglial cells. Evident morphological alterations of the brain were observed at 7 and 16 days from the injection, when we revealed also a decrease of the GFAP-immunopositive structures in particular in the rhombencephalic ventricle, telencephalon and optic tectum. These results show that in the lizards an acute exposure to cadmium provokes morphological cellular alterations in the brain but also a decrement of the expression of GFAP marker with possible consequent damage of glial cells functions. PMID:28348417

  13. CLEAR LAKE ROADLESS AREA, FLORIDA.

    USGS Publications Warehouse

    Patterson, Sam H.; Crandall, Thomas M.

    1984-01-01

    On the basis of a mineral survey the Clear Lake Roadless Area, Florida was concluded to offer little or no promise for the occurrence of mineral resources. The only commodity that has been mined in the area is clayey sand used in stabilizing roads and in highway construction. No peat more than a few inches thick occurs in the area. Limestone underlies all of the Clear Lake area but is under thick overburden. The region has been explored for heavy minerals and phosphate, but no resources have been found. There appears to be little promise for discovery of oil and gas in the Clear Lake area. However, the area and nearby lands have not been thoroughly tested for oil and gas, and the possibilities for discovery cannot be ruled out.

  14. Immunolocalization of membrane skeletal protein, 4.1G, in enteric glial cells in the mouse large intestine.

    PubMed

    Chen, Jiaorong; Terada, Nobuo; Ohno, Nobuhiko; Saitoh, Sei; Saitoh, Yurika; Ohno, Shinichi

    2011-01-20

    4.1 family proteins are membrane skeletal proteins that interact with spectrin-actin networks and intramembraneous proteins. We reported that one of them, 4.1G, was immunolocalized in myelinated nerve fibers of the mouse peripheral nervous system, especially along cell membranes of paranodes and Schmidt-Lanterman incisures in Schwann cells. In this study, to examine 4.1G's appearance in unmyelinated peripheral nerve fibers, we focused on the enteric nervous system in mouse large intestines. In intestinal tissues prepared by an "in vivo cryotechnique" followed by freeze-substitution fixation, 4.1G was immunolocalized in Auerbach's myenteric plexus and connecting nerve fiber networks. Its immunostaining was mostly colocalized with glial fibrillar acidic protein, a marker of enteric glial cells, but not with c-Kit, a marker of interstitial cells of Cajal. Using whole-mount preparation after splitting inner and outer muscle layers, the nerve fiber networks including the plexus were clearly detected by the 4.1G immunostaining. By conventional pre-embedding immunoelectron microscopy, 4.1G was detected along cell membranes of enteric glial cells and their processes surrounding axons. These indicate that 4.1G may have some roles in adhesion and/or signal transduction in unmylinated PNS nerve fibers.

  15. Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons.

    PubMed

    Proschel, Christoph; Stripay, Jennifer L; Shih, Chung-Hsuan; Munger, Joshua C; Noble, Mark D

    2014-04-01

    In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically-relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDAs(BMP), that are generated in vitro by directed differentiation of glial precursors. GDAs(BMP) produce multiple agents of interest as treatments for PD and other neurodegenerative disorders, including BDNF, GDNF, neurturin and IGF1. GDAs(BMP) also exhibit increased levels of antioxidant pathway components, including levels of NADPH and glutathione. Delayed GDA(BMP) transplantation into the 6-hydroxydopamine lesioned rat striatum restored tyrosine hydroxylase expression and promoted behavioral recovery. GDA(BMP) transplantation also rescued pathological changes not prevented in other studies, such as the rescue of parvalbumin(+) GABAergic interneurons. Consistent with expression of the synaptic modulatory proteins thrombospondin-1 and 2 by GDAs(BMP), increased expression of the synaptic protein synaptophysin was also observed. Thus, GDAs(BMP) offer a multimodal support cell therapy that provides multiple benefits without requiring prior genetic manipulation.

  16. Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons

    PubMed Central

    Proschel, Christoph; Stripay, Jennifer L; Shih, Chung-Hsuan; Munger, Joshua C; Noble, Mark D

    2014-01-01

    In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically-relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDAsBMP, that are generated in vitro by directed differentiation of glial precursors. GDAsBMP produce multiple agents of interest as treatments for PD and other neurodegenerative disorders, including BDNF, GDNF, neurturin and IGF1. GDAsBMP also exhibit increased levels of antioxidant pathway components, including levels of NADPH and glutathione. Delayed GDABMP transplantation into the 6-hydroxydopamine lesioned rat striatum restored tyrosine hydroxylase expression and promoted behavioral recovery. GDABMP transplantation also rescued pathological changes not prevented in other studies, such as the rescue of parvalbumin+ GABAergic interneurons. Consistent with expression of the synaptic modulatory proteins thrombospondin-1 and 2 by GDAsBMP, increased expression of the synaptic protein synaptophysin was also observed. Thus, GDAsBMP offer a multimodal support cell therapy that provides multiple benefits without requiring prior genetic manipulation. PMID:24477866

  17. RNA Methylation Clears the Way.

    PubMed

    Kontur, Cassandra; Giraldez, Antonio

    2017-03-13

    During the maternal-to-zygotic transition, maternal mRNAs are cleared by multiple distinct but interrelated pathways. A recent study in Nature by Zhao et al. (2017) finds that YTHDF2, a reader of N(6)- methylation, facilitates maternal mRNA decay, introducing an additional facet of control over transcript fate and developmental reprogramming.

  18. Development of a glial network in the olfactory nerve: role of calcium and neuronal activity.

    PubMed

    Koussa, Mounir A; Tolbert, Leslie P; Oland, Lynne A

    2010-11-01

    In adult olfactory nerves of mammals and moths, a network of glial cells ensheathes small bundles of olfactory receptor axons. In the developing antennal nerve (AN) of the moth Manduca sexta, the axons of olfactory receptor neurons (ORNs) migrate from the olfactory sensory epithelium toward the antennal lobe. Here we explore developmental interactions between ORN axons and AN glial cells. During early stages in AN glial-cell migration, glial cells are highly dye coupled, dividing glia are readily found in the nerve and AN glial cells label strongly for glutamine synthetase. By the end of this period, dye-coupling is rare, glial proliferation has ceased, glutamine synthetase labeling is absent, and glial processes have begun to extend to enwrap bundles of axons, a process that continues throughout the remainder of metamorphic development. Whole-cell and perforated-patch recordings in vivo from AN glia at different stages of network formation revealed two potassium currents and an R-like calcium current. Chronic in vivo exposure to the R-type channel blocker SNX-482 halted or greatly reduced AN glial migration. Chronically blocking spontaneous Na-dependent activity by injection of tetrodotoxin reduced the glial calcium current implicating an activity-dependent interaction between ORNs and glial cells in the development of glial calcium currents.

  19. Ideas for clear technical writing

    USGS Publications Warehouse

    Robinson, B.P.

    1984-01-01

    The three greatest obstacles to clear technical-report writing are probably (1) imprecise words, (2) wordiness, and (3) poorly constructed sentences. Examples of category 1 include abstract words, jargon, and vogue words; of category 2, sentences containing impersonal construction superfluous words; and of category 3, sentences lacking parallel construction and proper order of related words and phrases. These examples and other writing-related subjects are discussed in the report, which contains a cross-referenced index and 24 references.

  20. CLEAR LAKE BASIN 2000 PROJECT

    SciTech Connect

    LAKE COUNTY SANITATION DISTRICT

    2003-03-31

    The following is a final report for the Clear Lake Basin 2000 project. All of the major project construction work was complete and this phase generally included final details and testing. Most of the work was electrical. Erosion control activities were underway to prepare for the rainy season. System testing including pump stations, electrical and computer control systems was conducted. Most of the project focus from November onward was completing punch list items.

  1. 77 FR 21277 - Customer Clearing Documentation, Timing of Acceptance for Clearing, and Clearing Member Risk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-09

    ...The Commodity Futures Trading Commission (``Commission'' or ``CFTC'') is adopting rules to implement new statutory provisions enacted by Title VII of the Dodd-Frank Wall Street Reform and Consumer Protection Act. These rules address: The documentation between a customer and a futures commission merchant that clears on behalf of the customer; the timing of acceptance or rejection of trades for......

  2. The EM Earthquake Precursor

    NASA Astrophysics Data System (ADS)

    Jones, K. B., II; Saxton, P. T.

    2013-12-01

    Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After the 1989 Loma Prieta Earthquake, American earthquake investigators predetermined magnetometer use and a minimum earthquake magnitude necessary for EM detection. This action was set in motion, due to the extensive damage incurred and public outrage concerning earthquake forecasting; however, the magnetometers employed, grounded or buried, are completely subject to static and electric fields and have yet to correlate to an identifiable precursor. Secondly, there is neither a networked array for finding any epicentral locations, nor have there been any attempts to find even one. This methodology needs dismissal, because it is overly complicated, subject to continuous change, and provides no response time. As for the minimum magnitude threshold, which was set at M5, this is simply higher than what modern technological advances have gained. Detection can now be achieved at approximately M1, which greatly improves forecasting chances. A propagating precursor has now been detected in both the field and laboratory. Field antenna testing conducted outside the NE Texas town of Timpson in February, 2013, detected three strong EM sources along with numerous weaker signals. The antenna had mobility, and observations were noted for recurrence, duration, and frequency response. Next, two

  3. Satellite glial cells in sensory ganglia: from form to function.

    PubMed

    Hanani, Menachem

    2005-06-01

    Current information indicates that glial cells participate in all the normal and pathological processes of the central nervous system. Although much less is known about satellite glial cells (SGCs) in sensory ganglia, it appears that these cells share many characteristics with their central counterparts. This review presents information that has been accumulated recently on the physiology and pharmacology of SGCs. It appears that SGCs carry receptors for numerous neuroactive agents (e.g., ATP, bradykinin) and can therefore receive signals from other cells and respond to changes in their environment. Activation of SGCs might in turn influence neighboring neurons. Thus SGCs are likely to participate in signal processing and transmission in sensory ganglia. Damage to the axons of sensory ganglia is known to contribute to neuropathic pain. Such damage also affects SGCs, and it can be proposed that these cells have a role in pathological changes in the ganglia.

  4. Temporal Variant Frontotemporal Dementia is Associated with Globular Glial Tauopathy.

    PubMed

    Clark, Camilla N; Lashley, Tammaryn; Mahoney, Colin J; Warren, Jason D; Revesz, Tamas; Rohrer, Jonathan D

    2015-06-01

    Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative disorder associated with atrophy of the frontal and temporal lobes. Most patients with focal temporal lobe atrophy present with either the semantic dementia subtype of FTD or the behavioral variant subtype. For patients with temporal variant FTD, the most common cause found on post-mortem examination has been a TDP-43 (transactive response DNA-binding protein 43 kDa) proteinopathy, but tauopathies have also been described, including Pick's disease and mutations in the microtubule-associated protein tau (MAPT) gene. We report the clinical and imaging features of 2 patients with temporal variant FTD associated with a rare frontotemporal lobar degeneration pathology known as globular glial tauopathy. The pathologic diagnosis of globular glial tauopathy should be considered in patients with temporal variant FTD, particularly those who have atypical semantic dementia or an atypical parkinsonian syndrome in association with the right temporal variant.

  5. Glial β-oxidation regulates Drosophila energy metabolism.

    PubMed

    Schulz, Joachim G; Laranjeira, Antonio; Van Huffel, Leen; Gärtner, Annette; Vilain, Sven; Bastianen, Jarl; Van Veldhoven, Paul P; Dotti, Carlos G

    2015-01-15

    The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production.

  6. Glial β-Oxidation regulates Drosophila Energy Metabolism

    PubMed Central

    Schulz, Joachim G.; Laranjeira, Antonio; Van Huffel, Leen; Gärtner, Annette; Vilain, Sven; Bastianen, Jarl; Van Veldhoven, Paul P.; Dotti, Carlos G.

    2015-01-01

    The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production. PMID:25588812

  7. Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis

    PubMed Central

    Alshikho, Mohamad J.; Zürcher, Nicole R.; Loggia, Marco L.; Cernasov, Paul; Chonde, Daniel B.; Izquierdo Garcia, David; Yasek, Julia E.; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R.; Cudkowicz, Merit E.

    2016-01-01

    Objective: In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Methods: Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [11C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [11C]-PBR28 uptake. Results: In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [11C]-PBR28 binding in the left motor cortex was correlated with FA (r = −0.68, p < 0.05) and cortical thickness (r = −0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = −0.77, p < 0.05), and cortical thickness (r = −0.75, p < 0.05) in the motor cortex. Conclusions: Increased uptake of the glial marker [11C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. PMID:27837005

  8. Glial Modulators as Potential Treatments of Psychostimulant Abuse

    PubMed Central

    Beardsley, Patrick M.; Hauser, Kurt F.

    2014-01-01

    Glia (including astrocytes, microglia and oligodendrocytes), which constitute the majority of cells in the brain. have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mid-1800s, and only relatively recently have they been gaining their due respect. This development of appreciation has been nurtured by the growing awareness that drugs of abuse, including the psychostimulants, affect glial activity, and glial activity, in turn, has been found to modulate the effects of the psychostimulants. This developing awareness has begun to illuminate novel pharmacotherapeutic targets for treating psychostimulant abuse, for which targeting more conventional neuronal targets has not yet resulted in a single, approved medication. In this chapter, we discuss the molecular pharmacology, physiology and functional relationships that the glia have especially in the light in which they present themselves as targets for pharmacotherapeutics intended to treat psychostimulant abuse disorders. We then review a cross section of preclinical studies that have manipulated glial processes whose behavioral effects have been supportive of considering the glia as drug targets for psychostimulant-abuse medications. We then close with comments regarding the current clinical evaluation of relevant compounds for treating psychostimulant abuse, as well as the likelihood of future prospects. PMID:24484974

  9. Homocysteine Induces Glial Reactivity in Adult Rat Astrocyte Cultures.

    PubMed

    Longoni, Aline; Bellaver, Bruna; Bobermin, Larissa Daniele; Santos, Camila Leite; Nonose, Yasmine; Kolling, Janaina; Dos Santos, Tiago M; de Assis, Adriano M; Quincozes-Santos, André; Wyse, Angela T S

    2017-03-02

    Astrocytes are dynamic glial cells associated to neurotransmitter systems, metabolic functions, antioxidant defense, and inflammatory response, maintaining the brain homeostasis. Elevated concentrations of homocysteine (Hcy) are involved in the pathogenesis of age-related neurodegenerative disorders, such as Parkinson and Alzheimer diseases. In line with this, our hypothesis was that Hcy could promote glial reactivity in a model of cortical primary astrocyte cultures from adult Wistar rats. Thus, cortical astrocytes were incubated with different concentrations of Hcy (10, 30, and 100 μM) during 24 h. After the treatment, we analyzed cell viability, morphological parameters, antioxidant defenses, and inflammatory response. Hcy did not induce any alteration in cell viability; however, it was able to induce cytoskeleton rearrangement. The treatment with Hcy also promoted a significant decrease in the activities of Na(+), K(+) ATPase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as in the glutathione (GSH) content. Additionally, Hcy induced an increase in the pro-inflammatory cytokine release. In an attempt to elucidate the putative mechanisms involved in the Hcy-induced glial reactivity, we measured the nuclear factor kappa B (NFκB) transcriptional activity and heme oxygenase 1 (HO-1) expression, which were activated and inhibited by Hcy, respectively. In summary, our findings provide important evidences that Hcy modulates critical astrocyte parameters from adult rats, which might be associated to the aging process.

  10. Glial modulators as potential treatments of psychostimulant abuse.

    PubMed

    Beardsley, Patrick M; Hauser, Kurt F

    2014-01-01

    Glia (including astrocytes, microglia, and oligodendrocytes), which constitute the majority of cells in the brain, have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mid-1800s, and only relatively recently have they been gaining their due respect. This development of appreciation has been nurtured by the growing awareness that drugs of abuse, including the psychostimulants, affect glial activity, and glial activity, in turn, has been found to modulate the effects of the psychostimulants. This developing awareness has begun to illuminate novel pharmacotherapeutic targets for treating psychostimulant abuse, for which targeting more conventional neuronal targets has not yet resulted in a single, approved medication. In this chapter, we discuss the molecular pharmacology, physiology, and functional relationships that the glia have especially in the light in which they present themselves as targets for pharmacotherapeutics intended to treat psychostimulant abuse disorders. We then review a cross section of preclinical studies that have manipulated glial processes whose behavioral effects have been supportive of considering the glia as drug targets for psychostimulant-abuse medications. We then close with comments regarding the current clinical evaluation of relevant compounds for treating psychostimulant abuse, as well as the likelihood of future prospects.

  11. Transcriptional regulation of the Drosophila glial gene repo.

    PubMed

    Lee, Bruce P; Jones, Bradley W

    2005-06-01

    reversed polarity (repo) is a putative target gene of glial cells missing (gcm), the primary regulator of glial cell fate in Drosophila. Transient expression of Gcm is followed by maintained expression of repo. Multiple Gcm binding sites are found in repo upstream DNA. However, while repo is expressed in Gcm positive glia, it is not expressed in Gcm positive hemocytes. These observations suggest factors in addition to Gcm are required for repo expression. Here we have undertaken an analysis of the cis-regulatory DNA elements of repo using lacZ reporter activity in transgenic embryos. We have found that a 4.2 kb DNA region upstream of the repo start site drives the wild-type repo expression pattern. We show that expression is dependent on multiple Gcm binding sites. By ectopically expressing Repo, we show that Repo can regulate its own enhancer. Finally, by systematically analyzing fragments of repo upstream DNA, we show that expression is dependent on multiple elements that are responsible for activity in subsets of glia, as well as repressing inappropriate expression in the epidermis. Our results suggest that Gcm acts synergistically with other factors to control repo transcription in glial cells.

  12. Io's Sodium Cloud (Clear Filter)

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This image of Jupiter's moon Io and its surrounding sky is shown in false color. It was taken at 5 hours 30 minutes Universal Time on Nov. 9, 1996 by the solid state imaging (CCD) system aboard NASA's Galileo spacecraft, using a clear filter whose wavelength range was approximately 400 to 1100 nanometers. This picture differs in two main ways from the green-yellow filter image of the same scene which was released yesterday.

    First, the sky around Io is brighter, partly because the wider wavelength range of the clear filter lets in more scattered light from Io's illuminated crescent and from Prometheus' sunlit plume. Nonetheless, the overall sky brightness in this frame is comparable to that seen through the green-yellow filter, indicating that even here much of the diffuse sky emission is coming from the wavelength range of the green-yellow filter (i.e., from Io's Sodium Cloud).

    The second major difference is that a quite large roundish spot has appeared in Io's southern hemisphere. This spot -- which has been colored red -- corresponds to thermal emission from the volcano Pele. The green-yellow filter image bears a much smaller trace of this emission because the clear filter is far more sensitive to those relatively long wavelengths where thermal emission is strongest.

    The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

  13. Chamber Clearing First Principles Modeling

    SciTech Connect

    Loosmore, G

    2009-06-09

    LIFE fusion is designed to generate 37.5 MJ of energy per shot, at 13.3 Hz, for a total average fusion power of 500 MW. The energy from each shot is partitioned among neutrons ({approx}78%), x-rays ({approx}12%), and ions ({approx}10%). First wall heating is dominated by x-rays and debris because the neutron mean free path is much longer than the wall thickness. Ion implantation in the first wall also causes damage such as blistering if not prevented. To moderate the peak-pulse heating, the LIFE fusion chamber is filled with a gas (such as xenon) to reduce the peak-pulse heat load. The debris ions and majority of the x-rays stop in the gas, which re-radiates this energy over a longer timescale (allowing time for heat conduction to cool the first wall sufficiently to avoid damage). After a shot, because of the x-ray and ion deposition, the chamber fill gas is hot and turbulent and contains debris ions. The debris needs to be removed. The ions increase the gas density, may cluster or form aerosols, and can interfere with the propagation of the laser beams to the target for the next shot. Moreover, the tritium and high-Z hohlraum debris needs to be recovered for reuse. Additionally, the cryogenic target needs to survive transport through the gas mixture to the chamber center. Hence, it will be necessary to clear the chamber of the hot contaminated gas mixture and refill it with a cool, clean gas between shots. The refilling process may create density gradients that could interfere with beam propagation, so the fluid dynamics must be studied carefully. This paper describes an analytic modeling effort to study the clearing and refilling process for the LIFE fusion chamber. The models used here are derived from first principles and balances of mass and energy, with the intent of providing a first estimate of clearing rates, clearing times, fractional removal of ions, equilibrated chamber temperatures, and equilibrated ion concentrations for the chamber. These can be used

  14. Glutamate-dependent ectodomain shedding of neuregulin-1 type II precursors in rat forebrain neurons

    PubMed Central

    Iwakura, Yuriko; Wang, Ran; Inamura, Naoko; Araki, Kazuaki; Higashiyama, Shigeki; Takei, Nobuyuki; Nawa, Hiroyuki

    2017-01-01

    The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells. Using a two-site enzyme immunoassay to detect soluble NRG1, we show that, of various neurotransmitters, glutamate was the most potent inducer of NRG1 release in neuron-enriched cultures. NRG1 release in glia-enriched cultures was relatively limited. Furthermore, among glutamate receptor agonists, N-Methyl-D-Aspartate (NMDA) and kainate (KA), but not AMPA or tACPD, mimicked the effects of glutamate. Similar findings were acquired from analysis of the hippocampus of rats with KA-induced seizures. To evaluate the contribution of members of a disintegrin and metalloproteinase (ADAM) families to NRG1 release, we transfected primary cultures of neurons with cDNA vectors encoding NRG1 types I, II, or III precursors, each tagged with the alkaline phosphatase reporter. Analysis of alkaline phosphatase activity revealed that the NRG1 type II precursor was subjected to tumor necrosis factor-α-converting enzyme (TACE) / a Disintegrin And Metalloproteinase 17 (ADAM17) -dependent ectodomain shedding in a protein kinase C-dependent manner. These results suggest that glutamatergic neurotransmission positively regulates the ectodomain shedding of NRG1 type II precursors and liberates the active NRG1 domain in an activity-dependent manner. PMID:28350885

  15. The heme precursor delta-aminolevulinate blocks peripheral myelin formation

    PubMed Central

    Felitsyn, Natalia; McLeod, Colin; Shroads, Albert L.; Stacpoole, Peter W.; Notterpek, Lucia

    2008-01-01

    Delta-aminolevulinic acid (δ-ALA) is a heme precursor implicated in neurological complications associated with porphyria and tyrosinemia type I. Delta-ALA is also elevated in the urine of animals and patients treated with the investigational drug dichloroacetate (DCA). We postulated that δ-ALA may be responsible, in part, for the peripheral neuropathy observed in subjects receiving DCA. To test this hypothesis, myelinating cocultures of Schwann cells and sensory neurons were exposed to δ-ALA (0.1–1 mM) and analyzed for the expression of neural proteins and lipids and markers of oxidative stress. Exposure of myelinating samples to δ-ALA is associated with a pronounced reduction in the levels of myelin-associated lipids and proteins, including myelin protein zero and peripheral myelin protein 22. We also observed an increase in protein carbonylation and the formation of hydroxynonenal and malondialdehyde after treatment with δ-ALA. Studies of isolated Schwann cells and neurons indicate that glial cells are more vulnerable to this pro-oxidant than neurons, based on a selective decrease in the expression of mitochondrial respiratory chain proteins in glial, but not in neuronal, cells. These results suggest that the neuropathic effects of δ-ALA are attributable, at least in part, to its pro-oxidant properties which damage myelinating Schwann cells. PMID:18665889

  16. Role of satellite glial cells in gastrointestinal pain.

    PubMed

    Hanani, Menachem

    2015-01-01

    Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons in rodent DRG become hyperexcitable in models of GI pain (e.g., gastric or colonic inflammation), and can serve as a source for chronic pain. Glial cells are another element in the pain signaling pathways, and there is evidence that spinal glial cells (microglia and astrocytes) undergo activation (gliosis) in various pain models and contribute to pain. Recently it was found that satellite glial cells (SGCs), the main type of glial cells in sensory ganglia, might also contribute to chronic pain in rodent models. Most of that work focused on somatic pain, but in several studies GI pain was also investigated, and these are discussed in the present review. We have shown that colonic inflammation induced by dinitrobenzene sulfonic acid (DNBS) in mice leads to the activation of SGCs in DRG and increases gap junction-mediated coupling among these cells. This coupling appears to contribute to the hyperexcitability of DRG neurons that innervate the colon. Blocking gap junctions (GJ) in vitro reduced neuronal hyperexcitability induced by inflammation, suggesting that glial GJ participate in SGC-neuron interactions. Moreover, blocking GJ by carbenoxolone and other agents reduces pain behavior. Similar changes in SGCs were also found in the mouse nodose ganglia (NG), which provide sensory innervation to most of the GI tract. Following systemic inflammation, SGCs in these ganglia were activated, and displayed augmented coupling and greater sensitivity to the pain mediator ATP. The contribution of these changes to visceral pain remains to be determined. These results indicate that although visceral pain is unique, it shares basic mechanisms with somatic pain

  17. Role of satellite glial cells in gastrointestinal pain

    PubMed Central

    Hanani, Menachem

    2015-01-01

    Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons in rodent DRG become hyperexcitable in models of GI pain (e.g., gastric or colonic inflammation), and can serve as a source for chronic pain. Glial cells are another element in the pain signaling pathways, and there is evidence that spinal glial cells (microglia and astrocytes) undergo activation (gliosis) in various pain models and contribute to pain. Recently it was found that satellite glial cells (SGCs), the main type of glial cells in sensory ganglia, might also contribute to chronic pain in rodent models. Most of that work focused on somatic pain, but in several studies GI pain was also investigated, and these are discussed in the present review. We have shown that colonic inflammation induced by dinitrobenzene sulfonic acid (DNBS) in mice leads to the activation of SGCs in DRG and increases gap junction-mediated coupling among these cells. This coupling appears to contribute to the hyperexcitability of DRG neurons that innervate the colon. Blocking gap junctions (GJ) in vitro reduced neuronal hyperexcitability induced by inflammation, suggesting that glial GJ participate in SGC-neuron interactions. Moreover, blocking GJ by carbenoxolone and other agents reduces pain behavior. Similar changes in SGCs were also found in the mouse nodose ganglia (NG), which provide sensory innervation to most of the GI tract. Following systemic inflammation, SGCs in these ganglia were activated, and displayed augmented coupling and greater sensitivity to the pain mediator ATP. The contribution of these changes to visceral pain remains to be determined. These results indicate that although visceral pain is unique, it shares basic mechanisms with somatic pain

  18. Relationship between glial potassium regulation and axon excitability: a role for glial Kir4.1 channels.

    PubMed

    Bay, Virginia; Butt, Arthur M

    2012-04-01

    Uptake of K(+) released by axons during action potential propagation is a major function of astrocytes. Here, we demonstrate the importance of glial inward rectifying potassium channels (Kir) in regulating extracellular K(+) ([K(+)](o)) and axonal electrical activity in CNS white matter of the mouse optic nerve. Increasing optic nerve stimulation frequency from 1 Hz to 10-35 Hz for 120 s resulted in a rise in [K(+)](o) and consequent decay in the compound action potential (CAP), a measure of reduced axonal activity. On cessation of high frequency stimulation, rapid K(+) clearance resulted in a poststimulus [K(+)](o) undershoot, followed by a slow recovery of [K(+)](o) and the CAP, which were more protracted with increasing stimulation frequency. Blockade of Kir (100 μM BaCl(2)) slowed poststimulus recovery of [K(+)](o) and the CAP at all stimulation frequencies, indicating a primary function of glial Kir was redistributing K(+) to the extracellular space to offset active removal by Na(+)-K(+) pumps. At higher levels of axonal activity, Kir blockade also increased [K(+)](o) accumulation, exacerbating the decline in the CAP and impeding its subsequent recovery. In the Kir4.1-/- mouse, astrocytes displayed a marked reduction of inward currents and were severely depolarized, resulting in retarded [K(+)](o) regulation and reduced CAP. The results demonstrate the importance of glial Kir in K(+) spatial buffering and sustaining axonal activity in the optic nerve. Glial Kir have increasing importance in K(+) clearance at higher levels of axonal activity, helping to maintain the physiological [K(+)](o) ceiling and ensure the fidelity of signaling between the retina and brain.

  19. NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration

    PubMed Central

    Kang, Shin H.; Fukaya, Masahiro; Yang, Jason K.; Rothstein, Jeffrey D.; Bergles, Dwight E.

    2010-01-01

    SUMMARY The mammalian CNS contains a ubiquitous population of glial progenitors known as NG2+ cells that have the ability to develop into oligodendrocytes and undergo dramatic changes in response to injury and demyelination. Although it has been reported that NG2+ cells are multipotent, their fate in health and disease remains controversial. Here, we generated PDGFαR-CreER transgenic mice and followed their fate in vivo in the developing and adult CNS. These studies revealed that NG2+ cells in the postnatal CNS generate myelinating oligodendrocytes, but not astrocytes or neurons. In regions of neurodegeneration in the spinal cord of ALS mice, NG2+ cells exhibited enhanced proliferation and accelerated differentiation into oligodendrocytes, but remained committed to the oligodendrocyte lineage. These results indicate that NG2+ cells in the normal CNS are oligodendrocyte precursors with restricted lineage potential, and that cell loss and gliosis are not sufficient to alter the lineage potential of these progenitors in ALS mice. PMID:21092857

  20. Transcriptional analysis of glial cell differentiation in the postnatal murine spinal cord.

    PubMed

    Raddatz, Barbara B; Lehmbecker, Annika; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner

    2015-05-01

    Postnatal murine spinal cord represents a good model system to study mammalian central nervous system myelination in vivo as a basis for further studies in demyelinating diseases. Transcriptional changes were analyzed in SJL/J mice on postnatal day 0, 14, 49 and 231 (P0, P14, P49, P231) employing Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. Additionally, marker gene signatures for astrocyte and oligodendrocyte lineage-stages were defined to study their gene expression in more detail. In addition, immunohistochemistry was used to quantify the abundance of commonly used glial cell markers. 6092 differentially regulated genes (DEGs) were identified. The up-regulated DEGs at P14, P49 and P231 compared to P0 exhibited significantly enriched associations to gene ontology terms such as myelination and lipid metabolic transport and down-regulated DEGs to neurogenesis and axonogenesis. Expression values of marker gene signatures for neural stem cells, oligodendrocyte precursor cells, and developing astrocytes were constantly decreasing, whereas myelinating oligodendrocyte and mature astrocyte markers showed a steady increase. Molecular findings were substantiated by immunohistochemical observations. The transcriptional changes observed are an important reference for future analysis of degenerative and inflammatory conditions in the spinal cord.

  1. NG2 glial cells integrate synaptic input in global and dendritic calcium signals

    PubMed Central

    Sun, Wenjing; Matthews, Elizabeth A; Nicolas, Vicky; Schoch, Susanne; Dietrich, Dirk

    2016-01-01

    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 Ca2+ signals mediated by low-voltage activated Ca2+ channels under strict inhibitory control of voltage-gated A-type K+ channels. Ca2+ signals can be global and originate throughout the cell. However, voltage-gated channels are also found in thin dendrites which act as compartmentalized processing units and generate local calcium transients. Taken together, the activity-dependent control of Ca2+ signals by A-type channels and the global versus local signaling domains make intracellular Ca2+ in NG2 cells a prime signaling molecule to transform neurotransmitter release into activity-dependent myelination. DOI: http://dx.doi.org/10.7554/eLife.16262.001 PMID:27644104

  2. NG2 glial cells integrate synaptic input in global and dendritic calcium signals.

    PubMed

    Sun, Wenjing; Matthews, Elizabeth A; Nicolas, Vicky; Schoch, Susanne; Dietrich, Dirk

    2016-09-19

    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. Ca(2+) signals can be global and originate throughout the cell. However, voltage-gated channels are also found in thin dendrites which act as compartmentalized processing units and generate local calcium transients. Taken together, the activity-dependent control of Ca(2+) signals by A-type channels and the global versus local signaling domains make intracellular Ca(2+) in NG2 cells a prime signaling molecule to transform neurotransmitter release into activity-dependent myelination.

  3. Clear air turbulence forecasting techniques

    NASA Technical Reports Server (NTRS)

    Keller, J. L.

    1980-01-01

    A method to improve clear air turbulence (CAT) forecasting by more effectively using the currently operational rawinsonde (RW) system is discussed. The method is called the Diagnostic Richardson Number Tendency (DRT) technique. The technique does not attempt to use the RW as a direct detector of the turbulent motion or even of the CAT mechanism structure but rather senses the synoptic scale centers of action which provide the energy to the CAT mechanism at the mesoscale level. The DRT algorithm is deterministic rather than statistical in nature, using the hydrodynamic equations (equations of motion) relevant to the synoptic scale. However, interpretation, by necessity, is probabilistic. What is most important with respect to its operational implementation is that this method uses the same input data as currently used by the operational National Meteorological Center prognostic models.

  4. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    SciTech Connect

    Genethliou, Nicholas; Panayiotou, Elena; Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir; Gasperi, Rita De; Elder, Gregory; Kessaris, Nicoletta; Richardson, William D.; Malas, Stavros

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  5. Fine Astrocyte Processes Contain Very Small Mitochondria: Glial Oxidative Capability May Fuel Transmitter Metabolism.

    PubMed

    Derouiche, Amin; Haseleu, Julia; Korf, Horst-Werner

    2015-12-01

    The peripheral astrocyte process (PAP) is the glial compartment largely handling inactivation of transmitter glutamate, and supplying glutamate to the axon terminal. It is not clear how these energy demanding processes are fueled, and whether the PAP exhibits oxidative capability. Whereas the GFAP-positive perinuclear cytoplasm and stem process are rich in mitochondria, the PAP is often considered too narrow to contain mitochondria and might thus not rely on oxidative metabolism. Applying high resolution light microscopy, we investigate here the presence of mitochondria in the PAPs of freshly dissociated, isolated astrocytes. We provide an overview of the subcellular distribution and the approximate size of astrocytic mitochondria. A substantial proportion of the astrocyte's mitochondria are contained in the PAPs and, on the average, they are smaller there than in the stem processes. The majority of mitochondria in the stem and peripheral processes are surprisingly small (0.2-0.4 µm), spherical and not elongate, or tubular, which is supported by electron microscopy. The density of mitochondria is two to several times lower in the PAPs than in the stem processes. Thus, PAPs do not constitute a mitochondria free glial compartment but contain mitochondria in large numbers. No juxtaposition of mitochondria-containing PAPs and glutamatergic synapses has been reported. However, the issue of sufficient ATP concentrations in perisynaptic PAPs can be seen in the light of (1) the rapid, activity dependent PAP motility, and (2) the recently reported activity-dependent mitochondrial transport and immobilization leading to spatial, subcellular organisation of glutamate uptake and oxidative metabolism.

  6. Progressing from identification and functional analysis of precursor behavior to treatment of self-injurious behavior.

    PubMed

    Dracobly, Joseph D; Smith, Richard G

    2012-01-01

    This multiple-study experiment evaluated the utility of assessing and treating severe self-injurious behavior SIB based on the outcomes of a functional analysis of precursor behavior. In Study 1, a precursor to SIB was identified using descriptive assessment and conditional probability analyses. In Study 2, a functional analysis of precursor behavior was conducted. Finally, study 3 evaluated the effects of a treatment in which precursor behavior produced the maintaining variable identified in the precursor functional analysis. Studies 1 and 3 were conducted in two settings in the participants natural environment, where data collection was ongoing throughout the course of the study. Results showed that it was possible to identify a precursor to infrequent but severe SIB, that a functional analysis of precursor behavior suggested a clear operant function, and that treatment based on the results of the precursor functional analysis reduced SIB in the natural environment.

  7. Identified EM Earthquake Precursors

    NASA Astrophysics Data System (ADS)

    Jones, Kenneth, II; Saxton, Patrick

    2014-05-01

    Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After a number of custom rock experiments, two hypotheses were formed which could answer the EM wave model. The first hypothesis concerned a sufficient and continuous electron movement either by surface or penetrative flow, and the second regarded a novel approach to radio transmission. Electron flow along fracture surfaces was determined to be inadequate in creating strong EM fields, because rock has a very high electrical resistance making it a high quality insulator. Penetrative flow could not be corroborated as well, because it was discovered that rock was absorbing and confining electrons to a very thin skin depth. Radio wave transmission and detection worked with every single test administered. This hypothesis was reviewed for propagating, long-wave generation with sufficient amplitude, and the capability of penetrating solid rock. Additionally, fracture spaces, either air or ion-filled, can facilitate this concept from great depths and allow for surficial detection. A few propagating precursor signals have been detected in the field occurring with associated phases using custom-built loop antennae. Field testing was conducted in Southern California from 2006-2011, and outside the NE Texas town of Timpson in February, 2013. The antennae have mobility and observations were noted for

  8. An interstellar precursor mission

    NASA Technical Reports Server (NTRS)

    Jaffe, L. D.; Ivie, C.; Lewis, J. C.; Lipes, R. G.; Norton, H. N.; Stearns, J. W.; Stimpson, L.; Weissman, P.

    1977-01-01

    A mission out of the planetary system, with launch about the year 2000, could provide valuable scientific data as well as test some of the technology for a later mission to another star. Primary scientific objectives for the precursor mission concern characteristics of the heliopause, the interstellar medium, stellar distances (by parallax measurements), low energy cosmic rays, interplanetary gas distribution, and mass of the solar system. Secondary objectives include investigation of Pluto. Candidate science instruments are suggested. Individual spacecraft systems for the mission were considered, technology requirements and problem areas noted, and a number of recommendations made for technology study and advanced development. The most critical technology needs include attainment of 50-yr spacecraft lifetime and development of a long-life NEP system.

  9. Subretinal Glial Membranes in Eyes With Geographic Atrophy

    PubMed Central

    Edwards, Malia M.; McLeod, D. Scott; Bhutto, Imran A.; Grebe, Rhonda; Duffy, Maeve; Lutty, Gerard A.

    2017-01-01

    Purpose Müller cells create the external limiting membrane (ELM) by forming junctions with photoreceptor cells. This study evaluated the relationship between focal photoreceptors and RPE loss in geographic atrophy (GA) and Müller cell extension into the subretinal space. Methods Human donor eyes with no retinal disease or geographic atrophy (GA) were fixed and the eye cups imaged. The retinal posterior pole was stained for glial fibrillary acidic protein (GFAP; astrocytes and activated Müller cells) and vimentin (Müller cells) while the submacular choroids were labeled with Ulex Europaeus Agglutinin lectin (blood vessels). Choroids and retinas were imaged using a Zeiss 710 confocal microscope. Additional eyes were cryopreserved or processed for transmission electron microscopy (TEM) to better visualize the Müller cells. Results Vimentin staining of aged control retinas (n = 4) revealed a panretinal cobblestone-like ELM. While this pattern was also observed in the GA retinas (n = 7), each also had a distinct area in which vimentin+ and vimentin+/GFAP+ processes created a subretinal membrane. Subretinal glial membranes closely matched areas of RPE atrophy in the gross photos. Choroidal vascular loss was also evident in these atrophic areas. Smaller glial projections were noted, which correlated with drusen in gross photos. The presence of glia in the subretinal space was confirmed by TEM and cross cross-section immunohistochemistry. Conclusions In eyes with GA, subretinal Müller cell membranes present in areas of RPE atrophy may be a Müller cell attempt to replace the ELM. These membranes could interfere with treatments such as stem cell therapy. PMID:28249091

  10. Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile.

    PubMed

    Kamendulis, L M; Jiang, J; Xu, Y; Klaunig, J E

    1999-08-01

    Chronic treatment of rats with acrylonitrile (ACN) resulted in a dose-related increase in glial cell tumors (astrocytomas). While the exact mechanism(s) for ACN-induced carcinogenicity remains unresolved, non-genotoxic and possibly tumor promotion modes of action appear to be involved in the induction of glial tumors. Recent studies have shown that ACN induced oxidative stress selectively in rat brain in a dose-responsive manner. The present study examined the ability of ACN to induce oxidative stress in a rat glial cell line, a target tissue, and in cultured rat hepatocytes, a non-target tissue of ACN carcinogenicity. Glial cells and hepatocytes were treated for 1, 4 and 24 h with sublethal concentrations of ACN. ACN induced an increase in oxidative DNA damage, as evidenced by increased production of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in glial cells but not in rat hepatocytes. Hydroxyl radical formation following ACN treatment was also selectively increased in glial cells. Following 1 and 4 h of ACN exposure, the levels of the non-enzymatic antioxidant glutathione, as well as the activities of the enzymatic antioxidants catalase and superoxide dismutase were significantly decreased in the rat glial cells. Lipid peroxidation and the activity of glutathione peroxidase were not affected by ACN treatment in rat glial cells. No changes in any of these biomarkers of oxidative stress were observed in hepatocytes treated with ACN. These data indicate that ACN selectively induced oxidative stress in rat glial cells.

  11. The glial fascicle: an ontogenic and phylogenic unit guiding, supplying and distributing mammalian cortical neurons.

    PubMed

    Gressens, P; Evrard, P

    1993-12-17

    Neurons destined for the mammalian neocortex migrate along radial glial cells (RGCs). This paper describes a comparative study of RGCs in the mouse, rat, hamster, cat and human fetus, selected as representative species of mammalian evolution. The glial fascicles display constant features throughout these species: they consist of 4-10 RGCs filled with glycogen. The glial fascicle guides and probably supplies metabolites to the migrating neurons and organizes the vertical lamination of the developing neocortical plate. The neuronal-glial unit which consists of the RGCs and their affiliated migrating neurons is conserved throughout the species studied, suggesting a designation as a phylogenic unit.

  12. Investigation of terahertz radiation influence on rat glial cells

    PubMed Central

    Borovkova, Mariia; Serebriakova, Maria; Fedorov, Viacheslav; Sedykh, Egor; Vaks, Vladimir; Lichutin, Alexander; Salnikova, Alina; Khodzitsky, Mikhail

    2016-01-01

    We studied an influence of continuous terahertz (THz) radiation (0.12 – 0.18 THz, average power density of 3.2 mW/cm2) on a rat glial cell line. A dose-dependent cytotoxic effect of THz radiation is demonstrated. After 1 minute of THz radiation exposure a relative number of apoptotic cells increased in 1.5 times, after 3 minutes it doubled. This result confirms the concept of biological hazard of intense THz radiation. Diagnostic applications of THz radiation can be restricted by the radiation power density and exposure time. PMID:28101417

  13. Axon-glial interactions at the Drosophila CNS midline.

    PubMed

    Crews, Stephen T

    2010-01-01

    The glia that reside at the midline of the Drosophila CNS are an important embryonic signaling center and also wrap the axons that cross the CNS. The development of the midline glia (MG) is characterized by migration, ensheathment, subdivision of axon commissures, apoptosis, and the extension of glial processes. All of these events are characterized by cell-cell contact between MG and adjacent neurons. Cell adhesion and signaling proteins that mediate different aspects of MG development and MG-neuron interactions have been identified. This provides a foundation for ultimately obtaining an integrated picture of how the MG assemble into a characteristic axonal support structure in the CNS.

  14. Generation of Nonlinear Vortex Precursors

    NASA Astrophysics Data System (ADS)

    Chen, Yue-Yue; Feng, Xun-Li; Liu, Chengpu

    2016-07-01

    We numerically study the propagation of a few-cycle pulse carrying orbital angular momentum (OAM) through a dense atomic system. Nonlinear precursors consisting of high-order vortex harmonics are generated in the transmitted field due to carrier effects associated with ultrafast Bloch oscillation. The nonlinear precursors survive to propagation effects and are well separated with the main pulse, which provides a straightforward way to measure precursors. By virtue of carrying high-order OAM, the obtained vortex precursors as information carriers have potential applications in optical information and communication fields where controllable loss, large information-carrying capacity, and high speed communication are required.

  15. Glial cell plasticity in sensory ganglia induced by nerve damage.

    PubMed

    Hanani, M; Huang, T Y; Cherkas, P S; Ledda, M; Pannese, E

    2002-01-01

    Numerous studies have been done on the effect of nerve injury on neurons of sensory ganglia but little is known about the contribution of satellite glial cells (SCs) in these ganglia to post-injury events. We investigated cell-to-cell coupling and ultrastructure of SCs in mouse dorsal root ganglia after nerve injury (axotomy). Under control conditions SCs were mutually coupled, but mainly to other SCs around a given neuron. After axotomy SCs became extensively coupled to SCs that enveloped other neurons, apparently by gap junctions. Serial section electron microscopy showed that after axotomy SC sheaths enveloping neighboring neurons formed connections with each other. Such connections were absent in control ganglia. The number of gap junctions between SCs increased 6.5-fold after axotomy. We propose that axotomy induces growth of perineuronal SC sheaths, leading to contacts between SCs enveloping adjacent neurons and to formation of new gap junctions between SCs. These changes may be an important mode of glial plasticity and can contribute to neuropathic pain.

  16. Glutamate dehydrogenase 1 and SIRT4 regulate glial development.

    PubMed

    Komlos, Daniel; Mann, Kara D; Zhuo, Yue; Ricupero, Christopher L; Hart, Ronald P; Liu, Alice Y-C; Firestein, Bonnie L

    2013-03-01

    Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by an activation mutation of glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme responsible for the reversible interconversion between glutamate and α-ketoglutarate. The syndrome presents clinically with hyperammonemia, significant episodic hypoglycemia, seizures, and frequent incidences of developmental and learning defects. Clinical research has implicated that although some of the developmental and neurological defects may be attributed to hypoglycemia, some characteristics cannot be ascribed to low glucose and as hyperammonemia is generally mild and asymptomatic, there exists the possibility that altered GDH1 activity within the brain leads to some clinical changes. GDH1 is allosterically regulated by many factors, and has been shown to be inhibited by the ADP-ribosyltransferase sirtuin 4 (SIRT4), a mitochondrially localized sirtuin. Here we show that SIRT4 is localized to mitochondria within the brain. SIRT4 is highly expressed in glial cells, specifically astrocytes, in the postnatal brain and in radial glia during embryogenesis. Furthermore, SIRT4 protein decreases in expression during development. We show that factors known to allosterically regulate GDH1 alter gliogenesis in CTX8 cells, a novel radial glial cell line. We find that SIRT4 and GDH1 overexpression play antagonistic roles in regulating gliogenesis and that a mutant variant of GDH1 found in HI/HA patients accelerates the development of glia from cultured radial glia cells.

  17. Satellite glial cell responses to neuronal firing in the nervous system of Helix pomatia.

    PubMed

    Gommerat, I; Gola, M

    1994-03-01

    Patch clamp experiments were conducted on satellite glial cells attached to the cell body of neurons in place within the nervous system of the snail Helix pomatia. The glial cells were studied using cell-attached and whole-cell patch clamp configurations while the underlying neurons were under current or voltage clamp control. The resting potential of the glial cells (-69 mV) was more negative than that of the underlying neurons (-53 mV), due to their high K+ selectivity. Densely packed K+ channels were present, some of which were active at the cell resting potential. Neuronal firing elicited a cumulative depolarization of the glial cells. Large K+ currents flowing from V-clamped neurons depolarized the glial layer by up to 30 mV. The glial depolarization was directly correlated with the size of the neuronal K+ current. The glial cells recovered their resting potential within 2-5 sec. The neuronal depolarization induced a delayed (20-30 sec) and persistent (3-4 min) increase in the glial K+ channel opening probability. Likewise, pulses of K+ (20-50 mM)-rich saline activated the glial channels, unless the underlying neuron was held hyperpolarized. In low Ca(2+)-high Mg2+ saline, neuron depolarization and K(+)-rich saline did not activate the glial K+ channels. These data indicate that a calcium-dependent signal released from the neuronal cell body was involved in glial channel regulation. Neuron-induced channel opening may help eliminate the K+ ions flowing from active neurons.

  18. A Mathematical Model of Regenerative Axon Growing along Glial Scar after Spinal Cord Injury

    PubMed Central

    Chen, Xuning; Zhu, Weiping

    2016-01-01

    A major factor in the failure of central nervous system (CNS) axon regeneration is the formation of glial scar after the injury of CNS. Glial scar generates a dense barrier which the regenerative axons cannot easily pass through or by. In this paper, a mathematical model was established to explore how the regenerative axons grow along the surface of glial scar or bypass the glial scar. This mathematical model was constructed based on the spinal cord injury (SCI) repair experiments by transplanting Schwann cells as bridge over the glial scar. The Lattice Boltzmann Method (LBM) was used in this model for three-dimensional numerical simulation. The advantage of this model is that it provides a parallel and easily implemented algorithm and has the capability of handling complicated boundaries. Using the simulated data, two significant conclusions were made in this study: (1) the levels of inhibitory factors on the surface of the glial scar are the main factors affecting axon elongation and (2) when the inhibitory factor levels on the surface of the glial scar remain constant, the longitudinal size of the glial scar has greater influence on the average rate of axon growth than the transverse size. These results will provide theoretical guidance and reference for researchers to design efficient experiments. PMID:27274762

  19. Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro

    PubMed Central

    1995-01-01

    The amyloid precursor protein (APP) is a transmembrane protein expressed in several cell types. In the nervous system, APP is expressed by glial and neuronal cells, and several lines of evidence suggest that it plays a role in normal and pathological phenomena. To address the question of the actual function of APP in normal developing neurons, we undertook a study aimed at blocking APP expression using antisense oligonucleotides. Oligonucleotide internalization was achieved by linking them to a vector peptide that translocates through biological membranes. This original technique, which is very efficient and gives direct access to the cell cytosol and nucleus, allowed us to work with extracellular oligonucleotide concentrations between 40 and 200 nM. Internalization of antisense oligonucleotides overlapping the origin of translation resulted in a marked but transient decrease in APP neosynthesis that was not observed with the vector peptide alone, or with sense oligonucleotides. Although transient, the decrease in APP neosynthesis was sufficient to provoke a distinct decrease in axon and dendrite outgrowth by embryonic cortical neurons developing in vitro. The latter decrease was not accompanied by changes in the spreading of the cell bodies. A single exposure to coupled antisense oligonucleotides at the onset of the culture was sufficient to produce significant morphological effects 6, 18, and 24 h later, but by 42 h, there were no remaining significant morphologic changes. This report thus demonstrates that amyloid precursor protein plays an important function in the morphological differentiation of cortical neurons in primary culture. PMID:7876315

  20. Protein misfolding and oxidative stress promote glial-mediated neurodegeneration in an Alexander disease model

    PubMed Central

    Wang, Liqun; Colodner, Kenneth J.; Feany, Mel B.

    2011-01-01

    Although alterations in glial structure and function commonly accompany death of neurons in neurodegenerative diseases, the role glia play in modulating neuronal loss is poorly understood. We have created a model of Alexander disease in Drosophila by expressing disease-linked mutant versions of glial fibrillary acidic protein (GFAP) in fly glia. We find aggregation of mutant human GFAP into inclusions bearing the hallmarks of authentic Rosenthal fibers. We also observe significant toxicity of mutant human GFAP to glia, which is mediated by protein aggregation and oxidative stress. Both protein aggregation and oxidative stress contribute to activation of a robust autophagic response in glia. Toxicity of mutant GFAP to glial cells induces a non-cell autonomous stress response and subsequent apoptosis in neurons, which is dependent on glial glutamate transport. Our findings thus establish a simple genetic model of Alexander disease and further identify cellular pathways critical for glial-induced neurodegeneration. PMID:21414908

  1. Friend or foe? Resolving the impact of glial responses in glaucoma.

    PubMed

    Johnson, Elaine C; Morrison, John C

    2009-01-01

    Glaucomatous vision loss results from the progressive degeneration of optic nerve axons and the death of retinal ganglion cells. This process is accompanied by dramatic alterations in the functional properties and distribution of glial cells in both the retina and the optic nerve head in a reaction commonly referred to as glial activation. The recent availability of rodent and cell culture glaucoma models has substantially contributed to our knowledge of glial activation under glaucomatous conditions. Conclusions drawn from these studies have led to the refinement of existing hypotheses and the generation of new ones. Because these hypotheses encompass both protective and injurious roles for glia, the impact of specific aspects of glial activation are current topics of intensive research, speculation, and debate in the field. With these unresolved issues in mind, this review will summarize recent progress in our understanding of the process of glial activation in the glaucomatous optic nerve head and retina.

  2. Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures.

    PubMed

    Silva, Thayane Martins; França, Guilherme Rapozeiro; Ornelas, Isis Moraes; Loiola, Erick Correia; Ulrich, Henning; Ventura, Ana Lucia Marques

    2015-06-01

    When retinal cell cultures were mechanically scratched, cell growth over the empty area was observed. Only dividing and migrating, 2 M6-positive glial cells were detected. Incubation of cultures with apyrase (APY), suramin, or Reactive Blue 2 (RB-2), but not MRS 2179, significantly attenuated the growth of glial cells, suggesting that nucleotide receptors other than P2Y1 are involved in the growth of glial cells. UTPγS but not ADPβS antagonized apyrase-induced growth inhibition in scratched cultures, suggesting the participation of UTP-sensitive receptors. No decrease in proliferating cell nuclear antigen (PCNA(+)) cells was observed at the border of the scratch in apyrase-treated cultures, suggesting that glial proliferation was not affected. In apyrase-treated cultures, glial cytoplasm protrusions were smaller and unstable. Actin filaments were less organized and alfa-tubulin-labeled microtubules were mainly parallel to scratch. In contrast to control cultures, very few vinculin-labeled adhesion sites could be noticed in these cultures. Increased Akt and ERK phosphorylation was observed in UTP-treated cultures, effect that was inhibited by SRC inhibitor 1 and PI3K blocker LY294002. These inhibitors and the FAK inhibitor PF573228 also decreased glial growth over the scratch, suggesting participation of SRC, PI3K, and FAK in UTP-induced growth of glial cells in scratched cultures. RB-2 decreased dissociated glial cell attachment to fibronectin-coated dishes and migration through transwell membranes, suggesting that nucleotides regulated adhesion and migration of glial cells. In conclusion, mechanical scratch of retinal cell cultures induces growth of glial cells over the empty area through a mechanism that is dependent on activation of UTP-sensitive receptors, SRC, PI3K, and FAK.

  3. Sox2 promotes survival of satellite glial cells in vitro

    SciTech Connect

    Koike, Taro Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  4. Glial Cell Calcium Signaling Mediates Capillary Regulation of Blood Flow in the Retina

    PubMed Central

    Biesecker, Kyle R.; Srienc, Anja I.; Shimoda, Angela M.; Agarwal, Amit; Bergles, Dwight E.; Kofuji, Paulo

    2016-01-01

    The brain is critically dependent on the regulation of blood flow to nourish active neurons. One widely held hypothesis of blood flow regulation holds that active neurons stimulate Ca2+ increases in glial cells, triggering glial release of vasodilating agents. This hypothesis has been challenged, as arteriole dilation can occur in the absence of glial Ca2+ signaling. We address this controversy by imaging glial Ca2+ signaling and vessel dilation in the mouse retina. We find that sensory stimulation results in Ca2+ increases in the glial endfeet contacting capillaries, but not arterioles, and that capillary dilations often follow spontaneous Ca2+ signaling. In IP3R2−/− mice, where glial Ca2+ signaling is reduced, light-evoked capillary, but not arteriole, dilation is abolished. The results show that, independent of arterioles, capillaries actively dilate and regulate blood flow. Furthermore, the results demonstrate that glial Ca2+ signaling regulates capillary but not arteriole blood flow. SIGNIFICANCE STATEMENT We show that a Ca2+-dependent glial cell signaling mechanism is responsible for regulating capillary but not arteriole diameter. This finding resolves a long-standing controversy regarding the role of glial cells in regulating blood flow, demonstrating that glial Ca2+ signaling is both necessary and sufficient to dilate capillaries. While the relative contributions of capillaries and arterioles to blood flow regulation remain unclear, elucidating the mechanisms that regulate capillary blood flow may ultimately lead to the development of therapies for treating diseases where blood flow regulation is disrupted, including Alzheimer's disease, stroke, and diabetic retinopathy. This finding may also aid in revealing the underlying neuronal activity that generates BOLD fMRI signals. PMID:27605617

  5. 17 CFR 22.6 - Futures Commission Merchants and derivatives clearing organizations: Naming of Cleared Swaps...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and derivatives clearing organizations: Naming of Cleared Swaps Customer Accounts. 22.6 Section 22.6... Futures Commission Merchants and derivatives clearing organizations: Naming of Cleared Swaps Customer... derivatives clearing organization maintains with a Permitted Depository shall: (a) Clearly identify...

  6. Gliopathic pain: when satellite glial cells go bad.

    PubMed

    Ohara, Peter T; Vit, Jean-Philippe; Bhargava, Aditi; Romero, Marcela; Sundberg, Christopher; Charles, Andrew C; Jasmin, Luc

    2009-10-01

    Neurons in sensory ganglia are surrounded by satellite glial cells (SGCs) that perform similar functions to the glia found in the CNS. When primary sensory neurons are injured, the surrounding SGCs undergo characteristic changes. There is good evidence that the SGCs are not just bystanders to the injury but play an active role in the initiation and maintenance of neuronal changes that underlie neuropathic pain. In this article the authors review the literature on the relationship between SGCs and nociception and present evidence that changes in SGC potassium ion buffering capacity and glutamate recycling can lead to neuropathic pain-like behavior in animal models. The role that SGCs play in the immune responses to injury is also considered. We propose the term gliopathic pain to describe those conditions in which central or peripheral glia are thought to be the principal generators of principal pain generators.

  7. Neuronal-glial networks as substrate for CNS integration

    PubMed Central

    Verkhratsky, A; Toescu, E C

    2006-01-01

    Astrocytes have been considered, for a long time, as the support and house-keeping cells of the nervous system. Indeed, the astrocytes play very important metabolic roles in the brain, but the catalogue of nervous system functions or activities that involve directly glial participation has extended dramatically in the last decade. In addition to the further refining of the signalling capacity of the neuroglial networks and the detailed reassessment of the interactions between glia and vascular bed in the brain, one of the important salient features of the increased glioscience activity in the last few years was the morphological and functional demonstration that protoplasmic astrocytes occupy well defined spatial territories, with only limited areas of morphological overlapping, but still able to communicate with adjacent neighbours through intercellular junctions. All these features form the basis for a possible reassessment of the nature of integration of activity in the central nervous system that could raise glia to a role of central integrator.

  8. Evidence for brain glial activation in chronic pain patients.

    PubMed

    Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

    2015-03-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions.

  9. Depression as a Glial-Based Synaptic Dysfunction

    PubMed Central

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M.; Gonçalves, Francisco Q.; Real, Joana I.; Prediger, Rui D.; Gonçalves, Nélio; Gomes, Catarina A.; Canas, Paula M.; Agostinho, Paula; Cunha, Rodrigo A.

    2016-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the “quad-partite” synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia “activation” in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain-derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication—such as the purinergic neuromodulation system operated by adenosine 5′-triphosphate (ATP) and adenosine—emerge as promising candidates to “re-normalize” synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future

  10. Glial dysfunction in parkin null mice: effects of aging.

    PubMed

    Solano, Rosa M; Casarejos, Maria J; Menéndez-Cuervo, Jamie; Rodriguez-Navarro, Jose A; García de Yébenes, Justo; Mena, Maria A

    2008-01-16

    Parkin mutations in humans produce parkinsonism whose pathogenesis is related to impaired protein degradation, increased free radicals, and abnormal neurotransmitter release. The role of glia in parkin deficiency is little known. We cultured midbrain glia from wild-type (WT) and parkin knock-out (PK-KO) mice. After 18-20 d in vitro, PK-KO glial cultures had less astrocytes, more microglia, reduced proliferation, and increased proapoptotic protein expression. PK-KO glia had greater levels of intracellular glutathione (GSH), increased mRNA expression of the GSH-synthesizing enzyme gamma-glutamylcysteine synthetase, and greater glutathione S-transferase and lower glutathione peroxidase activities than WT. The reverse happened in glia cultured in serum-free defined medium (EF12) or in old cultures. PK-KO glia was more susceptible than WT to transference to EF12 or neurotoxins (1-methyl-4-phenylpyridinium, blockers of GSH synthesis or catalase, inhibitors of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3 kinases), aging of the culture, or combination of these insults. PK-KO glia was less susceptible than WT to Fe2+ plus H2O2 and less responsive to protection by deferoxamine. Old WT glia increased the expression of heat shock protein 70, but PK-KO did not. Glia conditioned medium (GCM) from PK-KO was less neuroprotective and had lower levels of GSH than WT. GCM from WT increased the levels of dopamine markers in midbrain neuronal cultures transferred to EF12 more efficiently than GCM from PK-KO, and the difference was corrected by supplementation with GSH. PK-KO-GCM was a less powerful suppressor of apoptosis and microglia in neuronal cultures. Our data prove that abnormal glial function is critical in parkin mutations, and its role increases with aging.

  11. Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia.

    PubMed

    Stokes, Jennifer Ann; Arbogast, Tara Elizabeth; Moya, Esteban A; Fu, Zhenxing; Powell, Frank L

    2017-01-18

    Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia, and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg, i.p. daily) or saline beginning one day before and during 7 days of chronic hypoxia (CH, PIO2 = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly (p < 0.001) decreased ventilation during acute hypoxia in CH rats. However, minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 minutes to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 hour of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 hours of CH. Astrocytes increased GFAP antibody immunofluorescent intensity, indicating activation, at both 4 and 24 hours of CH. Minocycline had no effect on glia in normoxia, but significantly decreased microglia activation at 1 hour of CH and astrocyte activation at 24 hours of CH. These results support a role for glial cells providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia.

  12. Glial regulation of extrasynaptic NMDA receptor-mediated excitation of supraoptic nucleus neurones during dehydration.

    PubMed

    Joe, N; Scott, V; Brown, C H

    2014-01-01

    Magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) project to the posterior pituitary gland where they release the hormones, vasopressin and oxytocin into the circulation to maintain plasma osmolality. Hormone release is proportionate to SON MNC action potential (spike) firing rate. When activated by ambient extracellular glutamate, extrasynaptic NMDA receptors (eNMDARs) mediate a tonic (persistent) depolarisation to increase the probability of action potential firing. In the present study, in vivo single-unit electrophysiological recordings were made from urethane-anaesthetised female Sprague-Dawley rats to investigate the impact of tonic eNMDAR activation on MNC activity. Water deprivation (for up to 48 h) caused an increase in the firing rate of SON MNCs that was associated with a general increase in post-spike excitability. To determine whether eNMDAR activation contributes to the increased MNC excitability during water deprivation, memantine, which preferentially blocks eNMDARs, was administered locally into the SON by microdialysis. Memantine significantly decreased the firing rate of MNCs recorded from 48-h water-deprived rats but had no effect on MNCs recorded from euhydrated rats. In the presence of the glial glutamate transporter-1 (GLT-1) blocker, dihydrokainate, memantine also reduced the MNC firing rate in euhydrated rats. Taken together, these observations suggest that GLT-1 clears extracellular glutamate to prevent the activation of eNDMARs under basal conditions and that, during dehydration, eNMDAR activation contributes to the increased firing rate of MNCs.

  13. Preparation of superconductor precursor powders

    DOEpatents

    Bhattacharya, Raghunath

    1998-01-01

    A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic and/or reduced particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of all metals in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

  14. NG2 glial cells regulate neuroimmunological responses to maintain neuronal function and survival

    PubMed Central

    Nakano, Masayuki; Tamura, Yasuhisa; Yamato, Masanori; Kume, Satoshi; Eguchi, Asami; Takata, Kumi; Watanabe, Yasuyoshi; Kataoka, Yosky

    2017-01-01

    NG2-expressing neural progenitor cells (i.e., NG2 glial cells) maintain their proliferative and migratory activities even in the adult mammalian central nervous system (CNS) and produce myelinating oligodendrocytes and astrocytes. Although NG2 glial cells have been observed in close proximity to neuronal cell bodies in order to receive synaptic inputs, substantive non-proliferative roles of NG2 glial cells in the adult CNS remain unclear. In the present study, we generated NG2-HSVtk transgenic rats and selectively ablated NG2 glial cells in the adult CNS. Ablation of NG2 glial cells produced defects in hippocampal neurons due to excessive neuroinflammation via activation of the interleukin-1 beta (IL-1β) pro-inflammatory pathway, resulting in hippocampal atrophy. Furthermore, we revealed that the loss of NG2 glial cell-derived hepatocyte growth factor (HGF) exacerbated these abnormalities. Our findings suggest that NG2 glial cells maintain neuronal function and survival via the control of neuroimmunological function. PMID:28195192

  15. The role of Ca 2+-related signaling in photodynamic injury of nerve and glial cells

    NASA Astrophysics Data System (ADS)

    Lobanov, A. V.; Petin, Y. O.; Uzdensky, A. B.

    2007-05-01

    Photodynamic therapy (PDT) inhibited and irreversibly abolished firing, caused necrosis of neurons, necrosis, apoptosis and proliferation of glial cells in the isolated crayfish stretch receptor. The role in these processes of the central components of Ca 2+-mediated signaling pathway: phospholipase C, calmodulin, calmodulin-dependent kinase II, and protein kinase C was studied using their inhibitors: ET-18, fluphenazine, KN-93, or staurosporine, respectively. ET-18 reduced functional inactivation of neurons, necrosis and apoptosis of glial cells. Fluphenazine and KN-93 reduced PDT-induced necrosis of neurons and glial cells. Staurosporine enhanced PDT-induced glial apoptosis. PDTinduced gliosis was prevented by KN-93 and staurosporine. Therefore, phospholipase C participated in neuron inactivation and glial necrosis and apoptosis. Calmodulin and calmodulin-dependent kinase II were involved in PDT-induced necrosis of neurons and glial cells but not in glial apoptosis. Protein kinase C protected glia from apoptosis and participated in PDT-induced gliosis and loss of neuronal activity. These data may be used for modulation of PDT of brain tumors.

  16. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2011-03-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  17. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2010-10-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  18. Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility

    PubMed Central

    Melom, Jan E.; Littleton, J. Troy

    2013-01-01

    Glia exhibit spontaneous and activity-dependent fluctuations in intracellular Ca2+, yet it is unclear whether glial Ca2+ oscillations are required during neuronal signaling. Somatic glial Ca2+ waves are primarily mediated by the release of intracellular Ca2+ stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca2+ transients were identified in fine astrocytic processes and found to arise via an intracellular store-independent process. Here, we describe the identification of rapid, near-membrane Ca2+ oscillations in Drosophila cortex glia of the CNS. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na+/Ca2+, K+ exchanger (zydeco) that is required for microdomain Ca2+ oscillatory activity. We found that zydeco mutant animals exhibit increased susceptibility to seizures in response to a variety of environmental stimuli, and that zydeco is required acutely in cortex glia to regulate seizure susceptibility. We also found that glial expression of calmodulin is required for stress-induced seizures in zydeco mutants, suggesting a Ca2+/calmodulin-dependent glial signaling pathway underlies glial–neuronal communication. These studies demonstrate that microdomain glial Ca2+ oscillations require NCKX-mediated plasma membrane Ca2+ flux, and that acute dysregulation of glial Ca2+ signaling triggers seizures. PMID:23325253

  19. The glial investment of the adult and developing antennal lobe of Drosophila

    PubMed Central

    Oland, Lynne A.; Biebelhausen, John P.; Tolbert, Leslie P.

    2009-01-01

    In recent years, the Drosophila olfactory system, with its unparalleled opportunities for genetic dissection of development and functional organization, has been used to study the development of central olfactory neurons and the molecular basis of olfactory coding. The results of these studies have been interpreted in the absence of a detailed understanding of the steps in maturation of glial cells in the antennal lobe. Here, we present a high-resolution study of the glia associated with olfactory glomeruli in adult and developing antennal lobes. The study provides a basis for comparison of findings in Drosophila with those in the moth Manduca sexta that indicate a critical role for glia in antennal lobe development. Using flies expressing GFP under a Nervana2 driver to visualize glia for confocal microscopy, and probing at higher resolution with the electron microscope, we find that glial development in Drosophila differs markedly from that in moths: glial cell bodies remain in a rind around the glomerular neuropil; glial processes ensheathe axon bundles in the nerve layer but likely contribute little to axonal sorting; their processes insinuate between glomeruli only very late and then form only a sparse, open network around each glomerulus; and glial processes invade the synaptic neuropil. Taking our results in the context of previous studies, we conclude that glial cells in the developing Drosophila antennal lobe are unlikely to play a strong role in either axonal sorting or glomerulus stabilization and that in the adult, glial processes do not electrically isolate glomeruli from their neighbors. PMID:18537134

  20. Radial glial cells play a key role in echinoderm neural regeneration

    PubMed Central

    2013-01-01

    Background Unlike the mammalian central nervous system (CNS), the CNS of echinoderms is capable of fast and efficient regeneration following injury and constitutes one of the most promising model systems that can provide important insights into evolution of the cellular and molecular events involved in neural repair in deuterostomes. So far, the cellular mechanisms of neural regeneration in echinoderm remained obscure. In this study we show that radial glial cells are the main source of new cells in the regenerating radial nerve cord in these animals. Results We demonstrate that radial glial cells of the sea cucumber Holothuria glaberrima react to injury by dedifferentiation. Both glia and neurons undergo programmed cell death in the lesioned CNS, but it is the dedifferentiated glial subpopulation in the vicinity of the injury that accounts for the vast majority of cell divisions. Glial outgrowth leads to formation of a tubular scaffold at the growing tip, which is later populated by neural elements. Most importantly, radial glial cells themselves give rise to new neurons. At least some of the newly produced neurons survive for more than 4 months and express neuronal markers typical of the mature echinoderm CNS. Conclusions A hypothesis is formulated that CNS regeneration via activation of radial glial cells may represent a common capacity of the Deuterostomia, which is not invoked spontaneously in higher vertebrates, whose adult CNS does not retain radial glial cells. Potential implications for biomedical research aimed at finding the cure for human CNS injuries are discussed. PMID:23597108

  1. The Drosophila blood-brain barrier: development and function of a glial endothelium

    PubMed Central

    Limmer, Stefanie; Weiler, Astrid; Volkenhoff, Anne; Babatz, Felix; Klämbt, Christian

    2014-01-01

    The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial (SPG) cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells. PMID:25452710

  2. Photodynamic therapy-induced nitric oxide production in neuronal and glial cells

    NASA Astrophysics Data System (ADS)

    Kovaleva, Vera D.; Uzdensky, Anatoly B.

    2016-10-01

    Nitric oxide (NO) has been recently demonstrated to enhance apoptosis of glial cells induced by photodynamic therapy (PDT), but to protect glial cells from PDT-induced necrosis in the crayfish stretch receptor, a simple neuroglial preparation that consists of a single mechanosensory neuron enveloped by satellite glial cells. We used the NO-sensitive fluorescent probe 4,5-diaminofluorescein diacetate to study the distribution and dynamics of PDT-induced NO production in the mechanosensory neuron and surrounding glial cells. The NO production in the glial envelope was higher than in the neuronal soma axon and dendrites both in control and in experimental conditions. In dark NO generator, DEA NONOate or NO synthase substrate L-arginine hydrochloride significantly increased the NO level in glial cells, whereas NO scavenger 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) or inhibitors of NO synthase L-NG-nitro arginine methyl ester and Nω-nitro-L-arginine decreased it. PDT induced the transient increase in NO production with a maximum at 4 to 7 min after the irradiation start followed by its inhibition at 10 to 40 min. We suggested that PDT stimulated neuronal rather than inducible NO synthase isoform in glial cells, and the produced NO could mediate PDT-induced apoptosis.

  3. Long-Term Maintenance of Na+ Channels at Nodes of Ranvier Depends on Glial Contact Mediated by Gliomedin and NrCAM

    PubMed Central

    Amor, Veronique; Feinberg, Konstantin; Eshed-Eisenbach, Yael; Vainshtein, Anya; Frechter, Shahar; Grumet, Martin; Rosenbluth, Jack

    2014-01-01

    Clustering of Na+ channels at the nodes of Ranvier is coordinated by myelinating glia. In the peripheral nervous system, axoglial contact at the nodes is mediated by the binding of gliomedin and glial NrCAM to axonal neurofascin 186 (NF186). This interaction is crucial for the initial clustering of Na+ channels at heminodes. As a result, it is not clear whether continued axon-glial contact at nodes of Ranvier is required to maintain these channels at the nodal axolemma. Here, we report that, in contrast to mice that lack either gliomedin or NrCAM, absence of both molecules (and hence the glial clustering signal) resulted in a gradual loss of Na+ channels and other axonal components from the nodes, the formation of binary nodes, and dysregulation of nodal gap length. Therefore, these mice exhibit neurological abnormalities and slower nerve conduction. Disintegration of the nodes occurred in an orderly manner, starting with the disappearance of neurofascin 186, followed by the loss of Na+ channels and ankyrin G, and then βIV spectrin, a sequence that reflects the assembly of nodes during development. Finally, the absence of gliomedin and NrCAM led to the invasion of the outermost layer of the Schwann cell membrane beyond the nodal area and the formation of paranodal-like junctions at the nodal gap. Our results reveal that axon-glial contact mediated by gliomedin, NrCAM, and NF186 not only plays a role in Na+ channel clustering during development, but also contributes to the long-term maintenance of Na+ channels at nodes of Ranvier. PMID:24719088

  4. Long-term maintenance of Na+ channels at nodes of Ranvier depends on glial contact mediated by gliomedin and NrCAM.

    PubMed

    Amor, Veronique; Feinberg, Konstantin; Eshed-Eisenbach, Yael; Vainshtein, Anya; Frechter, Shahar; Grumet, Martin; Rosenbluth, Jack; Peles, Elior

    2014-04-09

    Clustering of Na(+) channels at the nodes of Ranvier is coordinated by myelinating glia. In the peripheral nervous system, axoglial contact at the nodes is mediated by the binding of gliomedin and glial NrCAM to axonal neurofascin 186 (NF186). This interaction is crucial for the initial clustering of Na(+) channels at heminodes. As a result, it is not clear whether continued axon-glial contact at nodes of Ranvier is required to maintain these channels at the nodal axolemma. Here, we report that, in contrast to mice that lack either gliomedin or NrCAM, absence of both molecules (and hence the glial clustering signal) resulted in a gradual loss of Na(+) channels and other axonal components from the nodes, the formation of binary nodes, and dysregulation of nodal gap length. Therefore, these mice exhibit neurological abnormalities and slower nerve conduction. Disintegration of the nodes occurred in an orderly manner, starting with the disappearance of neurofascin 186, followed by the loss of Na(+) channels and ankyrin G, and then βIV spectrin, a sequence that reflects the assembly of nodes during development. Finally, the absence of gliomedin and NrCAM led to the invasion of the outermost layer of the Schwann cell membrane beyond the nodal area and the formation of paranodal-like junctions at the nodal gap. Our results reveal that axon-glial contact mediated by gliomedin, NrCAM, and NF186 not only plays a role in Na(+) channel clustering during development, but also contributes to the long-term maintenance of Na(+) channels at nodes of Ranvier.

  5. DOPAL is Transmissible to and Oligomerizes Alpha-Synuclein in Human Glial Cells

    PubMed Central

    Jinsmaa, Yunden; Sullivan, Patricia; Sharabi, Yehonatan; Goldstein, David S.

    2016-01-01

    Introduction Glial cytoplasmic inclusions (GCIs) containing alpha-synuclein (AS) are a neuropathologic hallmark of multiple system atrophy (MSA). Oligomerized AS is thought to be the pathogenic form of the protein. Glial cells normally express little AS, but they can take up AS from the extracellular fluid. 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediate in the intra-neuronal metabolism of dopamine (DA), potently oligomerizes AS. In this study we tested whether DOPAL is taken up by human glial cells and augments intracellular oligomerization of AS. Methods DOPAL (exogenous or endogenous from co-incubation with PC12 cells) and AS (native or A53T mutant form) were added to the incubation medium of glial cells (glioblastoma or MO3.13 oligodendrocytes). Glial cellular contents of DOPAL and its intracellular metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured at up to 180 minutes of incubation. Glial cellular AS oligomers were quantified by Western blotting. Results Neither glioblastoma nor MO3.13 cells contained endogenous catecholamines or AS. Co-incubation of the cells with DA-producing PC12 cells produced time-related increases in DOPAL and DOPAC contents. Similarly, glial cellular DOPAL and DOPAC contents increased rapidly after addition of DOPAL to the medium. After addition of native or A53T-AS, intracellular AS also increased. Incubation of glial cells with both DOPAL and AS enhanced the intracellular oligomerization of native and A53T-AS. Conclusions DOPAL is transmissible to glial cells and enhances intracellular oligomerization of AS. An interaction of DOPAL with AS might help explain the formation of CGIs in MSA. PMID:26777075

  6. Recent progress in tissue optical clearing

    PubMed Central

    Zhu, Dan; Larin, Kirill V; Luo, Qingming; Tuchin, Valery V

    2013-01-01

    Tissue optical clearing technique provides a prospective solution for the application of advanced optical methods in life sciences. This paper gives a review of recent developments in tissue optical clearing techniques. The physical, molecular and physiological mechanisms of tissue optical clearing are overviewed and discussed. Various methods for enhancing penetration of optical-clearing agents into tissue, such as physical methods, chemical-penetration enhancers and combination of physical and chemical methods are introduced. Combining the tissue optical clearing technique with advanced microscopy image or labeling technique, applications for 3D microstructure of whole tissues such as brain and central nervous system with unprecedented resolution are demonstrated. Moreover, the difference in diffusion and/or clearing ability of selected agents in healthy versus pathological tissues can provide a highly sensitive indicator of the tissue health/pathology condition. Finally, recent advances in optical clearing of soft or hard tissue for in vivo imaging and phototherapy are introduced. PMID:24348874

  7. Recent progress in tissue optical clearing.

    PubMed

    Zhu, Dan; Larin, Kirill V; Luo, Qingming; Tuchin, Valery V

    2013-09-01

    Tissue optical clearing technique provides a prospective solution for the application of advanced optical methods in life sciences. This paper gives a review of recent developments in tissue optical clearing techniques. The physical, molecular and physiological mechanisms of tissue optical clearing are overviewed and discussed. Various methods for enhancing penetration of optical-clearing agents into tissue, such as physical methods, chemical-penetration enhancers and combination of physical and chemical methods are introduced. Combining the tissue optical clearing technique with advanced microscopy image or labeling technique, applications for 3D microstructure of whole tissues such as brain and central nervous system with unprecedented resolution are demonstrated. Moreover, the difference in diffusion and/or clearing ability of selected agents in healthy versus pathological tissues can provide a highly sensitive indicator of the tissue health/pathology condition. Finally, recent advances in optical clearing of soft or hard tissue for in vivo imaging and phototherapy are introduced. [Formula: see text].

  8. Matrix metalloproteinase-9 expression in the nuclear compartment of neurons and glial cells in aging and stroke.

    PubMed

    Pirici, Daniel; Pirici, Ionica; Mogoanta, Laurentiu; Margaritescu, Otilia; Tudorica, Valerica; Margaritescu, Claudiu; Ion, Daniela A; Simionescu, Cristiana; Coconu, Marieta

    2012-10-01

    Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology.

  9. 17 CFR 22.3 - Derivatives clearing organizations: Treatment of cleared swaps customer collateral.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Derivatives clearing... Exchanges COMMODITY FUTURES TRADING COMMISSION CLEARED SWAPS § 22.3 Derivatives clearing organizations: Treatment of cleared swaps customer collateral. (a) General. A derivatives clearing organization shall...

  10. 17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... derivatives clearing organization rules and clearing new products. 39.4 Section 39.4 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES CLEARING ORGANIZATIONS § 39.4 Procedures for implementing derivatives clearing organization rules and clearing new products. (a) Request for approval...

  11. 17 CFR 22.3 - Derivatives clearing organizations: Treatment of cleared swaps customer collateral.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Derivatives clearing... Exchanges COMMODITY FUTURES TRADING COMMISSION CLEARED SWAPS § 22.3 Derivatives clearing organizations: Treatment of cleared swaps customer collateral. (a) General. A derivatives clearing organization shall...

  12. 17 CFR 22.3 - Derivatives clearing organizations: Treatment of Cleared Swaps Customer Collateral.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Derivatives clearing... Exchanges COMMODITY FUTURES TRADING COMMISSION CLEARED SWAPS (Eff. 4-9-2012) § 22.3 Derivatives clearing organizations: Treatment of Cleared Swaps Customer Collateral. (a) General. A derivatives clearing...

  13. [Fine structure of glial cells in the central nervous system of the tapeworm Grillotia erinaceus (Cestoda: Trypanorhyncha)].

    PubMed

    Biserova, N M

    2008-01-01

    The problem of glial cells existing in parasitic and free living flatworms is correlated with organization of parenchyma in platyhelmintes. In the contrary to the widespread opinion that myelin-like envelopes and glial cells do not exist in the nervous system of parasitic flatworms, it has been shown by ultrastructural researches that Amphilina foliacea (Cestoda, Amphilinidea) has well developed glial cells and myelin-like envelopes in the ganglia and main cords, which include both glial cells and intercellular components. The aim of our research was to reveal and investigate in details structural components corresponding to the concept of the glial cell in the CNS of Grillotia erinaceus (Cestoda: Trypanorhyncha). Three types of glial cells have been found. The first type is the fibroblast-like glial cells; cells locate in the cerebral ganglion, contain in cytoplasm and extract out fibrillar matrix, form desmosomes and have supporting function. The glial cells of the second type form myeline-like envelope of the giant axons and bulbar nerves in scolex and have laminar cytoplasm. These cells are numerous and exceed in number the neurons bodies into the nerve. The glial cells of the third type form multilayer envelopes in the main nerve cords; extra cellular fibers and gap-junctions take place between the layers. There are contacts between the glial cells of the third type and excretory epithelium but specialized contacts with neurons have been not found. The existing of glial cells in free living and parasitic flatworms is discussed.

  14. Production and perception of clear speech

    NASA Astrophysics Data System (ADS)

    Bradlow, Ann R.

    2003-04-01

    When a talker believes that the listener is likely to have speech perception difficulties due to a hearing loss, background noise, or a different native language, she or he will typically adopt a clear speaking style. Previous research has established that, with a simple set of instructions to the talker, ``clear speech'' can be produced by most talkers under laboratory recording conditions. Furthermore, there is reliable evidence that adult listeners with either impaired or normal hearing typically find clear speech more intelligible than conversational speech. Since clear speech production involves listener-oriented articulatory adjustments, a careful examination of the acoustic-phonetic and perceptual consequences of the conversational-to-clear speech transformation can serve as an effective window into talker- and listener-related forces in speech communication. Furthermore, clear speech research has considerable potential for the development of speech enhancement techniques. After reviewing previous and current work on the acoustic properties of clear versus conversational speech, this talk will present recent data from a cross-linguistic study of vowel production in clear speech and a cross-population study of clear speech perception. Findings from these studies contribute to an evolving view of clear speech production and perception as reflecting both universal, auditory and language-specific, phonological contrast enhancement features.

  15. 17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... so approved. (b) Self-certification of rules. Proposed new or amended rules of a derivatives clearing...) Acceptance of new products for clearing. (1) A dormant derivatives clearing organization within the...

  16. 17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... so approved. (b) Self-certification of rules. Proposed new or amended rules of a derivatives clearing...) Acceptance of new products for clearing. (1) A dormant derivatives clearing organization within the...

  17. Glutathione-Induced Calcium Shifts in Chick Retinal Glial Cells

    PubMed Central

    Freitas, Hercules R.; Ferraz, Gabriel; Ferreira, Gustavo C.; Ribeiro-Resende, Victor T.; Chiarini, Luciana B.; do Nascimento, José Luiz M.; Matos Oliveira, Karen Renata H.; Pereira, Tiago de Lima; Ferreira, Leonardo G. B.; Kubrusly, Regina C.; Faria, Robson X.

    2016-01-01

    Neuroglia interactions are essential for the nervous system and in the retina Müller cells interact with most of the neurons in a symbiotic manner. Glutathione (GSH) is a low-molecular weight compound that undertakes major antioxidant roles in neurons and glia, however, whether this compound could act as a signaling molecule in neurons and/or glia is currently unknown. Here we used embryonic avian retina to obtain mixed retinal cells or purified Müller glia cells in culture to evaluate calcium shifts induced by GSH. A dose response curve (0.1–10mM) showed that 5–10mM GSH, induced calcium shifts exclusively in glial cells (later labeled and identified as 2M6 positive cells), while neurons responded to 50mM KCl (labeled as βIII tubulin positive cells). BBG 100nM, a P2X7 blocker, inhibited the effects of GSH on Müller glia. However, addition of DNQX 70μM and MK-801 20μM, non-NMDA and NMDA blockers, had no effect on GSH calcium induced shift. Oxidized glutathione (GSSG) at 5mM failed to induce calcium mobilization in glia cells, indicating that the antioxidant and/or structural features of GSH are essential to promote elevations in cytoplasmic calcium levels. Indeed, a short GSH pulse (60s) protects Müller glia from oxidative damage after 30 min of incubation with 0.1% H2O2. Finally, GSH induced GABA release from chick embryonic retina, mixed neuron-glia or from Müller cell cultures, which were inhibited by BBG or in the absence of sodium. GSH also induced propidium iodide uptake in Müller cells in culture in a P2X7 receptor dependent manner. Our data suggest that GSH, in addition to antioxidant effects, could act signaling calcium shifts at the millimolar range particularly in Müller glia, and could regulate the release of GABA, with additional protective effects on retinal neuron-glial circuit. PMID:27078878

  18. Magnesium Elevation Promotes Neuronal Differentiation While Suppressing Glial Differentiation of Primary Cultured Adult Mouse Neural Progenitor Cells through ERK/CREB Activation

    PubMed Central

    Liao, Wang; Jiang, Mujun; Li, Mei; Jin, Congli; Xiao, Songhua; Fan, Shengnuo; Fang, Wenli; Zheng, Yuqiu; Liu, Jun

    2017-01-01

    This study aimed to explore the influence of magnesium elevation on fate determination of adult neural progenitor cells (aNPCs) and the underlying mechanism in vitro. Adult neurogenesis, which is the generation of functional neurons from neural precursors, occurs throughout life in restricted anatomical regions in mammals. Magnesium is the fourth most abundant ion in mammals, and its elevation in the brain has been shown to enhance memory and synaptic plasticity in vivo. However, the effects of magnesium on fate determination of aNPCs, which are vital processes in neurogenesis, remain unknown. NPCs isolated from the dentate gyrus of adult C57/BL6 mice were induced to differentiate in a medium with varying magnesium concentrations (0.6, 0.8, and 1.0 mM) and extracellular signal-regulated kinase (ERK) inhibitor PD0325901. The proportion of cells that differentiated into neurons and glial cells was evaluated using immunofluorescence. Quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of β-III tubulin (Tuj1) and glial fibrillary acidic protein (GFAP). The activation of ERK and cAMP response element-binding protein (CREB) was examined by Western blot to reveal the underlying mechanism. Magnesium elevation increased the proportion of Tju1-positive cells and decreased the proportion of GFAP-positive cells. Also, the expression of Tuj1 was upregulated, whereas the expression of GFAP was downregulated. Moreover, magnesium elevation enhanced the activation of both ERK and CREB. Treatment with PD0325901 reversed these effects in a dose-dependent manner. Magnesium elevation promoted neural differentiation while suppressing glial cell differentiation, possibly via ERK-induced CREB activation. PMID:28280456

  19. Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice

    PubMed Central

    Heneka, Michael T; Sastre, Magdalena; Dumitrescu-Ozimek, Lucia; Dewachter, Ilse; Walter, Jochen; Klockgether, Thomas; Van Leuven, Fred

    2005-01-01

    Background Inflammation is suspected to contribute to the progression and severity of neurodegeneration in Alzheimer's disease (AD). Transgenic mice overexpressing the london mutant of amyloid precursor protein, APP [V717I], robustly recapitulate the amyloid pathology of AD. Methods Early and late, temporal and spatial characteristics of inflammation were studied in APP [V717I] mice at 3 and 16 month of age. Glial activation and expression of inflammatory markers were determined by immunohistochemistry and RT-PCR. Amyloid deposition was assessed by immunohistochemistry, thioflavine S staining and western blot experiments. BACE1 activity was detected in brain lysates and in situ using the BACE1 activity kit from R&D Systems, Wiesbaden, Germany. Results Foci of activated micro- and astroglia were already detected at age 3 months, before any amyloid deposition. Inflammation parameters comprised increased mRNA levels coding for interleukin-1β, interleukin-6, major histocompatibility complex II and macrophage-colony-stimulating-factor-receptor. Foci of CD11b-positive microglia expressed these cytokines and were neighbored by activated astrocytes. Remarkably, β-secretase (BACE1) mRNA, neuronal BACE1 protein at sites of focal inflammation and total BACE1 enzyme activity were increased in 3 month old APP transgenic mice, relative to age-matched non-transgenic mice. In aged APP transgenic mice, the mRNA of all inflammatory markers analysed was increased, accompanied by astroglial iNOS expression and NO-dependent peroxynitrite release, and with glial activation near almost all diffuse and senile Aβ deposits. Conclusion The early and focal glial activation, in conjunction with upregulated BACE1 mRNA, protein and activity in the presence of its substrate APP, is proposed to represent the earliest sites of amyloid deposition, likely evolving into amyloid plaques. PMID:16212664

  20. MIO-M1 cells and similar muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics.

    PubMed

    Lawrence, Jean M; Singhal, Shweta; Bhatia, Bhairavi; Keegan, David J; Reh, Thomas A; Luthert, Philip J; Khaw, Peng T; Limb, Gloria Astrid

    2007-08-01

    Growing evidence suggests that glial cells may have a role as neural precursors in the adult central nervous system. Although it has been shown that Müller cells exhibit progenitor characteristics in the postnatal chick and rat retinae, their progenitor-like role in developed human retina is unknown. We first reported the Müller glial characteristics of the spontaneously immortalized human cell line MIO-M1, but recently we have derived similar cell lines from the neural retina of several adult eye donors. Since immortalization is one of the main properties of stem cells, we investigated whether these cells expressed stem cell markers. Cells were grown as adherent monolayers, responded to epidermal growth factor, and could be expanded indefinitely without growth factors under normal culture conditions. They could be frozen and thawed without losing their characteristics. In the presence of extracellular matrix and fibroblast growth factor-2 or retinoic acid, they acquired neural morphology, formed neurospheres, and expressed neural stem cell markers including betaIII tubulin, Sox2, Pax6, Chx10, and Notch 1. They also expressed markers of postmitotic retinal neurons, including peripherin, recoverin, calretinin, S-opsin, and Brn3. When grafted into the subretinal space of dystrophic Royal College of Surgeons rats or neonatal Lister hooded rats, immortalized cells migrated into the retina, where they expressed various markers of retinal neurons. These observations indicate that adult human neural retina harbors a population of cells that express both Müller glial and stem cell markers and suggest that these cells may have potential use for cell-based therapies to restore retinal function. Disclosure of potential conflicts of interest is found at the end of this article.

  1. Major Land Clearing Fires, Kalimantan, Borneo, Indonesia

    NASA Technical Reports Server (NTRS)

    1991-01-01

    These many and intense land clearing fires in the Kalimantan region of the island of Borneo, Indonesia (3.5S, 113.5E) are indicative of the many deforestation activities on a worldwide scale. In order to feed and house ever increasing populations, more cleared land is required for agriculture to feed ever increasing populations. More pasture lands are needed for livestock. And, more cleared lands are needed for housing.

  2. Modulating the Delicate Glial-Neuronal Interactions in Neuropathic Pain: Promises and Potential Caveats

    PubMed Central

    Tiwari, Vinod; Guan, Yun; Raja, Srinivasa N.

    2014-01-01

    During neuropathic pain, glial cells (mainly astrocytes and microglia) become activated and initiate a series of signaling cascades that modulate pain processing at both spinal and supraspinal levels. It has been generally accepted that glial cell activation contributes to neuropathic pain because glia release proinflammatory cytokines, chemokines, and factors such as calcitonin gene-related peptide, substance P, and glutamate, which are known to facilitate pain signaling. However, recent research has shown that activation of glia also leads to some beneficial outcomes. Glia release anti-inflammatory factors that protect against neurotoxicity and restore normal pain. Accordingly, use of glial inhibitors might compromise the protective functions of glia in addition to suppressing their detrimental effects. With a better understanding of how different conditions affect glial cell activation, we may be able to promote the protective function of glia and pave the way for future development of novel, safe, and effective treatments of neuropathic pain. PMID:24820245

  3. An electrically resistive sheet of glial cells for amplifying signals of neuronal extracellular recordings.

    PubMed

    Matsumura, R; Yamamoto, H; Niwano, M; Hirano-Iwata, A

    2016-01-11

    Electrical signals of neuronal cells can be recorded non-invasively and with a high degree of temporal resolution using multielectrode arrays (MEAs). However, signals that are recorded with these devices are small, usually 0.01%-0.1% of intracellular recordings. Here, we show that the amplitude of neuronal signals recorded with MEA devices can be amplified by covering neuronal networks with an electrically resistive sheet. The resistive sheet used in this study is a monolayer of glial cells, supportive cells in the brain. The glial cells were grown on a collagen-gel film that is permeable to oxygen and other nutrients. The impedance of the glial sheet was measured by electrochemical impedance spectroscopy, and equivalent circuit simulations were performed to theoretically investigate the effect of covering the neurons with such a resistive sheet. Finally, the effect of the resistive glial sheet was confirmed experimentally, showing a 6-fold increase in neuronal signals. This technique feasibly amplifies signals of MEA recordings.

  4. A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue

    PubMed Central

    Elsayed, Maha; Magistretti, Pierre J.

    2015-01-01

    Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment. PMID:26733803

  5. Embryonic development of glial cells and myelin in the shark, Chiloscyllium punctatum

    PubMed Central

    Rotenstein, Lisa; Milanes, Anthony; Juarez, Marilyn; Reyes, Michelle; de Bellard, Maria Elena

    2009-01-01

    Glial cells are responsible for a wide range of functions in the nervous system of vertebrates. The myelinated nervous systems of extant elasmobranchs have the longest independent history of all gnathostomes. Much is known about the development of glia in other jawed vertebrates, but research in elasmobranchs is just beginning to reveal the mechanisms guiding neurodevelopment. This study examines the development of glial cells in the bamboo shark, Chiloscyllium punctatum, by identifying the expression pattern of several classic glial and myelin proteins. We show for the first time that glial development in the bamboo shark (Ch. punctamum) embryo follows closely the one observed in other vertebrates and that neural development seems to proceed at a faster rate in the PNS than in the CNS. In addition, we observed more myelinated tracts in the PNS than in the CNS, and as early as stage 32, suggesting that the ontogeny of myelin in sharks is closer to osteichthyans than agnathans. PMID:19733690

  6. An electrically resistive sheet of glial cells for amplifying signals of neuronal extracellular recordings

    NASA Astrophysics Data System (ADS)

    Matsumura, R.; Yamamoto, H.; Niwano, M.; Hirano-Iwata, A.

    2016-01-01

    Electrical signals of neuronal cells can be recorded non-invasively and with a high degree of temporal resolution using multielectrode arrays (MEAs). However, signals that are recorded with these devices are small, usually 0.01%-0.1% of intracellular recordings. Here, we show that the amplitude of neuronal signals recorded with MEA devices can be amplified by covering neuronal networks with an electrically resistive sheet. The resistive sheet used in this study is a monolayer of glial cells, supportive cells in the brain. The glial cells were grown on a collagen-gel film that is permeable to oxygen and other nutrients. The impedance of the glial sheet was measured by electrochemical impedance spectroscopy, and equivalent circuit simulations were performed to theoretically investigate the effect of covering the neurons with such a resistive sheet. Finally, the effect of the resistive glial sheet was confirmed experimentally, showing a 6-fold increase in neuronal signals. This technique feasibly amplifies signals of MEA recordings.

  7. Inflammation after Ischemic Stroke: The Role of Leukocytes and Glial Cells

    PubMed Central

    Kim, Jong Youl; Park, Joohyun; Chang, Ji Young; Kim, Sa-Hyun

    2016-01-01

    The immune response after stroke is known to play a major role in ischemic brain pathobiology. The inflammatory signals released by immune mediators activated by brain injury sets off a complex series of biochemical and molecular events which have been increasingly recognized as a key contributor to neuronal cell death. The primary immune mediators involved are glial cells and infiltrating leukocytes, including neutrophils, monocytes and lymphocyte. After ischemic stroke, activation of glial cells and subsequent release of pro- and anti-inflammatory signals are important for modulating both neuronal cell damage and wound healing. Infiltrated leukocytes release inflammatory mediators into the site of the lesion, thereby exacerbating brain injury. This review describes how the roles of glial cells and circulating leukocytes are a double-edged sword for neuroinflammation by focusing on their detrimental and protective effects in ischemic stroke. Here, we will focus on underlying characterize of glial cells and leukocytes under inflammation after ischemic stroke. PMID:27790058

  8. Precursor decay in several aluminas

    NASA Astrophysics Data System (ADS)

    Murray, N. H.; Bourne, N. K.; Rosenberg, Z.

    1996-05-01

    Plate impact experiments were performed on three ceramics with alumina content varying from 88 to 99.9% using a 50 mm single stage gas gun. Tiles of ceramic with thicknesses varying from 2 to 12 mm were impacted above their Hugoniot Elastic Limits (HELs) and the rate dependent strength was investigated by monitoring the variation in amplitude of the elastic precursor with propagation distance. Stress levels in the target were recorded using manganin stress transducers and a 1 GS s-1 storage oscilloscope. All grades of alumina were found to exhibit some elastic precursor decay indicating strain rate sensitivity.

  9. Implications of glial nitric oxide in neurodegenerative diseases

    PubMed Central

    Yuste, Jose Enrique; Tarragon, Ernesto; Campuzano, Carmen María; Ros-Bernal, Francisco

    2015-01-01

    Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases. PMID:26347610

  10. Glial Reactivity in Resistance to Methamphetamine-Induced Neurotoxicity

    PubMed Central

    Friend, Danielle M.; Keefe, Kristen A.

    2013-01-01

    Neurotoxic regimens of methamphetamine (METH) result in reactive microglia and astrocytes in striatum. Prior data indicate that rats with partial dopamine (DA) loss resulting from prior exposure to METH are resistant to further decreases in striatal DA when re-exposed to METH 30 days later. Such resistant animals also do not show an activated microglia phenotype, suggesting a relation between microglial activation and METH-induced neurotoxicity. To date, the astrocyte response in such resistance has not been examined. Thus, this study examined glial-fibrillary acidic protein (GFAP) and CD11b protein expression in striata of animals administered saline or a neurotoxic regimen of METH on postnatal days 60 and/or 90 (Saline:Saline, Saline:METH, METH:Saline, METH:METH). Consistent with previous work, animals experiencing acute toxicity (Saline:METH) showed both activated microglia and astocytes, whereas those resistant to the acute toxicity (METH:METH) did not show activated microglia. Interestingly, GFAP expression remained elevated in rats exposed to METH at PND60 (METH:Saline), and was not elevated further in resistant rats treated for the second time with METH (METH:METH). These data suggest that astrocytes remain reactive up to 30 days post-METH exposure. Additionally, these data indicate that astrocyte reactivity does not reflect acute, METH-induced DA terminal toxicity, whereas microglial reactivity does. PMID:23414433

  11. Anti-aging effects of guanosine in glial cells.

    PubMed

    Souza, Débora Guerini; Bellaver, Bruna; Bobermin, Larissa Daniele; Souza, Diogo Onofre; Quincozes-Santos, André

    2016-12-01

    Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality. Thus, the search for molecules able to reduce the glial dysfunction associated with aging may represent an approach for avoiding the onset of age-related neurological diseases. Hence, the aim of this study was to evaluate the anti-aging effects of guanosine, using primary astrocyte cultures from newborn, adult, and aged Wistar rats. Concomitantly, we evaluated the role of heme oxygenase 1 (HO-1) in guanosine-mediated glioprotection. We observed age-dependent changes in glutamate uptake, glutamine synthetase (GS) activity, the glutathione (GSH) system, pro-inflammatory cytokine (tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)) release, and the transcriptional activity of nuclear factor kB (NFkB), which were prevented by guanosine in an HO-1-dependent manner. Our findings suggest guanosine to be a promising therapeutic agent able to provide glioprotection during the aging process. Thus, this study contributes to the understanding of the cellular and molecular mechanisms of guanosine in the aging process.

  12. Glial activation in the collagenase model of nociception associated with osteoarthritis

    PubMed Central

    Almeida, Lígia; Potes, Catarina S; Ferreira, Ana Rita; Castro-Lopes, José M; Ferreira-Gomes, Joana; Neto, Fani L

    2017-01-01

    Background Experimental osteoarthritis entails neuropathic-like changes in dorsal root ganglia (DRG) neurons. Since glial activation has emerged as a key player in nociception, being reported in numerous models of neuropathic pain, we aimed at evaluating if glial cell activation may also occur in the DRG and spinal cord of rats with osteoarthritis induced by intra-articular injection of collagenase. Methods Osteoarthritis was induced by two injections, separated by three days, of 500 U of type II collagenase into the knee joint of rats. Movement-induced nociception was evaluated by the Knee-Bend and CatWalk tests during the following six weeks. Glial fibrillary acidic protein (GFAP) expression in satellite glial cells of the DRG was assessed by immunofluorescence and Western Blot analysis; the pattern of GFAP and activating transcription factor-3 (ATF-3) expression was also compared through double immunofluorescence analysis. GFAP expression in astrocytes and IBA-1 expression in microglia of the L3–L5 spinal cord segments was assessed by immunohistochemistry and Western Blot analysis. The effect of the intrathecal administration of fluorocitrate, an inhibitor of glial activation, on movement-induced nociception was evaluated six weeks after the first collagenase injection. Results GFAP expression in satellite glial cells of collagenase-injected animals was significantly increased six weeks after osteoarthritis induction. Double immunofluorescence showed GFAP upregulation in satellite glial cells surrounding ATF-3-positive neurons. In the spinal cord of collagenase-injected animals, an ipsilateral upregulation of GFAP and IBA-1 was also observed. The inhibition of glial activation with fluorocitrate decreased movement- and loading-induced nociception. Conclusion Collagenase-induced knee osteoarthritis leads to the development of nociception associated with movement of the affected joint and to the activation of glial cells in both the DRG and the spinal cord

  13. Glial activation in the collagenase model of nociception associated with osteoarthritis.

    PubMed

    Adães, Sara; Almeida, Lígia; Potes, Catarina S; Ferreira, Ana Rita; Castro-Lopes, José M; Ferreira-Gomes, Joana; Neto, Fani L

    2017-01-01

    Background Experimental osteoarthritis entails neuropathic-like changes in dorsal root ganglia (DRG) neurons. Since glial activation has emerged as a key player in nociception, being reported in numerous models of neuropathic pain, we aimed at evaluating if glial cell activation may also occur in the DRG and spinal cord of rats with osteoarthritis induced by intra-articular injection of collagenase. Methods Osteoarthritis was induced by two injections, separated by three days, of 500 U of type II collagenase into the knee joint of rats. Movement-induced nociception was evaluated by the Knee-Bend and CatWalk tests during the following six weeks. Glial fibrillary acidic protein (GFAP) expression in satellite glial cells of the DRG was assessed by immunofluorescence and Western Blot analysis; the pattern of GFAP and activating transcription factor-3 (ATF-3) expression was also compared through double immunofluorescence analysis. GFAP expression in astrocytes and IBA-1 expression in microglia of the L3-L5 spinal cord segments was assessed by immunohistochemistry and Western Blot analysis. The effect of the intrathecal administration of fluorocitrate, an inhibitor of glial activation, on movement-induced nociception was evaluated six weeks after the first collagenase injection. Results GFAP expression in satellite glial cells of collagenase-injected animals was significantly increased six weeks after osteoarthritis induction. Double immunofluorescence showed GFAP upregulation in satellite glial cells surrounding ATF-3-positive neurons. In the spinal cord of collagenase-injected animals, an ipsilateral upregulation of GFAP and IBA-1 was also observed. The inhibition of glial activation with fluorocitrate decreased movement- and loading-induced nociception. Conclusion Collagenase-induced knee osteoarthritis leads to the development of nociception associated with movement of the affected joint and to the activation of glial cells in both the DRG and the spinal cord

  14. Glial potassium channels activated by neuronal firing or intracellular cyclic AMP in Helix.

    PubMed

    Gommerat, I; Gola, M

    1996-09-15

    1. Cell-attached and whole cell patch clamp experiments were performed on satellite glial cells adhering to the cell body of neurones in situ within the nervous system of the snail Helix pomatia. The underlying neurone was under current or voltage-clamp control. 2. Neuronal firing induced a delayed (20-30 s) persistent (3-4 min) increase in the opening probability of glial K+ channels. The channels were also activated by perfusing the ganglion with a depolarizing high-K+ saline, except when the underlying neurone was prevented from depolarizing under voltage-clamp conditions. 3. Two K(+)-selective channels were detected in the glial membrane. The channel responding to neuronal firing was present in 95% of the patches (n = 393). It had a unitary conductance of 56 pS, a Na+ :K+ permeability ratio < 0.02 and displayed slight inward rectification in symmetrical [K+] conditions. It was sensitive to TEA, Ba2+ and Cs+. The following results refer to this channel as studied in the cell-attached configuration. 4. The glial K+ channel was activated by bath application of the membrane-permeant cyclic AMP derivatives 8-bromo-cAMP and dibutyryl-cAMP, the adenylyl cyclase activator forskolin and the diesterase inhibitors IBMX, theophylline and caffeine. It was insensitive to cyclic GMP activators and to conditions that might alter the intracellular [Ca2+] (ionomycin, low-Ca2+ saline and Ca2+ channel blockers). 5. The forskolin-induced changes in channel behaviour (open and closed time distributions, burst duration, short and long gaps within bursts) could be accounted for by a four-state model (3 closed states, 1 open state) by simply changing one of the six rate parameters. 6. The present results suggest that the signal sent by an active neurone to satellite glial cells is confined to the glial cells round that neurone. The effect of this signal on the class of glial K+ channels studied can be mimicked by an increase in glial cAMP concentration. The subsequent delayed opening

  15. Glial potassium channels activated by neuronal firing or intracellular cyclic AMP in Helix.

    PubMed Central

    Gommerat, I; Gola, M

    1996-01-01

    1. Cell-attached and whole cell patch clamp experiments were performed on satellite glial cells adhering to the cell body of neurones in situ within the nervous system of the snail Helix pomatia. The underlying neurone was under current or voltage-clamp control. 2. Neuronal firing induced a delayed (20-30 s) persistent (3-4 min) increase in the opening probability of glial K+ channels. The channels were also activated by perfusing the ganglion with a depolarizing high-K+ saline, except when the underlying neurone was prevented from depolarizing under voltage-clamp conditions. 3. Two K(+)-selective channels were detected in the glial membrane. The channel responding to neuronal firing was present in 95% of the patches (n = 393). It had a unitary conductance of 56 pS, a Na+ :K+ permeability ratio < 0.02 and displayed slight inward rectification in symmetrical [K+] conditions. It was sensitive to TEA, Ba2+ and Cs+. The following results refer to this channel as studied in the cell-attached configuration. 4. The glial K+ channel was activated by bath application of the membrane-permeant cyclic AMP derivatives 8-bromo-cAMP and dibutyryl-cAMP, the adenylyl cyclase activator forskolin and the diesterase inhibitors IBMX, theophylline and caffeine. It was insensitive to cyclic GMP activators and to conditions that might alter the intracellular [Ca2+] (ionomycin, low-Ca2+ saline and Ca2+ channel blockers). 5. The forskolin-induced changes in channel behaviour (open and closed time distributions, burst duration, short and long gaps within bursts) could be accounted for by a four-state model (3 closed states, 1 open state) by simply changing one of the six rate parameters. 6. The present results suggest that the signal sent by an active neurone to satellite glial cells is confined to the glial cells round that neurone. The effect of this signal on the class of glial K+ channels studied can be mimicked by an increase in glial cAMP concentration. The subsequent delayed opening

  16. Observations on glial inclusion bodies in a case of acute disseminated sclerosis

    PubMed Central

    Field, E. J.; Miller, Henry; Russell, Dorothy S.

    1962-01-01

    An unusual rod-like structure enclosed within a vacuole is described as occurring in enlarged glial cells associated with the lesions encountered in an uncommonly acute case of multiple sclerosis apparently heralded by an attack of `viral encephalitis'. Similar bodies were not found in a variety of other enlarged glial cells. An encapsulated `grape-fruit' like structure was also seen. Images PMID:13892761

  17. TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain.

    PubMed

    Yan, Sen; Wang, Chuan-En; Wei, Wenjie; Gaertig, Marta A; Lai, Liangxue; Li, Shihua; Li, Xiao-Jiang

    2014-05-15

    Mutations in TAR DNA-binding protein 43 (TDP-43) are associated with familial forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Although recent studies have revealed that mutant TDP-43 in neuronal and glial cells is toxic, how mutant TDP-43 causes primarily neuronal degeneration in an age-dependent manner remains unclear. Using adeno-associated virus (AAV) that expresses mutant TDP-43 (M337V) ubiquitously, we found that mutant TDP-43 accumulates preferentially in neuronal cells in the postnatal mouse brain. We then ubiquitously or selectively expressed mutant TDP-43 in neuronal and glial cells in the striatum of adult mouse brains via stereotaxic injection of AAV vectors and found that it also preferentially accumulates in neuronal cells. Expression of mutant TDP-43 in neurons in the striatum causes more severe degeneration, earlier death and more robust symptoms in mice than expression of mutant TDP-43 in glial cells; however, aging increases the expression of mutant TDP-43 in glial cells, and expression of mutant TDP-43 in older mice caused earlier onset of phenotypes and more severe neuropathology than that in younger mice. Although expression of mutant TDP-43 in glial cells via stereotaxic injection does not lead to robust neurological phenotypes, systemic inhibition of the proteasome activity via MG132 in postnatal mice could exacerbate glial TDP-43-mediated toxicity and cause mice to die earlier. Consistently, this inhibition increases the expression of mutant TDP-43 in glial cells in mouse brains. Thus, the differential accumulation of mutant TDP-43 in neuronal versus glial cells contributes to the preferential toxicity of mutant TDP-43 in neuronal cells and age-dependent pathology.

  18. Molecular Mechanisms Mediating Involvement of Glial Cells in Brain Plastic Remodeling in Epilepsy.

    PubMed

    Khaspekov, L G; Frumkina, L E

    2017-03-01

    In this review we summarize published data on the involvement of glial cells in molecular mechanisms underlying brain plastic reorganization in epilepsy. The role of astrocytes as glial elements in pathological plasticity in epilepsy is discussed. Data on the involvement of aquaporin-4 in epileptogenic plastic changes and on participation of microglia and extracellular matrix in dysregulation of synaptic transmission and plastic remodeling in epileptic brain tissue are reviewed.

  19. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications.

    PubMed

    Grzesiak, Jakub; Marycz, Krzysztof; Szarek, Dariusz; Bednarz, Paulina; Laska, Jadwiga

    2015-01-01

    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane-polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane-polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells.

  20. Long-term glial reactivity in rat retinas ipsilateral and contralateral to experimental glaucoma.

    PubMed

    Kanamori, Akiyasu; Nakamura, Makoto; Nakanishi, Yoriko; Yamada, Yuko; Negi, Akira

    2005-07-01

    Although glaucoma is known to alter glial reactivity, the long-term effect of elevated intraocular pressure (IOP) on glial change has not been fully elucidated. This study aimed to examine how chronically elevated IOP induced by episcleral vein cauterization (EVC) in unilateral eyes affect reactivities of astrocytes and Müller cells of rats in the treated as well as contralateral eyes over time. EVC in unilateral eyes of Sprague-Dawley rats were performed to produce chronically elevated IOP. Flat mounted retina preparations were made at several points until 6 months, which were subjected to immunostaining for glial fibrillary acidic protein (GFAP). Retinal homogenates were one- or two-dimensionally electrophoresed, followed by GFAP immunoblotting. EVC significantly increased IOPs up to 27.8 from 13.1 mmHg, which gradually decreased over time. In flat mounted retinas, astrocytes lost but Müller cells gained GFAP immunoreactivity at 3 days after cauterization. The glial changes were partially reversed over time but last even after IOP normalization. In the contralateral eyes, similar glial changes gradually appeared at 1 month after EVC and thereafter. Immunoblotting demonstrated not only molecular size shifts but also alteration of isoelectric focusing of GFAP both in treated and contralateral retina as compared with age-matched control retina. EVC led to opposite reactions in astrocytes and Müller cells in terms of GFAP immunoreactivity. Late-onset glial reactivity also occurred in the contralateral retina.

  1. Glial kon/NG2 gene network for central nervous system repair

    PubMed Central

    Losada-Perez, Maria; Harrison, Neale; Hidalgo, Alicia

    2017-01-01

    The glial regenerative response to central nervous system (CNS) injury, although limited, can be harnessed to promote regeneration and repair. Injury provokes the proliferation of ensheathing glial cells, which can differentiate to remyelinate axons, and partially restore function. This response is evolutionarily conserved, strongly implying an underlying genetic mechanism. In mammals, it is elicited by NG2 glia, but most often newly generated cells fail to differentiate. Thus an important goal had been to find out how to promote glial differentiation following the proliferative response. A gene network involving Notch and prospero (pros) controls the balance between glial proliferation and differentiation in flies and mice, and promotes CNS repair at least in fruit-flies. A key missing link had been how to relate the function of NG2 to this gene network. Recent findings by Losada-Perez et al., published in JCB, demonstrated that the Drosophila NG2 homologue kon-tiki (kon) is functionally linked to Notch and pros in glia. By engaging in two feedback loops with Notch and Pros, in response to injury, Kon can regulate both glial cell number and glial shape homeostasis, essential for repair. Drosophila offers powerful genetics to unravel the control of stem and progenitor cells for regeneration and repair. PMID:28250735

  2. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain.

    PubMed

    Saito, Mariko; Chakraborty, Goutam; Hui, Maria; Masiello, Kurt; Saito, Mitsuo

    2016-08-16

    Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD). While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy). Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7) mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

  3. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

    PubMed Central

    Saito, Mariko; Chakraborty, Goutam; Hui, Maria; Masiello, Kurt; Saito, Mitsuo

    2016-01-01

    Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD). While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy). Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7) mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain. PMID:27537918

  4. The glia doctrine: addressing the role of glial cells in healthy brain ageing.

    PubMed

    Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

    2013-10-01

    Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction.

  5. ATM kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila.

    PubMed

    Petersen, Andrew J; Rimkus, Stacey A; Wassarman, David A

    2012-03-13

    To investigate the mechanistic basis for central nervous system (CNS) neurodegeneration in the disease ataxia-telangiectasia (A-T), we analyzed flies mutant for the causative gene A-T mutated (ATM). ATM encodes a protein kinase that functions to monitor the genomic integrity of cells and control cell cycle, DNA repair, and apoptosis programs. Mutation of the C-terminal amino acid in Drosophila ATM inhibited the kinase activity and caused neuron and glial cell death in the adult brain and a reduction in mobility and longevity. These data indicate that reduced ATM kinase activity is sufficient to cause neurodegeneration in A-T. ATM kinase mutant flies also had elevated expression of innate immune response genes in glial cells. ATM knockdown in glial cells, but not neurons, was sufficient to cause neuron and glial cell death, a reduction in mobility and longevity, and elevated expression of innate immune response genes in glial cells, indicating that a non-cell-autonomous mechanism contributes to neurodegeneration in A-T. Taken together, these data suggest that early-onset CNS neurodegeneration in A-T is similar to late-onset CNS neurodegeneration in diseases such as Alzheimer's in which uncontrolled inflammatory response mediated by glial cells drives neurodegeneration.

  6. Soluble guanylyl cyclase is involved in PDT-induced injury of crayfish glial cells

    NASA Astrophysics Data System (ADS)

    Kovaleva, V. D.; Uzdensky, A. B.

    2016-04-01

    Photodynamic therapy (PDT) is a potential tool for selective destruction of malignant brain tumors. However, not only malignant but also healthy neurons and glial cells may be damaged during PDT. Nitric oxide is an important modulator of cell viability and intercellular neuroglial communications. NO have been already shown to participate in PDT-induced injury of neurons and glial cells. As soluble guanylyl cyclase is the only known receptor for NO, we have studied the possible role of soluble guanylyl cyclase in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Using inhibitory analysis we have shown that during PDT soluble guanylyl cyclase, probably, has proapoptotic and antinecrotic effect on the glial cells of the isolated crayfish stretch receptor. Proapoptotic effect of soluble guanylyl cyclase could be mediated by protein kinase G (PKG). Thus, the involvement of NO/sGC/cGMP/PKG signaling pathway in PDT-induced apoptosis of glial cells was indirectly demonstrated.

  7. Loss of Glial Neurofascin155 Delays Developmental Synapse Elimination at the Neuromuscular Junction

    PubMed Central

    Roche, Sarah L.; Sherman, Diane L.; Dissanayake, Kosala; Soucy, Geneviève; Desmazieres, Anne; Lamont, Douglas J.; Peles, Elior; Julien, Jean-Pierre; Wishart, Thomas M.; Ribchester, Richard R.; Brophy, Peter J.

    2014-01-01

    Postnatal synapse elimination plays a critical role in sculpting and refining neural connectivity throughout the central and peripheral nervous systems, including the removal of supernumerary axonal inputs from neuromuscular junctions (NMJs). Here, we reveal a novel and important role for myelinating glia in regulating synapse elimination at the mouse NMJ, where loss of a single glial cell protein, the glial isoform of neurofascin (Nfasc155), was sufficient to disrupt postnatal remodeling of synaptic circuitry. Neuromuscular synapses were formed normally in mice lacking Nfasc155, including the establishment of robust neuromuscular synaptic transmission. However, loss of Nfasc155 was sufficient to cause a robust delay in postnatal synapse elimination at the NMJ across all muscle groups examined. Nfasc155 regulated neuronal remodeling independently of its canonical role in forming paranodal axo–glial junctions, as synapse elimination occurred normally in mice lacking the axonal paranodal protein Caspr. Rather, high-resolution proteomic screens revealed that loss of Nfasc155 from glial cells was sufficient to disrupt neuronal cytoskeletal organization and trafficking pathways, resulting in reduced levels of neurofilament light (NF-L) protein in distal axons and motor nerve terminals. Mice lacking NF-L recapitulated the delayed synapse elimination phenotype observed in mice lacking Nfasc155, suggesting that glial cells regulate synapse elimination, at least in part, through modulation of the axonal cytoskeleton. Together, our study reveals a glial cell-dependent pathway regulating the sculpting of neuronal connectivity and synaptic circuitry in the peripheral nervous system. PMID:25232125

  8. Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts

    PubMed Central

    Fellner, Lisa; Jellinger, Kurt A.; Wenning, Gregor K.; Stefanova, Nadia

    2016-01-01

    Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are adult onset neurodegenerative disorders characterised by prominent intracellular α-synuclein aggregates (α-synucleinopathies). The glial contribution to neurodegeneration in α-synucleinopathies was largely underestimated until recently. However, brains of PD and DLB patients exhibit not only neuronal inclusions such as Lewy bodies or Lewy neurites but also glial α-synuclein aggregates. Accumulating experimental evidence in PD models suggests that astrogliosis and microgliosis act as important mediators of neurodegeneration playing a pivotal role in both disease initiation and progression. In MSA, oligodendrocytes are intriguingly affected by aberrant cytoplasmic accumulation of α-synuclein (glial cytoplasmic inclusions, Papp-Lantos bodies). Converging evidence from human postmortem studies and transgenic MSA models suggests that oligodendroglial dysfunction both triggers and exacerbates neuronal degeneration. This review summarises the wide range of responsibilities of astroglia, microglia and oligodendroglia in the healthy brain and the changes in glial function associated with ageing. We then provide a critical analysis of the role of glia in α-synucleinopathies including putative mechanisms promoting a chronically diseased glial microenvironment which can lead to detrimental neuronal changes, including cell loss. Finally, major therapeutic strategies targeting glial pathology in α-synucleinopathies as well as current pitfalls for disease-modification in clinical trials are discussed. PMID:21562886

  9. Photodynamic injury of isolated crayfish neuron and surrounding glial cells: the role of p53

    NASA Astrophysics Data System (ADS)

    Sharifulina, S. A.; Uzdensky, A. B.

    2015-03-01

    The pro-apoptotic transcription factor p53 is involved in cell responses to injurious impacts. Using its inhibitor pifithrin- α and activators tenovin-1, RITA and WR-1065, we studied its potential participation in inactivation and death of isolated crayfish mechanoreceptor neuron and satellite glial cells induced by photodynamic treatment, a strong inducer of oxidative stress. In dark, p53 activation by tenovin-1 or WR-1065 shortened activity of isolated neurons. Tenovin-1 and WR-1065 induced apoptosis of glial cells, whereas pifithrin-α was anti-apoptotic. Therefore, p53 mediated glial apoptosis and suppression of neuronal activity after axotomy. Tenovin-1 but not other p53 modulators induced necrosis of axotomized neurons and surrounding glia, possibly, through p53-independent pathway. Under photodynamic treatment, p53 activators tenovin-1 and RITA enhanced glial apoptosis indicating the pro-apoptotic activity of p53. Photoinduced necrosis of neurons and glia was suppressed by tenovin-1 and, paradoxically, by pifithrin-α. Modulation of photoinduced changes in the neuronal activity and necrosis of neurons and glia was possibly p53-independent. The different effects of p53 modulators on neuronal and glial responses to axotomy and photodynamic impact were apparently associated with different signaling pathways in neurons and glial cells.

  10. Intelligibility of Clear Speech: Effect of Instruction

    ERIC Educational Resources Information Center

    Lam, Jennifer; Tjaden, Kris

    2013-01-01

    Purpose: The authors investigated how clear speech instructions influence sentence intelligibility. Method: Twelve speakers produced sentences in habitual, clear, hearing impaired, and overenunciate conditions. Stimuli were amplitude normalized and mixed with multitalker babble for orthographic transcription by 40 listeners. The main analysis…

  11. Acoustics of Clear Speech: Effect of Instruction

    ERIC Educational Resources Information Center

    Lam, Jennifer; Tjaden, Kris; Wilding, Greg

    2012-01-01

    Purpose: This study investigated how different instructions for eliciting clear speech affected selected acoustic measures of speech. Method: Twelve speakers were audio-recorded reading 18 different sentences from the Assessment of Intelligibility of Dysarthric Speech (Yorkston & Beukelman, 1984). Sentences were produced in habitual, clear,…

  12. Constructing a Clear Path to Accomplished Teaching

    ERIC Educational Resources Information Center

    Berg, Jill Harrison

    2010-01-01

    Given the importance of quality teaching for student success, it is clear that every child needs to be able to receive instruction from a teacher who possesses the knowledge and skills for quality teaching--an accomplished teacher. It is less clear, however, how current teacher development policies and practices can ensure that all students will…

  13. Chemical Literature Exercises and Resources (CLEAR).

    ERIC Educational Resources Information Center

    Hostettler, John D.; And Others

    These materials were developed to make the structure and use of the chemical literature clear to chemistry students and to help them become independent and intelligent users of the library. The design of Chemical Literature Exercises and Resources (CLEAR) includes a users' note and five main parts: introduction to chemical literature, chemical…

  14. Identification and Characterization of Neuronal Precursors and Their Progeny From Human Fetal Tissue

    PubMed Central

    Piper, David R.; Mujtaba, Tahmina; Keyoung, Hansoo; Roy, Neeta S.; Goldman, Steven A.; Rao, Mahendra S.; Lucero, Mary T.

    2010-01-01

    We have examined primary human neuronal precursors (HNPs) from 18–22-week-old fetuses. We showed that E-NCAM/MAP2/β-III tubulin-immunoreactive neuronal precursors divide in vitro and could be induced to differentiate into mature neurons in 2 weeks. HNPs did not express nestin and differentiated slowly compared to rodent neuronal restricted precursors (NRPs, 5 days). Immunocytochemical and physiological analyses showed that HNPs could generate a heterogeneous population of neurons that expressed neurofilament-associated protein and various neurotransmitters, neurotransmitter synthesizing enzymes, voltage-gated ion channels, and ligand-gated neurotransmitter receptors and could fire action potentials. Undifferentiated and differentiated HNPs did not coexpress glial markers. Only a subset of cells that expressed GFP under the control of the Tα1 tubulin promoter was E-NCAM/β-III tubulin-immunoreactive, indicating nonexclusive overlap between these two HNP cell populations. Overall, HNPs resemble NRPs isolated from rodent tissue and appear to be a neuronal precursor population. PMID:11746353

  15. Unusual clear cell variant of epithelioid mesothelioma.

    PubMed

    Dessy, E; Falleni, M; Braidotti, P; Del Curto, B; Panigalli, T; Pietra, G G

    2001-12-01

    Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed.

  16. Preparation of superconductor precursor powders

    DOEpatents

    Bhattacharya, R.

    1998-08-04

    A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic and/or reduced particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of all metals in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products. 7 figs.

  17. Preparation of superconductor precursor powders

    DOEpatents

    Bhattacharya, Raghunath; Blaugher, Richard D.

    1995-01-01

    A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals, such as nitrate salts of thallium, barium, calcium, and copper, which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of thallium in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

  18. PAGOSA Sample Problem. Elastic Precursor

    SciTech Connect

    Weseloh, Wayne N.; Clancy, Sean Patrick

    2016-02-03

    A PAGOSA simulation of a flyer plate impact which produces an elastic precursor wave is examined. The simulation is compared to an analytic theory for the Mie-Grüneisen equation of state and an elastic-perfectly-plastic strength model.

  19. The involvement of NF-κB in PDT-induced death of crayfish glial and nerve cells

    NASA Astrophysics Data System (ADS)

    Berezhnaya, E. V.; Neginskaya, M. A.; Kovaleva, V. D.; Rudkovskii, M. V.; Uzdensky, A. B.

    2015-03-01

    Photodynamic therapy (PDT) is used for selective destruction of cells, in particular, for treatment of brain tumors. However, photodynamic treatment damages not only tumor cells, but also healthy neurons and glial cells. To study the possible role of NF-κB in photodynamic injury of neurons and glial cells, we investigated the combined effect of photodynamic treatment and NF-κB modulators: activator betulinic acid, or inhibitors parthenolide and CAPE on an isolated crayfish stretch receptor consisting of a single neuron surrounded by glial cells. A laser diode (670 nm, 0.4 W/cm2) was used as a light source. The inhibition of NF-κB during PDT increased the duration of neuron firing and glial necrosis and decreased neuron necrosis and glial apoptosis. The activation of NF-κB during PDT increased neuron necrosis and glial apoptosis and decreased glial necrosis. The difference between the effects of NF-κB modulators on photosensitized neurons and glial cells indicates the difference in NF-κB-mediated signaling pathways in these cell types. Thus, NF-κB is involved in PDT-induced shortening of neuron firing, neuronal and glial necrosis, and apoptosis of glial cells.

  20. Three-Dimensional Regulation of Radial Glial Functions by Lis1-Nde1 and Dystrophin Glycoprotein Complexes

    PubMed Central

    Pawlisz, Ashley S.; Feng, Yuanyi

    2011-01-01

    Radial glial cells (RGCs) are distinctive neural stem cells with an extraordinary slender bipolar morphology and dual functions as precursors and migration scaffolds for cortical neurons. Here we show a novel mechanism by which the Lis1-Nde1 complex maintains RGC functions through stabilizing the dystrophin/dystroglycan glycoprotein complex (DGC). A direct interaction between Nde1 and utrophin/dystrophin allows for the assembly of a multi-protein complex that links the cytoskeleton to the extracellular matrix of RGCs to stabilize their lateral membrane, cell-cell adhesion, and radial morphology. Lis1-Nde1 mutations destabilized the DGC and resulted in deformed, disjointed RGCs and disrupted basal lamina. Besides impaired RGC self-renewal and neuronal migration arrests, Lis1-Nde1 deficiencies also led to neuronal over-migration. Additional to phenotypic resemblances of Lis1-Nde1 with DGC, strong synergistic interactions were found between Nde1 and dystroglycan in RGCs. As functional insufficiencies of LIS1, NDE1, and dystroglycan all cause lissencephaly syndromes, our data demonstrated that a three-dimensional regulation of RGC's cytoarchitecture by the Lis1-Nde1-DGC complex determines the number and spatial organization of cortical neurons as well as the size and shape of the cerebral cortex. PMID:22028625

  1. Opposite patterns of age-associated changes in neurons and glial cells of the thalamus of human brain.

    PubMed

    Guidolin, D; Zunarelli, E; Genedani, S; Trentini, G P; De Gaetani, C; Fuxe, K; Benegiamo, C; Agnati, L F

    2008-06-01

    In an autopsy series of 19 individuals, age-ranged 24-94, a relatively age-spared region, the anterior-ventral thalamus, was analyzed by immunohistochemical techniques to visualize neurons (neurofilament protein), astrocytes (glial fibrillary acidic protein), microglial cells (CD68) and amyloid precursor protein. The pattern of immunoreactivity was determined by surface fractal dimension and lacunarity, the size by the field area (FA) and the spatial uniformity by the uniformity index. From the normalized FA values of immunoreactivity for the four markers studied, a global parameter was defined to give an overall characterization of the age-dependent changes in the glio-neuronal networks. A significant exponential decline of the GP was observed with increasing age. This finding suggests that early in life (age<50 years) an adaptive response might be triggered, involving the glio-neuronal networks in plastic adaptive adjustments to cope with the environmental challenges and the continuous wearing off of the neuronal structures. The slow decay of the GP observed in a later phase (age>70 years) could be due to the non-trophic reserve still available.

  2. Migratory capacity of the cell line RN33B and the host glial cell response after subretinal transplantation to normal adult rats.

    PubMed

    Wojciechowski, Anita Blixt; Englund, Ulrica; Lundberg, Cecilia; Warfvinge, Karin

    2004-07-01

    As previously reported, the brain-derived precursor cell line RN33B has a great capacity to migrate when transplanted to adult brain or retina. This cell line is immortalized with the SV40 large T-antigen and carries the reporter gene LacZ and the green fluorescent protein GFP. In the present study, the precursor cells were transplanted to the subretinal space of adult rats and investigated early after grafting. The purpose was to demonstrate the migration of the grafted cells from the subretinal space into the retina and the glial cell response of the host retina. Detachment caused by the transplantation method was persistent up to 4 days after transplantation, and then reattachment occurred. The grafted cells were shown to migrate in between the photoreceptor cells before entering into the plexiform layers. Molecules involved in migration of immature neuronal cells as the polysialylated neural cell adhesion molecule (PSA-NCAM) and the collapsing response-mediated protein 4 (TUC-4) was found in the plexiform layers of the host retina, but not in the grafted cells. The expression of the intermediate filaments GFAP, vimentin, and nestin was intensely upregulated immediately after transplantation. A less pronounced upregulation was observed on sham-operated animals. In summary, the RN33B cell line migrated promptly posttransplantation and settled preferably into the plexiform layers of the retina, the same layers where the migration cues PSA-NCAM and TUC-4 were established. In addition, both the transplantation method per se and the implanted cells caused an intense glial cell response by the host retina.

  3. Mathematical modeling of chemotaxis and glial scarring around implanted electrodes

    NASA Astrophysics Data System (ADS)

    Silchenko, Alexander N.; Tass, Peter A.

    2015-02-01

    It is well known that the implantation of electrodes for deep brain stimulation or microelectrode probes for the recording of neuronal activity is always accompanied by the response of the brain’s immune system leading to the formation of a glial scar around the implantation sites. The implantation of electrodes causes massive release of adenosine-5‧-triphosphate (ATP) and different cytokines into the extracellular space and activates the microglia. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y2,12 as well as A3A/A2A adenosine receptors. The size and density of an insulating sheath around the electrode, formed by microglial cells, are important criteria for the optimization of the signal-to-noise ratio during microelectrode recordings or parameters of electrical current delivered to the brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards implanted electrodes as well as the possible impact of an anti-inflammatory coating consisting of the interleukin-1 receptor antagonist. We present a model describing the formation of a stable aggregate around the electrode due to the joint chemo-attractive action of ATP and ADP and the mixed influence of extracellular adenosine. The bioactive coating is modeled as a source of chemo-repellent located near the electrode surface. The obtained analytical and numerical results allowed us to reveal the dependences of size and spatial location of the insulating sheath on the amount of released ATP and estimate the impact of immune suppressive coating on the scarring process.

  4. Fractalkine mediates inflammatory pain through activation of satellite glial cells.

    PubMed

    Souza, Guilherme R; Talbot, Jhimmy; Lotufo, Celina M; Cunha, Fernando Q; Cunha, Thiago M; Ferreira, Sérgio H

    2013-07-02

    The activation of the satellite glial cells (SGCs) surrounding the dorsal root ganglion (DRG) neurons appears to play a role in pathological pain. We tested the hypothesis that fractalkine, which is constitutively expressed by primary nociceptive neurons, is the link between peripheral inflammation and the activation of SGCs and is thus responsible for the genesis of the inflammatory pain. The injection of carrageenin into the rat hind paw induced a decrease in the mechanical nociceptive threshold (hypernociception), which was associated with an increase in mRNA and GFAP protein expression in the DRG. Both events were inhibited by anti-fractalkine antibody administered directly into the DRG (L5) [intraganglionar (i.gl.)]. The administration of fractalkine into the DRG (L5) produced mechanical hypernociception in a dose-, time-, and CX3C receptor-1 (CX3CR1)-dependent manner. Fractalkine's hypernociceptive effect appears to be indirect, as it was reduced by local treatment with anti-TNF-α antibody, IL-1-receptor antagonist, or indomethacin. Accordingly, the in vitro incubation of isolated and cultured SGC with fractalkine induced the production/release of TNF-α, IL-1β, and prostaglandin E2. Finally, treatment with i.gl. fluorocitrate blocked fractalkine (i.gl.)- and carrageenin (paw)-induced hypernociception. Overall, these results suggest that, during peripheral inflammation, fractalkine is released in the DRG and contributes to the genesis of inflammatory hypernociception. Fractalkine's effect appears to be dependent on the activation of the SGCs, leading to the production of TNFα, IL-1β, and prostanoids, which are likely responsible for the maintenance of inflammatory pain. Thus, these results indicate that the inhibition of fractalkine/CX3CR1 signaling in SGCs may serve as a target to control inflammatory pain.

  5. 17 CFR 20.3 - Clearing organizations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...; (13) Gross long non-delta-adjusted swaption positions; and (14) Gross short non-delta-adjusted... organizations shall report end of reporting day settlement prices for each cleared product and deltas for...

  6. 17 CFR 20.3 - Clearing organizations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...; (13) Gross long non-delta-adjusted swaption positions; and (14) Gross short non-delta-adjusted... organizations shall report end of reporting day settlement prices for each cleared product and deltas for...

  7. 17 CFR 20.3 - Clearing organizations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...; (13) Gross long non-delta-adjusted swaption positions; and (14) Gross short non-delta-adjusted... organizations shall report end of reporting day settlement prices for each cleared product and deltas for...

  8. Clear Corneal Incision in Cataract Surgery

    PubMed Central

    Al Mahmood, Ammar M.; Al-Swailem, Samar A.; Behrens, Ashley

    2014-01-01

    Since the introduction of sutureless clear corneal cataract incisions, the procedure has gained increasing popularity worldwide because it offers several advantages over the traditional sutured scleral tunnels and limbal incisions. Some of these benefits include lack of conjunctival trauma, less discomfort and bleeding, absence of suture-induced astigmatism, and faster visual rehabilitation. However, an increasing incidence of postoperative endophthalmitis after clear corneal cataract surgery has been reported. Different authors have shown a significant increase up to 15-fold in the incidence of endophthalmitis following clear corneal incision compared to scleral tunnels. The aim of this report is to review the advantages and disadvantages of clear corneal incisions in cataract surgery, emphasizing on wound construction recommendations based on published literature. PMID:24669142

  9. Flowmeter for Clear and Translucent Fluids

    NASA Technical Reports Server (NTRS)

    White, P. R.

    1985-01-01

    Transducer with only three moving parts senses flow of clear or translucent fluid. Displacement of diaphragm by force of flow detected electrooptically and displayed by panel meter or other device. Transducer used to measure flow of gasoline to automobile engine.

  10. Clear cell myoepithelial carcinoma ex pleomorphic adenoma.

    PubMed

    Rabade, Nikhil R; Goel, Naina A

    2014-01-01

    Pleomorphic adenoma is the most common epithelial neoplasm of lacrimal gland. A clear cell myoepithelial carcinoma arising in the background of pleomorphic adenoma is common in the salivary glands but very rare in the lacrimal glands. We report the case of a 27 year old man whose lacrimal gland pleomorphic adenoma recurred several times over a period of four years and ultimately evolved into a clear cell myoepithelial carcinoma ex pleomorphic adenoma.

  11. Single-channel and whole-cell recordings from on-neurone glial cells in Helix pomatia ganglia.

    PubMed

    Gommerat, I; Jacquet, G; Chagneux, H; Gola, M

    1993-11-01

    A procedure is described for performing patch-clamp recordings on satellite glial cells kept in place within the nervous ganglia in the mollusc Helix. Glial cell properties were deduced from whole-cell and cell-attached recordings. The glial membrane was found to contain densely packed inwardly rectifying K+ channels. Activation of the neurones, under either current-clamp or voltage-clamp conditions, depolarized the glial cell layer wrapped around the neurones and induced a delayed persistent increase in the K+ channel opening probability. These results suggest that the glial channels opened in response to a signal emanating from the active neurones. This preparation provides a useful means of detecting and analysing neurone-glial interactions at the cell and unitary channel levels.

  12. Impaired dental cytodifferentiation in glial cell-line derived growth factor (GDNF) deficient mice.

    PubMed

    de Vicente, J C; Cabo, R; Ciriaco, E; Laurà, R; Naves, F J; Silos-Santiago, I; Vega, J A

    2002-01-01

    Glial cell line-derived neurotrophic factor promotes the survival of multiple neuron types in the central and peripheral nervous system. Moreover, it plays a key role in the development of the enteric nervous system and in the kidney organogenesis. Glial cell line-derived neurotrophic factor and their receptors are expressed in the developing tooth as well as in the trigeminal ganglion. However, the precise role of this growth factor in tooth morphogenesis and cell differentiation, or in the development of trigeminal ganglion cells, is still elusive. Using structural and ultrastructural techniques we analyzed in detail the first molar tooth germ of glial cell line-derived neurotrophic factor deficient mice as well as the neuronal density in trigeminal ganglion. The length and width of first molar tooth germ in knockout deficient animals showed no differences in the knockout animals in comparison with age-matched heterozygous or wild-type littermates. Nevertheless, in mice lacking glial cell line-derived neurotrophic factor, both ameloblasts and odontoblasts failed to fully develop and differentiate, and the enamel matrix and predentin layers were absent. On the other hand, the number of trigeminal sensory neurons and the structure of the nerves supplying first molar tooth germ were largely normal. Present results suggest a new non-neuronal role for glial cell line-derived neurotrophic factor in tooth development. Glial cell line-derived neurotrophic factor seems not to be involved in tooth initiation and morphogenesis, whereas it seems essential for cytodifferentiation. Conversely, neither development of trigeminal neuron nor nerve fibers supplying teeth are directly dependent on glial cell line-derived neutrophic factor.

  13. Purinergic receptor activation inhibits osmotic glial cell swelling in the diabetic rat retina.

    PubMed

    Wurm, Antje; Iandiev, Ianors; Hollborn, Margrit; Wiedemann, Peter; Reichenbach, Andreas; Zimmermann, Herbert; Bringmann, Andreas; Pannicke, Thomas

    2008-10-01

    The anti-inflammatory glucocorticoid, triamcinolone acetonide, is used clinically for the rapid resolution of diabetic macular edema. Osmotic swelling of glial cells may contribute to the development of retinal edema. Triamcinolone inhibits the swelling of retinal glial cells of diabetic rats. Here, we determined whether the effect of triamcinolone is mediated by a receptor-dependent mechanism. Hyperglycemia was induced in rats with streptozotocin injection. After 6-10 months, the swelling properties of glial cells in retinal slices upon hypotonic challenge were determined. Nucleotide-degrading ecto-enzymes were immunostained in retinal slices and glial cells. Hypotonic challenge did not change the size of glial cell bodies from control retinas but induced swelling of cells from diabetic animals. Triamcinolone inhibited glial cell swelling; this effect was prevented by a selective antagonist of adenosine A1 receptors, an inhibitor of nucleoside transporters, inhibitors of adenylyl cyclase and protein kinase A activation, and inhibitors of potassium and chloride channels. In diabetic (but not control) retinas, the effect of triamcinolone apparently involves extracellular nucleotide degradation. Glial cells from diabetic retinas displayed immunolabeling against nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) which was not observed in control retinas. The mRNA expression for NTPDase1 was significantly increased in the retina of diabetic rats. It is suggested that triamcinolone induces the release and formation of endogenous adenosine that subsequently activates A1 receptors resulting in ion efflux through potassium and chloride channels and prevention of osmotic swelling. Whereas adenosine is liberated via facilitated transport in control retinas, an extracellular formation of adenosine contributes to the effect of triamcinolone in diabetic retinas.

  14. CO2 Efflux from Cleared Mangrove Peat

    PubMed Central

    Lovelock, Catherine E.; Ruess, Roger W.; Feller, Ilka C.

    2011-01-01

    Background CO2 emissions from cleared mangrove areas may be substantial, increasing the costs of continued losses of these ecosystems, particularly in mangroves that have highly organic soils. Methodology/Principal Findings We measured CO2 efflux from mangrove soils that had been cleared for up to 20 years on the islands of Twin Cays, Belize. We also disturbed these cleared peat soils to assess what disturbance of soils after clearing may have on CO2 efflux. CO2 efflux from soils declines from time of clearing from ∼10 600 tonnes km−2 year−1 in the first year to 3000 tonnes km2 year−1 after 20 years since clearing. Disturbing peat leads to short term increases in CO2 efflux (27 umol m−2 s−1), but this had returned to baseline levels within 2 days. Conclusions/Significance Deforesting mangroves that grow on peat soils results in CO2 emissions that are comparable to rates estimated for peat collapse in other tropical ecosystems. Preventing deforestation presents an opportunity for countries to benefit from carbon payments for preservation of threatened carbon stocks. PMID:21738628

  15. Skin optical clearing potential of disaccharides

    NASA Astrophysics Data System (ADS)

    Feng, Wei; Shi, Rui; Ma, Ning; Tuchina, Daria K.; Tuchin, Valery V.; Zhu, Dan

    2016-08-01

    Skin optical clearing can significantly enhance the ability of biomedical optical imaging. Some alcohols and sugars have been selected to be optical clearing agents (OCAs). In this work, we paid attention to the optical clearing potential of disaccharides. Sucrose and maltose were chosen as typical disaccharides to compare with fructose, an excellent monosaccharide-OCA, by using molecular dynamics simulation and an ex vivo experiment. The experimental results indicated that the optical clearing efficacy of skin increases linearly with the concentration for each OCA. Both the theoretical predication and experimental results revealed that the two disaccharides exerted a better optical clearing potential than fructose at the same concentration, and sucrose is optimal. Since maltose has an extremely low saturation concentration, the other two OCAs with saturation concentrations were treated topically on rat skin in vivo, and optical coherence tomography imaging was applied to monitor the optical clearing process. The results demonstrated that sucrose could cause a more significant increase in imaging depth and signal intensity than fructose.

  16. Precursor polymer compositions comprising polybenzimidazole

    SciTech Connect

    Klaehn, John R.; Peterson, Eric S.; Orme, Christopher J.

    2015-07-14

    Stable, high performance polymer compositions including polybenzimidazole (PBI) and a melamine-formaldehyde polymer, such as methylated, poly(melamine-co-formaldehyde), for forming structures such as films, fibers and bulky structures. The polymer compositions may be formed by combining polybenzimidazole with the melamine-formaldehyde polymer to form a precursor. The polybenzimidazole may be reacted and/or intertwined with the melamine-formaldehyde polymer to form the polymer composition. For example, a stable, free-standing film having a thickness of, for example, between about 5 .mu.m and about 30 .mu.m may be formed from the polymer composition. Such films may be used as gas separation membranes and may be submerged into water for extended periods without crazing and cracking. The polymer composition may also be used as a coating on substrates, such as metal and ceramics, or may be used for spinning fibers. Precursors for forming such polymer compositions are also disclosed.

  17. Soluble Precursor Route to Polyanilines

    DTIC Science & Technology

    1993-01-01

    condensation were not successful, but further work produced polymer under the following conditions: Synthesis Diketone I (2.40 g, 10.0 mmol) in 10 mL...goal of producing a processible form of the conducting polymer polyaniline (PANI), the Phase I program concentrated on development of the synthesis of...extension of the original research to a Phase II effort. Diketone - Diamine Polycondensation Towards a Soluble PAni Precursor To achieve the

  18. Accounting for nonmonotonic precursor duration effects with gain reduction in the temporal window modela

    PubMed Central

    Roverud, Elin; Strickland, Elizabeth A.

    2014-01-01

    The mechanisms of forward masking are not clearly understood. The temporal window model (TWM) proposes that masking occurs via a neural mechanism that integrates within a temporal window. The medial olivocochlear reflex (MOCR), a sound-evoked reflex that reduces cochlear amplifier gain, may also contribute to forward masking if the preceding sound reduces gain for the signal. Psychophysical evidence of gain reduction can be observed using a growth of masking (GOM) paradigm with an off-frequency forward masker and a precursor. The basilar membrane input/output (I/O) function is estimated from the GOM function, and the I/O function gain is reduced by the precursor. In this study, the effect of precursor duration on this gain reduction effect was examined for on- and off-frequency precursors. With on-frequency precursors, thresholds increased with increasing precursor duration, then decreased (rolled over) for longer durations. Thresholds with off-frequency precursors continued to increase with increasing precursor duration. These results are not consistent with solely neural masking, but may reflect gain reduction that selectively affects on-frequency stimuli. The TWM was modified to include history-dependent gain reduction to simulate the MOCR, called the temporal window model-gain reduction (TWM-GR). The TWM-GR predicted rollover and the differences with on- and off-frequency precursors whereas the TWM did not. PMID:24606271

  19. Diamond films grown from fullerene precursors

    SciTech Connect

    Gruen, D.M.; Zuiker, C.D.; Krauss, A.R.

    1995-07-01

    Fullerene precursors have been shown to result in the growth of diamond films from argon microwave plasmas. In contradistinction to most diamond films grown using conventional methane-hydrogen mixtures, the fullerene-generated films are nanocrystalline and smooth on the nanometer scale. They have recently been shown to have friction coefficients approaching the values of natural diamond. It is clearly important to understand the development of surface morphology during film growth from fullerene precursors and to elucidate the factors leading to surface roughness when hydrogen is present in the chemical vapor deposition (CVD) gas mixtures. To achieve these goals, we are measuring surface reflectivity of diamond films growing on silicon substrates over a wide range of plasma processing conditions. A model for the interpretation of the laser interferometric data has been developed, which allows one to determine film growth rate, rms surface roughness, and bulk losses due to scattering and absorption. The rms roughness values determined by reflectivity are in good agreement with atomic force microscope (AFM) measurements. A number of techniques, including high-resolution transmission electron microscopy (HRTEM) and near-edge x-ray absorption find structure (NEXAFS) measurements, have been used to characterize the films. A mechanism for diamond-film growth involving the C{sub 2} molecule as a growth species will be presented. The mechanism is based on (1) the observation that the optical emission spectra of the fullerene- containing plasmas are dominated by the Swan bands of C{sub 2} and (2) the ability of C{sub 2} to insert directly into C-H and C-C bonds with low activation barriers, as shown by recent theoretical calculations of reactions of C{sub 2} with carbon clusters.

  20. Nucleation precursors in protein crystallization

    PubMed Central

    Vekilov, Peter G.; Vorontsova, Maria A.

    2014-01-01

    Protein crystal nucleation is a central problem in biological crystallography and other areas of science, technology and medicine. Recent studies have demonstrated that protein crystal nuclei form within crucial precursors. Here, methods of detection and characterization of the precursors are reviewed: dynamic light scattering, atomic force microscopy and Brownian microscopy. Data for several proteins provided by these methods have demonstrated that the nucleation precursors are clusters consisting of protein-dense liquid, which are metastable with respect to the host protein solution. The clusters are several hundred nanometres in size, the cluster population occupies from 10−7 to 10−3 of the solution volume, and their properties in solutions supersaturated with respect to crystals are similar to those in homogeneous, i.e. undersaturated, solutions. The clusters exist owing to the conformation flexibility of the protein molecules, leading to exposure of hydrophobic surfaces and enhanced intermolecular binding. These results indicate that protein conformational flexibility might be the mechanism behind the metastable mesoscopic clusters and crystal nucleation. Investigations of the cluster properties are still in their infancy. Results on direct imaging of cluster behaviors and characterization of cluster mechanisms with a variety of proteins will soon lead to major breakthroughs in protein biophysics. PMID:24598910

  1. 76 FR 47529 - Customer Clearing Documentation and Timing of Acceptance for Clearing; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION 17 CFR Parts 1, 23, and 39 RIN 3038-AD51 Customer Clearing Documentation and Timing of Acceptance... August 1, 2011, regarding Customer Clearing Documentation and Timing of Acceptance for Clearing....

  2. 17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...,” only those rules that have been so approved. (b) Self-certification of rules. Proposed new or amended... of § 40.6 of this chapter. (c) Acceptance of new products for clearing. (1) A dormant derivatives...) Acceptance of certain new products for clearing. A derivatives clearing organization that accepts...

  3. Neuronal-glial interactions in rats fed a ketogenic diet.

    PubMed

    Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

    2006-01-01

    Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

  4. Glial cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence

    PubMed Central

    Ribeiro, Hélder; Carvalho, Tânia; Almeida, Luís; Marques, Rute; Misic, Ana M.; Bartow-McKenney, Casey; Larson, Denise M.; Pavan, William J.; Eberl, Gérard; Grice, Elizabeth A.; Veiga-Fernandes, Henrique

    2016-01-01

    Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers1. ILC3 development has been considered to be programmed1. Nevertheless, how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 sense their environment and control gut defence as part of a novel glial-ILC3-epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate II22, downstream of p38 MAPK/ERK-AKT cascade and STAT3 activation. Strikingly, ILC3 were adjacent to neurotrophic factor expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88 dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired ILC3-derived IL-22 and pronounced propensity to gut inflammation and infection. Our work sheds light into a novel multi-tissue defence unit, revealing glial cells as central hubs of neuron and innate immune regulation via neurotrophic factor signals. PMID:27409807

  5. Osmotic swelling characteristics of glial cells in the murine hippocampus, cerebellum, and retina in situ.

    PubMed

    Hirrlinger, Petra G; Wurm, Antje; Hirrlinger, Johannes; Bringmann, Andreas; Reichenbach, Andreas

    2008-05-01

    Glial cells are proposed to play a major role in the ionic and osmotic homeostasis in the CNS. Swelling of glial cells contributes to the development of edema in neural tissue under pathological conditions such as trauma and ischemia. In this study, we compared the osmotic swelling characteristics of murine hippocampal astrocytes, cerebellar Bergmann glial cells, and retinal Müller glial cells in acutely isolated tissue slices in response to hypoosmotic stress and pharmacological blockade of Kir channels. Hypoosmotic challenge induced an immediate swelling of somata in the majority of Bergmann glial cells and hippocampal astrocytes investigated, whereas Müller cell bodies displayed a substantial delay in the onset of swelling and hippocampal astroglial processes remained unaffected. Blockade of Kir channels under isoosmotic conditions had no swelling-inducing effect in Müller cell somata but caused a swelling in brain astrocytic somata and processes. Blockade of Kir channels under hypoosmotic conditions induced an immediate and strong swelling in Müller cell somata, but had no cumulative effect to brain astroglial somata. No regulatory volume decrease could be observed in all cell types. The data suggest that Kir channels are differently implicated in cell volume homeostasis of retinal Müller cells and brain astrocytes and that Müller cells and brain astrocytes differ in their osmotic swelling properties.

  6. Glial architecture of the ghost shark (Callorhinchus milii, Holocephali, Chondrichthyes) as revealed by different immunohistochemical markers.

    PubMed

    Ari, Csilla; Kálmán, Mihály

    2008-09-15

    This article presents the first study on the glial architecture of a representative species of Holocephali, Callorhinchus milii (ghost shark). Holocephali are a small subclass of Chondrichthyes, with only a few extant genera, and those are considered to have a brain organization more similar to squalomorph sharks than to galeomorph sharks, skates, and rays. Three different astroglial markers--glial fibrillary acidic protein, S-100 protein, and glutamine synthetase (GS)--were investigated by immunohistochemical methods, applying both diaminobenzidine (DAB) and fluorescent techniques. They revealed similar glial structures, although most of them were detected by immunohistochemical reaction against GS and visualized by DAB. The predominant elements were radial ependymoglia spanning the area between the ventricular and meningeal surfaces, as in squalomorph sharks. Other similar features were the light appearance of myelinated neural tracts devoid of immunoreactivity, and the glial architecture of the reticular formation of the brain stem, cerebellum, and tectum, the latter with recognizable layers. The immunoreactivity of the vascular walls was similar; however, it is believed that different cell types form the blood-brain barrier in chimeras and in elasmobranchs. Some glial structures, however, resembled those of skates, rays, and galeomorph sharks. In C. milii astrocyte-like elements were observed in the telencephalon, using GS and S-100, although typical astrocyte-rich regions were not found. In some areas, especially the telencephalon, not only endfeet but also cell bodies were observed to be attached to the meningeal surface, with processes extending into the brain substance.

  7. Signaling molecules regulating phenotypic conversions of astrocytes and glial scar formation in damaged nerve tissues.

    PubMed

    Koyama, Yutaka

    2014-12-01

    Phenotypic conversion of astrocytes from resting to reactive (i.e., astrocytic activation) occurs in numerous brain disorders. Astrocytic activation in severely damaged brain regions often leads to glial scar formation. Because astrocytic activation and glial scar largely affect the vulnerability and tissue repair of damaged brain, numerous studies have been made to clarify mechanisms regulating the astrocytic phenotype. The phenotypic conversion is accompanied by the increased expression of intermediate filament proteins and the induction of hypertrophy in reactive astrocytes. Severe brain damage results in proliferation and migration of reactive astrocytes, which lead to glial scar formations at the injured areas. Gliogenesis from neural progenitors in the adult brain is also involved in astrocytic activation and glial scar formation. Recent studies have shown that increased expression of connexin 43, aquaporin 4, matrix metalloproteinase 9, and integrins alter the function of astrocytes. The transcription factors: STAT3, OLIG2, SMAD, NF-κB, and Sp1 have been suggested to play regulatory roles in astrocytic activation and glial scar formation. In this review, I discuss the roles of these key molecules regulating the pathophysiological functions of reactive astrocytes.

  8. Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity.

    PubMed

    Croft, Wayne; Dobson, Katharine L; Bellamy, Tomas C

    2015-01-01

    The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes) have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours) rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology.

  9. Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity

    PubMed Central

    Croft, Wayne; Dobson, Katharine L.; Bellamy, Tomas C.

    2015-01-01

    The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes) have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours) rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology. PMID:26339509

  10. A transcriptional network controlling glial development in the Drosophila visual system.

    PubMed

    Bauke, Ann-Christin; Sasse, Sofia; Matzat, Till; Klämbt, Christian

    2015-06-15

    In the nervous system, glial cells need to be specified from a set of progenitor cells. In the developing Drosophila eye, perineurial glia proliferate and differentiate as wrapping glia in response to a neuronal signal conveyed by the FGF receptor pathway. To unravel the underlying transcriptional network we silenced all genes encoding predicted DNA-binding proteins in glial cells using RNAi. Dref and other factors of the TATA box-binding protein-related factor 2 (TRF2) complex were previously predicted to be involved in cellular metabolism and cell growth. Silencing of these genes impaired early glia proliferation and subsequent differentiation. Dref controls proliferation via activation of the Pdm3 transcription factor, whereas glial differentiation is regulated via Dref and the homeodomain protein Cut. Cut expression is controlled independently of Dref by FGF receptor activity. Loss- and gain-of-function studies show that Cut is required for glial differentiation and is sufficient to instruct the formation of membrane protrusions, a hallmark of wrapping glial morphology. Our work discloses a network of transcriptional regulators controlling the progression of a naïve perineurial glia towards the fully differentiated wrapping glia.

  11. Rapid radiative clearing of protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Haworth, Thomas J.; Clarke, Cathie J.; Owen, James E.

    2016-04-01

    The lack of observed transition discs with inner gas holes of radii greater than ˜50 au implies that protoplanetary discs dispersed from the inside out must remove gas from the outer regions rapidly. We investigate the role of photoevaporation in the final clearing of gas from low mass discs with inner holes. In particular, we study the so-called `thermal sweeping' mechanism which results in rapid clearing of the disc. Thermal sweeping was originally thought to arise when the radial and vertical pressure scalelengths at the X-ray heated inner edge of the disc match. We demonstrate that this criterion is not fundamental. Rather, thermal sweeping occurs when the pressure maximum at the inner edge of the dust heated disc falls below the maximum possible pressure of X-ray heated gas (which depends on the local X-ray flux). We derive new critical peak volume and surface density estimates for rapid radiative clearing which, in general, result in rapid dispersal happening less readily than in previous estimates. This less efficient clearing of discs by X-ray driven thermal sweeping leaves open the issue of what mechanism (e.g. far-ultraviolet heating) can clear gas from the outer disc sufficiently quickly to explain the non-detection of cold gas around weak line T Tauri stars.

  12. Cloud Clearing of Infrared Sounder Radiances.

    NASA Astrophysics Data System (ADS)

    Rizzi, R.; Serio, C.; Kelly, G.; Tramutoli, V.; McNally, A.

    1994-02-01

    R. RizziEuropean Centre for Medium-Range Weather Forecasts, Reading, England European Organization for the Exploitation of Meteorological Satellites, Darmstadt, Germany C. SerioDipartimento di Scienze Fisiche, Napoli, Italy G. KellyEuropean Centre for Medium-Range Weather Forecasts, Reading, England V. TramutoliDipartimento di Ingegneria e Fisica deil' Ambiente, Potenza, Italy A. McNallyEuropean Centre for Medium-Range Weather Forecasts, Reading, EnglandThe paper compares the performance of three different schemes for computing clear-sky brightness temperature from cloud-affected measurements. Both the ability to detect clouds and to estimate the equivalent clear-sky brightness temperature are examined. Simulated brightness temperatures computed from the ECMWF operational analysis are used as a reference, together with Advanced Very High Resolution Radiometer (AVHRR)-derived sea surface temperature and cloud content within High-Resolution Infrared Radiation Sounder (HIRS) fields of view. Cloud masks obtained from the cloud-detection schemes are compared with cloud masks obtained from AVHRR data; clear-column brightness temperatures for HIRS/2 channels 4, 7, and 13 are compared with the simulated ones; simulated clear-column brightness temperatures in the HIRS/2 window channel 8 are validated with equivalent products from AVHRR data. The comparison highlights some problems in the operational implementation of the NESDIS cloud-clearing scheme and with the operational filtering scheme of the United Kingdom Meteorological Office.

  13. Renal Clear Cell Carcinoma and Tonsil Metastasis

    PubMed Central

    Marcotullio, Dario; Iannella, Giannicola; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site. PMID:24455373

  14. Renal clear cell carcinoma and tonsil metastasis.

    PubMed

    Marcotullio, Dario; Iannella, Giannicola; Macri, Gian Franco; Marinelli, Caterina; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site.

  15. Optically clear film for tactile interfaces

    NASA Astrophysics Data System (ADS)

    Yairi, Micah

    2016-09-01

    For years, rigid plastics dominated as cover lenses in mobile and computing devices before being replaced by rigid glass sheets, which have become the current de facto standard. This is changing again. Optically clear, soft polymer films and film stacks now offer a promising alternative to glass. These polymer films provide a fundamentally different user experience, dramatically improving the user experience of writing and drawing, while also providing good durability. Tactus has developed an optically clear stack of polymer materials for use in a writing-first device. Details, usability studies, and performance data will be presented.

  16. Graft-copolymer-based approach to clear, durable, and anti-smudge polyurethane coatings.

    PubMed

    Rabnawaz, Muhammad; Liu, Guojun

    2015-05-26

    Clear anti-smudge coatings with a thickness of up to tens of micrometers have been prepared through a graft-copolymer-based approach from commercial precursors. The coatings repel water, diiodomethane, hexadecane, ink, and an artificial fingerprint liquid. In addition, they can be readily applied onto different substrates using different coating methods. These coatings could find applications in protecting hand-held electronic devices from fingerprints, windows from stains, and buildings from graffiti.

  17. Technical note: Methionine, a precursor of methane in living plants

    NASA Astrophysics Data System (ADS)

    Lenhart, K.; Althoff, F.; Greule, M.; Keppler, F.

    2014-11-01

    When terrestrial plants were identified as producers of the greenhouse gas methane, much discussion and debate ensued, not only about their contribution to the global methane budget, but also with regard to the validity of the observation itself. Although the phenomenon has now become more accepted for both living and dead plants, the mechanism of methane formation in living plants remains to be elucidated and its precursor compounds identified. We made use of stable isotope techniques to verify in vivo formation of methane and, in order to identify the carbon precursor, 13C-positionally labelled organic compounds were employed. Here we show that the amino acid L-methionine acts as a methane precursor in living plants. Employing 13C-labelled methionine clearly identified the sulphur-bound methyl group of methionine as a carbon precursor of methane released from lavender (Lavandula angustifolia). Furthermore, when lavender plants were stressed physically, methane release rates and the stable carbon isotope values of the emitted methane greatly increased. Our results provide additional support that plants possess a mechanism for methane production and suggest that methionine might play an important role in the formation of methane in living plants, particularly under stress conditions.

  18. Technical Note: Methionine, a precursor of methane in living plants

    NASA Astrophysics Data System (ADS)

    Lenhart, K.; Althoff, F.; Greule, M.; Keppler, F.

    2015-03-01

    When terrestrial plants were identified as producers of the greenhouse gas methane, much discussion and debate ensued not only about their contribution to the global methane budget but also with regard to the validity of the observation itself. Although the phenomenon has now become more accepted for both living and dead plants, the mechanism of methane formation in living plants remains to be elucidated and its precursor compounds to be identified. We made use of stable isotope techniques to verify the in vivo formation of methane, and, in order to identify the carbon precursor, 13C positionally labeled organic compounds were employed. Here we show that the amino acid L-methionine acts as a methane precursor in living plants. Employing 13C-labeled methionine clearly identified the sulfur-bound methyl group of methionine as a carbon precursor of methane released from lavender (Lavandula angustifolia). Furthermore, when lavender plants were stressed physically, methane release rates and the stable carbon isotope values of the emitted methane greatly increased. Our results provide additional support that plants possess a mechanism for methane production and suggest that methionine might play an important role in the formation of methane in living plants, particularly under stress conditions.

  19. The soft mechanical signature of glial scars in the central nervous system

    PubMed Central

    Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James; Franze, Kristian

    2017-01-01

    Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury. PMID:28317912

  20. TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.

    PubMed

    Smith, Cody J; Wheeler, Michael A; Marjoram, Lindsay; Bagnat, Michel; Deppmann, Christopher D; Kucenas, Sarah

    2017-04-05

    Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function.

  1. The soft mechanical signature of glial scars in the central nervous system

    NASA Astrophysics Data System (ADS)

    Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James; Franze, Kristian

    2017-03-01

    Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

  2. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    SciTech Connect

    Stiene-Martin, A.; Hauser, K.F. )

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 {mu}M met-enkephalin, 1 {mu}M met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined ({sup 3}H)-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in ({sup 3}H)-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture.

  3. Functional study of endothelin B receptors in satellite glial cells in trigeminal ganglia.

    PubMed

    Feldman-Goriachnik, Rachel; Hanani, Menachem

    2011-07-13

    There is immunohistochemical evidence for endothelin (ET) receptors in satellite glial cells in sensory ganglia, but there is no information on the function of these receptors. We used calcium imaging to study this question in isolated mouse trigeminal ganglia and found that satellite glial cells are highly sensitive to ET-1, with threshold at 0.05 nM. Responses displayed strong desensitization at ET-1 concentrations of more than 1 nM. A large component of the response persisted when Ca was deleted from the external medium, consistent with Ca release from internal stores. The use of receptor selective agents showed that the responses were mediated by ETB receptors. We conclude that satellite glial cells display endothelin receptors, which may participate in neuron-glia communications in the trigeminal ganglia.

  4. The Neurosteroid Allopregnanolone Modulates Specific Functions in Central and Peripheral Glial Cells

    PubMed Central

    Faroni, Alessandro; Magnaghi, Valerio

    2011-01-01

    Since the first observations on the existence of “neurosteroids” in the 1980s, our understanding of the importance of these endogenous steroids in the control of the central and peripheral nervous system (PNS) has increased progressively. Although most of the observations were made in neuronal cells, equally important are the effects that neurosteroids exert on glial cells. Among the different classes of neurosteroids acting on glial cells, the progesterone 5α-3α metabolite, allopregnanolone, displays a particular mechanism of action involving primarily the modulation of classic GABA receptors. In this review, we focus our attention on allopregnanolone because its effects on the physiology of glial cells of the central and PNS are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues. PMID:22654838

  5. Advancements in the Underlying Pathogenesis of Schizophrenia: Implications of DNA Methylation in Glial Cells

    PubMed Central

    Chen, Xing-Shu; Huang, Nanxin; Michael, Namaka; Xiao, Lan

    2015-01-01

    Schizophrenia (SZ) is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells. PMID:26696822

  6. Detection of glial fibrillary acidic protein and neurofilaments in the cerebrospinal fluid of patients with neurocysticercosis.

    PubMed

    Quintanar, J Luis; Franco, Luis Manuel; Salinas, Eva

    2003-07-01

    Neurocysticercosis (NCC) is an infection caused by Taenia solium larval metacestodes in the central nervous system. The glial fibrillary acidic protein (GFAP) and neurofilaments (NFs) can be used as markers of glial and neuronal damage, respectively. We studied the GFAP and NFs of 68, 160 and 200 kDa in the cerebrospinal fluid (CSF) of patients with NCC by Western blotting. Our results showed that patients with NCC had significantly elevated GFAP levels in the CSF compared with the control, whereas NFs of 68, 160 and 200 kDa were not detected in the CFS of NCC patients. We concluded that GFAP could be used as a marker of glial damage in the CFS of NCC patients.

  7. Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice.

    PubMed

    Han, Xiaoning; Chen, Michael; Wang, Fushun; Windrem, Martha; Wang, Su; Shanz, Steven; Xu, Qiwu; Oberheim, Nancy Ann; Bekar, Lane; Betstadt, Sarah; Silva, Alcino J; Takano, Takahiro; Goldman, Steven A; Nedergaard, Maiken

    2013-03-07

    Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.

  8. The "Big-Bang" for modern glial biology: Translation and comments on Pío del Río-Hortega 1919 series of papers on microglia.

    PubMed

    Sierra, Amanda; de Castro, Fernando; Del Río-Hortega, Juan; Rafael Iglesias-Rozas, José; Garrosa, Manuel; Kettenmann, Helmut

    2016-11-01

    The word "glia" was coined in the mid-19th century and defined as "the nerve glue". For decades, it was assumed to be a uniform matrix, until cell theorists raised the "neuron doctrine" which stipulated that nervous tissue was composed of individual cells. The term "astrocytes" was introduced in the late 19th century as a synonym for glial cells, but it was Santiago Ramón y Cajal who defined a "third element" distinct from glial cells (astrocytes) and neurons. It was not until 1919 when Pío del Río-Hortega, an alumnus of the Cajal School, introduced the modern terms we use today, and thoroughly described both "oligodendrocytes" and "microglia" to clearly distinguish them from astrocytes. In a series of four papers published that year in Spanish, Río-Hortega described the distribution and morphological phenotype of microglia. He also noted that these cells were the origin of the rod cells described earlier in pathologic tissue, and recognized that resting microglia transformed into an ameboid phenotype in different types of brain diseases and pathologies. He also noted the mesodermal origin of these cells and recognized their phagocytic capacity. We here provide the first English translation of these landmark series of papers, which paved the way for modern glial research. To heighten the value and accessibility of these classic papers and their original figures, an introduction to this critical period of neuroscience is provided, along with unpublished photographs. By adding comments to the translated text, we provide sufficient context so that contemporary scientists may fully appreciate it. GLIA 2016;64:1801-1840.

  9. Team Planning to CLEAR Up Problems

    ERIC Educational Resources Information Center

    Koehler, Nancy

    2006-01-01

    Professionals and parents need effective systems of teamwork for planning restorative outcomes with troubled children and youth. This article taps the resilient problem-solving process C*L*E*A*R, which is drawn from the Response Ability Pathways (RAP) curriculum. Participants examine the timeline of Challenges, Logic, Emotions, Actions, and…

  10. Development of a Clear Fiber Cherenkov Counter

    SciTech Connect

    Kaneko, N.; Han, S.; Ito, H.; Kawai, H.; Kobayashi, A.; Kodama, S.

    2015-07-01

    We have developed a new PID detector consists of clear fibers. PID efficiency was measured with 470 MeV e{sup +} beam. As a result, this detector with thickness of 5 cm has the PID efficiency of 95 %. (authors)

  11. Lake Mead--clear and vital

    USGS Publications Warehouse

    Wessells, Stephen M.; Rosen, Michael

    2013-01-01

    “Lake Mead – Clear and Vital” is a 13 minute documentary relating the crucial role of science in maintaining high water quality in Lake Mead. The program was produced coincident with release of the Lakes Mead and Mohave Circular a USGS publication covering past and on-going research in the lakes and tributaries of the Lake Mead National Recreation Area.

  12. Cloud clearing technology assessment: Final report

    SciTech Connect

    Not Available

    1988-03-01

    This report describes work done by W.J. Schafer Associates (WJSA) in support of the Long Pulse Chemical Laser (LPCL) project at the Los Alamos National Laboratory (LANL) in 1986-1987. The present document emphasizes work in the area of cloud hole boring. It consists of the Final Task reports for Tasks II (Meteorological Statistics), III (Cloud Clearing Concept Development) and IV (Fluid Mechanics). A separate report on ASAT analyses has been prepared and was delivered to the LANL program manager in April 1988. (This document contained results from several WJSA IRAD projects which are considered proprietary, hence they are not included in this Final Report Volume.) A third document describing work on laser kinetics analyses (Task I) will be provided separately. The present document is the Final Report for this subcontract. It describes work in the areas of cloud clearing mission analysis, cloud clearing experiment recommendations, and meteorological statistics relevant to cloud clearing and laser weapon propagation. 20 refs., 29 figs., 7 tabs.

  13. Clear Liquor Scrubbing with Anhydrite Production

    SciTech Connect

    Hargrove, O. W.; Carey, T. R.; Lowell, P. S.; Meserole, F. B.; Rhudy, R. G.; Feeley, Thomas J.

    1997-07-01

    The objective of this project to develop an advanced flue gas desulfurization (FGD) process that has decreased capital and operating costs, higher SO{sub 2} removal efficiency, and better by-product solids quality than existing, commercially available technology. A clear liquor process (which uses a scrubbing liquid with no solids) will be used to accomplish this objective rather than a slurry liquor process (which contains solids). This clear liquor scrubbing (CLS) project is focused on three research areas: (1) Development of a clear liquor scrubbing process that uses a clear solution to remove SO{sub 2} from flue gas and can be operated under inhibited-oxidation conditions; (2) Development of an anhydrite process that converts precipitated calcium sulfite to anhydrous calcium sulfate (anhydrite); and (3) Development of an alkali/humidification process to remove HCl from flue gas upstream of the FGD system. The anhydrite process also can be retrofit into existing FGD systems to produce a valuable by-product as an alternative to gypsum. This fits well into another of FETC's PRDA objectives of developing an advanced byproduct recovery subsystem capable of transforming SO{sub 2} into a useable byproduct or high-volume valuable commodities of interest. This paper describes the proposed processes, outlines the test approach, and preliminary Phase I test results.

  14. Clear Communication in the Digital Age

    ERIC Educational Resources Information Center

    Manchester, Bette

    2009-01-01

    One of the essential factors of successful integration of technology in classrooms is the role and relationship of the technology coordinator in supporting integration efforts. The vision for the use of technology in each school and district and the leadership role of the tech coordinator must be clear and understood by all. This article presents…

  15. Plant Histology: Clearing and the Optical Section.

    ERIC Educational Resources Information Center

    Freeman, H. E.

    1985-01-01

    Clearing is a simple and rapid technique in which 75 percent lactic acid is used to remove pigments and cytoplasmic contents of fresh leaves, enabling microscopic view of various internal leaf layers. Procedures for using the technique (which helps students gain a more thorough understanding of plant anatomy) are given. (DH)

  16. Still No Clear Answer on Graduation Prayer.

    ERIC Educational Resources Information Center

    Sendor, Benjamin

    1996-01-01

    Describes the Supreme Court graduation-prayer decision in "Lee v. Weisman" (1992) and implications of the "Jones v. Clear Creek Independent School District" case, which the Court decided not to review in 1993. Discusses the New Jersey graduation-prayer experiment and ruling of third District Circuit Court Judge Theodore A.…

  17. New Worlds Observer Precursor Mission

    NASA Astrophysics Data System (ADS)

    Lillie, C. F.; Lo, A. S.; Dailey, D.; Glassman, T. M.

    2007-06-01

    The New Worlds Observer architecture uses an external occulter to extinguish the on-axis light from a star and a separate telescope to collect the light from objects around that star, such as planets and debris disks. The separation of the starlight suppression capability from the photon collection capability makes the New Worlds Observer architecture very flexible. This paper describes NWO concepts ranging from low-cost precursor missions to Terrestrial Planet Finding (TPF) missions, and provides a path that extends beyond TPF to Planet-Imager and LifeFinder. Low cost precursor missions could be launched on a Minotaur using a small(~10 meter) occulter to work with a small(~0.5 m), telescope. Intermediate precursor missions could be accomplished by launching a larger occulter as a secondary payload to work with existing telescopes such as SOFIA or JWST. The former may allow direct detection of known giant planets, while the latter has the potential to discover Exo-Earths. A full TPF mission would consists of a large occulter working with a dedicated telescope; this can potentially find many terrestrial planets, as well as perform a host of ancillary astronomy investigations such as imaging debris disks and characterizing atmospheres of Jovian planets, as well as making general astrophysics observations. By utilizing the in space servicing capabilities that may be developed for the Exploration program, the lifetime of these occulters may be greatly extended by refueling and repair. In the future, larger occulters (>100 m) could be assembled on orbit. Thus, when coupled with a large telescope, the NWO architecture provides a path towards Lifefinder. NWO is a flexible architecture that allows scalability on all levels to suit the budget available for Exo-Planet Missions.

  18. Precursors of Short Gamma-Ray Bursts

    NASA Technical Reports Server (NTRS)

    Troja, E.; Rosswog, S.; Gehrels, N.

    2010-01-01

    We carried out a systematic search of precursors on the sample of short GRBs observed by Swift. We found that approx. 8-10% of short GRBs display such early episode of emission. One burst (GRB 090510) shows two precursor events, the former approx.13 s and the latter approx. 0.5 s before the GRB. We did not find any substantial difference between the precursor and the main GRB emission, and between short GRBs with and without precursors. We discuss possible mechanisms to reproduce the observed precursor emission within the scenario of compact object mergers. The implications of our results on quantum gravity constraints are also discussed.

  19. Nogo-a regulates neural precursor migration in the embryonic mouse cortex.

    PubMed

    Mathis, Carole; Schröter, Aileen; Thallmair, Michaela; Schwab, Martin E

    2010-10-01

    Although Nogo-A has been intensively studied for its inhibitory effect on axonal regeneration in the adult central nervous system, little is known about its function during brain development. In the embryonic mouse cortex, Nogo-A is expressed by radial precursor/glial cells and by tangentially migrating as well as postmigratory neurons. We studied radially migrating neuroblasts in wild-type and Nogo-A knockout (KO) mouse embryos. In vitro analysis showed that Nogo-A and its receptor components NgR, Lingo-1, TROY, and p75 are expressed in cells emigrating from embryonic forebrain-derived neurospheres. Live imaging revealed an increased cell motility when Nogo-A was knocked out or blocked with antibodies. Antibodies blocking NgR or Lingo-1 showed the same motility-enhancing effect supporting a direct role of surface Nogo-A on migration. Bromodeoxyuridine (BrdU) labeling of embryonic day (E)15.5 embryos demonstrated that Nogo-A influences the radial migration of neuronal precursors. At E17.5, the normal transient accumulation of radially migrating precursors within the subventricular zone was not detectable in the Nogo-A KO mouse cortex. At E19, migration to the upper cortical layers was disturbed. These findings suggest that Nogo-A and its receptor complex play a role in the interplay of adhesive and repulsive cell interactions in radial migration during cortical development.

  20. Neurogenesis and precursor cell differences in the dorsal and ventral adult canine hippocampus.

    PubMed

    Lowe, Aileen; Dalton, Marshall; Sidhu, Kuldip; Sachdev, Perminder; Reynolds, Brent; Valenzuela, Michael

    2015-04-23

    During evolution a unique anterior-posterior flexure posited the canine dentate gyrus in two distinct dorsal and ventral positions. We therefore sought to explore neurogenesis and neurogenic cell-related difference along the canine hippocampal dorsal-ventral axis. Post mortem histological analysis revealed 49.1% greater doublecortin (DCX)-positive cells and a 158.5% greater percentage of double labeled DCX-positive/neuronal nuclei (NeuN) positive cells in the dorsal subgranular zone compared to the ventral. We then show neural precursor cells isolated from fresh hippocampal tissue are capable of proliferating long term, and after differentiation, express neuronal and glial markers. Dorsal hippocampal isolates produced a 120.0% higher frequency of sphere-forming neural precursor cells compared to ventral hippocampal tissue. Histological DCX and neurosphere assay results were highly correlated. Overall, we provide the first evidence that the dorsal canine hippocampus has a markedly higher rate of adult neurogenesis than the ventral hippocampus, possibly related to a greater frequency of contributory neural precursor cells.

  1. Retinoic acid regulates the development of oligodendrocyte precursor cells in vitro.

    PubMed

    Laeng, P; Décimo, D; Pettmann, B; Janet, T; Labourdette, G

    1994-12-15

    Cultures of oligodendrocyte precursor cells can be grown from brain hemispheres of newborn rats. These cells, also called O-2A progenitor cells, can differentiate in vitro into oligodendrocytes or type 2 astrocytes. Basic FGF and PDGF are known to stimulate their proliferation and delay their differentiation. Lack or excess of retinoic acid (RA) has been known for a long time to alter brain development suggesting that this compound is involved in normal brain development. Here we report that RA partially inhibits both the proliferation and the differentiation of oligodendrocyte precursor cells. It also down-regulates the mitogenic effect of bFGF on these cells while keeping them in an immature stage. RA is more effective than bFGF in inhibiting myelin basic protein mRNA expression in these cells, and like bFGF, it preserves their bipotential character. RA nuclear receptors RAR-alpha and their transcripts are expressed in oligodendrocyte precursor cells as seen by Western blot, Northern blot and in situ hybridization. The expression of RAR-alpha transcripts is stimulated transiently by RA alone or associated to bFGF. The expression of RAR-beta transcripts is not constitutive and is induced by RA alone or associated to bFGF and to a lesser extent by bFGF alone. These results suggest that retinoids participate in the control of the development of glial cells of the oligodendrocyte lineage.

  2. Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration

    PubMed Central

    Herrera, María I.; Kölliker-Frers, Rodolfo; Barreto, George; Blanco, Eduardo; Capani, Francisco

    2016-01-01

    Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells. PMID:27199733

  3. Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration.

    PubMed

    Herrera, María I; Kölliker-Frers, Rodolfo; Barreto, George; Blanco, Eduardo; Capani, Francisco

    2016-01-01

    Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells.

  4. PREDICTING SIGNIFICANCE OF UNKNOWN VARIANTS IN GLIAL TUMORS THROUGH SUB-CLASS ENRICHMENT.

    PubMed

    Fichtenholtz, Alex M; Camarda, Nicholas D; Neumann, Eric K

    2016-01-01

    Glial tumors have been heavily studied and sequenced, leading to scores of findings about altered genes. This explosion in knowledge has not been matched with clinical success, but efforts to understand the synergies between drivers of glial tumors may alleviate the situation. We present a novel molecular classification system that captures the combinatorial nature of relationships between alterations in these diseases. We use this classification to mine for enrichment of variants of unknown significance, and demonstrate a method for segregating unknown variants with functional importance from passengers and SNPs.

  5. Antimicrobial peptide precursor structures suggest effective production strategies.

    PubMed

    Vassilevski, Alexander A; Kozlov, Sergey A; Grishin, Eugene V

    2008-01-01

    Antimicrobial peptides (AMPs) constitute a diverse group of compounds that serve a common goal that is host organism defense from infection. Due to their antimicrobial properties, these molecules attract practical interest as potential antibiotics for medical and veterinary use as well as enhancers of plant disease resistance for agriculture. Broad AMP utilization is restricted by the expensiveness of their production using conventional chemical synthesis. For this reason, a number of chimeric genes have been developed for recombinant AMP production in prokaryotes. However, recombinant peptide instability and/or high toxicity to host cells dramatically reduce the yields. In this paper, we review patented strategies of fusion protein design for AMP production. In several cases, the proposed strategies clearly mimic the organization of natural AMP precursor proteins. We describe the main principals of natural AMP precursor organization and fusion constructs adopted and/or artificially designed by man.

  6. The absorption spectra of carbonates and their precursors.

    NASA Astrophysics Data System (ADS)

    Koike, C.; Chihara, H.; Suto, H.

    The carbonates calcite and dolomite have been discovered in the dust shells of evolved stars (Kemper et al. 2002) and young proto stars (Ceccarelli et al. 2002). The mechanism for carbonate formation with a aqueous or non-aqueous process were discussed in their papers. These processes have not yet been reproduced in a laboratory experiment. First of all, we measured the mass absorption spectra of varous carbonates were measured in the mid- and far-infrared region. These spectra show very strong and broad peaks in the far-infrared region. The calcite and dolomite have peaks at about 92 microns and 63 microns, respectively. The alternative process of carbonates has not yet been clear. We investigate the alternative process measuring the spectra of the precursors of carbonates. We will report the preliminary results and discuss about the alternative process comparing the measured spectra of the precursors with the observation.

  7. Robotic Precursor Missions for Mars Habitats

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terry; Pirjanian, Paolo; Schenker, Paul S.; Trebi-Ollennu, Ashitey; Das, Hari; Joshi, Sajay

    2000-01-01

    Infrastructure support for robotic colonies, manned Mars habitat, and/or robotic exploration of planetary surfaces will need to rely on the field deployment of multiple robust robots. This support includes such tasks as the deployment and servicing of power systems and ISRU generators, construction of beaconed roadways, and the site preparation and deployment of manned habitat modules. The current level of autonomy of planetary rovers such as Sojourner will need to be greatly enhanced for these types of operations. In addition, single robotic platforms will not be capable of complicated construction scenarios. Precursor robotic missions to Mars that involve teams of multiple cooperating robots to accomplish some of these tasks is a cost effective solution to the possible long timeline necessary for the deployment of a manned habitat. Ongoing work at JPL under the Mars Outpost Program in the area of robot colonies is investigating many of the technology developments necessary for such an ambitious undertaking. Some of the issues that are being addressed include behavior-based control systems for multiple cooperating robots (CAMPOUT), development of autonomous robotic systems for the rescue/repair of trapped or disabled robots, and the design and development of robotic platforms for construction tasks such as material transport and surface clearing.

  8. Robotic Precursor Missions for Mars Habitats

    NASA Astrophysics Data System (ADS)

    Huntsberger, Terry; Pirjanian, Paolo; Schenker, Paul S.; Trebi-Ollennu, Ashitey; Das, Hari; Joshi, Sajay

    2000-07-01

    Infrastructure support for robotic colonies, manned Mars habitat, and/or robotic exploration of planetary surfaces will need to rely on the field deployment of multiple robust robots. This support includes such tasks as the deployment and servicing of power systems and ISRU generators, construction of beaconed roadways, and the site preparation and deployment of manned habitat modules. The current level of autonomy of planetary rovers such as Sojourner will need to be greatly enhanced for these types of operations. In addition, single robotic platforms will not be capable of complicated construction scenarios. Precursor robotic missions to Mars that involve teams of multiple cooperating robots to accomplish some of these tasks is a cost effective solution to the possible long timeline necessary for the deployment of a manned habitat. Ongoing work at JPL under the Mars Outpost Program in the area of robot colonies is investigating many of the technology developments necessary for such an ambitious undertaking. Some of the issues that are being addressed include behavior-based control systems for multiple cooperating robots (CAMPOUT), development of autonomous robotic systems for the rescue/repair of trapped or disabled robots, and the design and development of robotic platforms for construction tasks such as material transport and surface clearing.

  9. Annealing of aromatic polyimide precursors

    NASA Technical Reports Server (NTRS)

    Wakelyn, N. T.

    1975-01-01

    A study has been made of the thermal behavior of polyimide precursors: an isomeric pair of crystals of the complex formed by p-phenylenediamine with the separated isomers of the di-isopropyl ester of pyromellitic acid. Specimens of this material were isothermally annealed in the temperature range 120 C to 170 C for periods of time up to 1 week. Although this temperature range is well below that customarily used for imidizations, the working hypothesis was that it would be more likely that a polymer embodying at least part of the precursor structure could be formed if the molecular motion was minimized to that actually required for the formation of the imide linkage. The progress of the annealing was followed by: infrared spectroscopy, differential thermal analysis, powder X-ray diffraction, and thermal gravimetric analysis. Single crystal X-ray analysis of the meta monomer yields a structure of chains of alternating acid and base and suggests that this monomer is amenable to polymerization with a minimum of geometrical disruption.

  10. [Electron microscopic and cytochemical research on the function of the glial cells in a focus of local cortical destruction].

    PubMed

    Kleshchinov, V N; Koĭdan, E I; Kolomeets, N S

    1986-08-01

    The activity of DNA-RNA-protein synthesizing system of some glial cells was studied using electron cytochemical method for determination of chromatin state and RNA-particles. A dependence of functional state of satellite glial cells (oligodendroglia and astroglia) on the tinctorial neuron state (hyper- and hypochromic scale) was shown. The functional state of interfascicular oligodendroglial cells has been characterized.

  11. Age-Dependent Netrin-1 Signaling Regulates NG2+ Glial Cell Spatial Homeostasis in Normal Adult Gray Matter.

    PubMed

    Birey, Fikri; Aguirre, Adan

    2015-04-29

    Neuron-glial antigen 2-positive (NG2(+)) glial cells are the most proliferative glia type in the adult CNS, and their tile-like arrangement in adult gray matter is under tight regulation. However, little is known about the cues that govern this unique distribution. To this end, using a NG2(+) glial cell ablation model in mice, we examined the repopulation dynamics of NG2(+) glial cells in the mature and aged mice gray matter. We found that some resident NG2(+) glial cells that escaped depletion rapidly enter the cell cycle to repopulate the cortex with altered spatial distribution. We reveal that netrin-1 signaling is involved in the NG2(+) glial cell early proliferative, late repopulation, and distribution response after ablation in the gray matter. However, ablation of NG2(+) glial cell in older animals failed to stimulate a similar repopulation response, possibly because of a decrease in the sensitivity to netrin-1. Our findings indicate that endogenous netrin-1 plays a role in NG2(+) glial cell homeostasis that is distinct from its role in myelination.

  12. GlialCAM, a CLC-2 Cl(-) channel subunit, activates the slow gate of CLC chloride channels.

    PubMed

    Jeworutzki, Elena; Lagostena, Laura; Elorza-Vidal, Xabier; López-Hernández, Tania; Estévez, Raúl; Pusch, Michael

    2014-09-02

    GlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl(-) channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and thus studied GlialCAM interaction with CLC channels to investigate the mechanism of functional activation. GlialCAM slowed deactivation kinetics of CLC-Ka/barttin channels and increased CLC-0 currents opening the common gate and slowing its deactivation. No functional effect was seen for common gate deficient CLC-0 mutants. Similarly, GlialCAM targets the common gate deficient CLC-2 mutant E211V/H816A to cell contacts, without altering its function. Thus, GlialCAM is able to interact with all CLC channels tested, targeting them to cell junctions and activating them by stabilizing the open configuration of the common gate. These results are important to better understand the physiological role of GlialCAM/CLC-2 interaction.

  13. The involvement of MAP kinases JNK and p38 in photodynamic injury of crayfish neurons and glial cells

    NASA Astrophysics Data System (ADS)

    Petin, Y. O.; Bibov, M. Y.; Uzdensky, A. B.

    2007-05-01

    The role of JNK and p38 MAP kinases in functional inactivation and necrosis of mechanoreceptor neurons as well as necrosis, apoptosis and proliferation of satellite glial cells induced by photodynamic treatment (10 -7 M Photosens, 30 min incubation, 670 nm laser irradiation at 0.4 W/cm2) in the isolated crayfish stretch receptor was studied using specific inhibitors SP600125 and SB202190, respectively. SP600125 enhanced PDT-induced apoptosis of photosensitized glial cells but did not influence PDT-induced changes in neuronal activity, density of glial nuclei around neuron body, and necrosis of receptor neurons and glial cells. SB202190 did not influence neuron activity and survival as well but reduced PDT-induced necrosis but not apoptosis of glial cells. Therefore, both MAP kinases influenced glial cells but not neurons. JNK protected glial cells from PDT-induced apoptosis but did not influence necrosis and proliferation of these cells. In contrast, p38 did not influence apoptosis but contributed into PDT-induced necrosis of glial cells and PDT-induced gliosis. These MAP kinase inhibitors may be used for modulation of photodynamic therapy of brain tumors.

  14. Multiphoton microscopy of cleared mouse organs

    NASA Astrophysics Data System (ADS)

    Parra, Sonia G.; Chia, Thomas H.; Zinter, Joseph P.; Levene, Michael J.

    2010-05-01

    Typical imaging depths with multiphoton microscopy (MPM) are limited to less than 300 μm in many tissues due to light scattering. Optical clearing significantly reduces light scattering by replacing water in the organ tissue with a fluid having a similar index of refraction to that of proteins. We demonstrate MPM of intact, fixed, cleared mouse organs with penetration depths and fields of view in excess of 2 mm. MPM enables the creation of large 3-D data sets with flexibility in pixel format and ready access to intrinsic fluorescence and second-harmonic generation. We present high-resolution images and 3-D image stacks of the brain, small intestine, large intestine, kidney, lung, and testicle with image sizes as large as 4096×4096 pixels.

  15. Connexin43 and connexin47 alterations after neural precursor cells transplantation in experimental autoimmune encephalomyelitis.

    PubMed

    Theotokis, Paschalis; Kleopa, Kleopas A; Touloumi, Olga; Lagoudaki, Roza; Lourbopoulos, Athanasios; Nousiopoulou, Evangelia; Kesidou, Evangelia; Poulatsidou, Kyriaki-Nepheli; Dardiotis, Efthimios; Hadjigeorgiou, Georgios; Karacostas, Dimitris; Cifuentes-Diaz, Carmen; Irinopoulou, Theano; Grigoriadis, Nikolaos

    2015-10-01

    Exogenous transplanted neural precursor cells (NPCs) exhibit miscellaneous immune-modulatory effects in models of autoimmune demyelination. However, the regional interactions of NPCs with the host brain tissue in remissive inflammatory events have not been adequately studied. In this study we used the chronic MOG-induced Experimental Autoimmune Encephalomyelitis (EAE) model in C57BL/six mice. Based on previous data, we focused on neuropathology at Day 50 post-induction (D50) and studied the expression of connexin43 (Cx43) and Cx47, two of the main glial gap junction (GJ) proteins, in relation to the intraventricular transplantation of GFP(+) NPCs and their integration with the host tissue. By D50, NPCs had migrated intraparenchymally and were found in the corpus callosum at the level of the lateral ventricles and hippocampus. The majority of GFP(+) cells differentiated with simple or ramified processes expressing mainly markers of mature GLIA (GFAP and NogoA) and significantly less of precursor glial cells. GFP(+) NPCs expressed connexins and formed GJs around the hippocampus more than lateral ventricles. The presence of NPCs did not alter the increase in Cx43 GJ plaques at D50 EAE, but prevented the reduction of oligodendrocytic Cx47, increased the number of oligodendrocytes, local Cx47 levels and Cx47 GJ plaques per cell. These findings suggest that transplanted NPCs may have multiple effects in demyelinating pathology, including differentiation and direct integration into the panglial syncytium, as well as amelioration of oligodendrocyte GJ loss, increasing the supply of potent myelinating cells to the demyelinated tissue.

  16. Expression of a set of glial cell-specific markers in the Drosophila embryonic central nervous system.

    PubMed

    Ahn, Hui Jeong; Jeon, Sang-Hak; Kim, Sang Hee

    2014-06-01

    The types of glia in the central nervous system (CNS) of the Drosophila embryo include longitudinal glia (LG), cell body glia (CBG), and peripheral glia (PG). Transcription factors, such as glial cell missing and reverse polarity, are well-established general glial cell markers. Only a few glial cell-specific markers have been identified in the Drosophila embryonic CNS, thus far. In the present study, we employed the glial cell-specific markers for LG (vir-1/CG5453 and CG31235), CBG (fabp/CG6783 and CG11902), and PG (CG2310 and moody/CG4322), and comprehensively analyzed their expression patterns, during the embryonic CNS development. Our study validated the specificity of a set of glial markers, and further revealed their spatio-temporal expression patterns, which will aid in the understanding of the developmental lineage, and investigating their role in the development and homeostasis of the Drosophila CNS in vivo.

  17. Shiga toxin-2 enhances heat-shock-induced apoptotic cell death in cultured and primary glial cells.

    PubMed

    Sugimoto, Naotoshi; Toma, Tomoko; Shimizu, Masaki; Kuroda, Mondo; Wada, Taizo; Yachie, Akihiro

    2014-10-01

    The blood-brain barrier (BBB) selectively controls the homeostasis of the central nervous system (CNS) environment using specific structural and biochemical features of the endothelial cells, pericytes, and glial limitans. Glial cells, which represent the cellular components of the mature BBB, are the most numerous cells in the brain and are indispensable for neuronal functioning. We investigated the effects of Shiga toxin on glial cells in vitro. Shiga toxin failed to inhibit cell proliferation but attenuated expression of heat shock protein 70, which is one of the chaperone proteins, in cultured and primary glial cells. Furthermore, the combination of Shiga toxin and a heat shock procedure induced cell apoptosis and decreased cell proliferation in both cells. Thus, we speculate that glial cell death in response to the combination of Shiga toxin and heat shock might weaken the BBB and induce central nervous system complications.

  18. 77 FR 12896 - Self-Regulatory Organizations; Midwest Clearing Corporation; Order Cancelling Clearing Agency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Midwest Clearing Corporation; Order Cancelling Clearing Agency....'' \\11\\ \\11\\ CHX 2009 Letter. Section 19(a)(3) of the Act provides that in the event any self-...

  19. 77 FR 12896 - Self-Regulatory Organizations; Pacific Clearing Corporation; Order Cancelling Clearing Agency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Pacific Clearing Corporation; Order Cancelling Clearing Agency..., 2006), 72 FR 814 (Jan. 8, 2007). Section 19(a)(3) of the Act \\14\\ provides that in the event any...

  20. Chemical cleaning clears San Miguel's boiler tubes

    SciTech Connect

    Buecker, B.; Wofford, J. ); Magel, R. )

    1994-06-01

    This article describes chemical cleaning of the San Miguel Electric Cooperative (SMEC) boiler, an opposed-fired, natural circulation, reheat unit. At maximum continuous rating, steam flow is 3,054,000 lb/hr at a pressure of 2,925 psig. The superheater and reheater design temperatures are both 1,005 F. Boiler volume is 69,000 gallons. The Unit 1 boiler had not been cleaned since 1980, its original start-up date. Tube sample analyses indicated deposit densities ranging from 12 to 26 grams/ft[sup 2]. Utility boiler tubes will, over time, accumulate an internal layer of iron oxides and other deposits that inhibit flow and heat transfer, even with well-controlled water chemistry. Tube deposits can speed up corrosion, cause tube overheating, and be a precursor to tube failure. Deposits can influence such phenomena as phosphate hideout, and reduce boiler efficiency. For many utility boilers, a periodic cleaning is necessary to remove internal deposits before they can cause serious problems. Regardless of the benefits, chemical cleanings often make plant managers, engineers, and operators anxious because the process has been known to cause equipment damage or extend the length of an outage.

  1. Molecular and polymeric ceramic precursors

    SciTech Connect

    Sneddon, L.G.

    1991-08-01

    The development of new methods for the production of complex materials is one of the most important problems in modern solid state chemistry and materials science. This project is attempting to apply the synthetic principles which have evolved inorganic and organometallic chemistry to the production of technologically important non-oxide ceramics, such as boron nitride, boron carbide and metal borides. Our recent work has now resulted in the production of new polymer systems, including poly(B-vinylborazine), polyvinylpentaborane and polyborazylene, that have proven to be high yield precursors to boron-based ceramic materials. Current work is now directed toward the synthesis of new types of molecular and polymeric boron-containing species and on exploration of the solid state properties of the ceramics that have been produced in these studies.

  2. Store-operated calcium entry is essential for glial calcium signalling in CNS white matter.

    PubMed

    Papanikolaou, M; Lewis, A; Butt, A M

    2017-02-28

    'Calcium signalling' is the ubiquitous response of glial cells to multiple extracellular stimuli. The primary mechanism of glial calcium signalling is by release of calcium from intracellular stores of the endoplasmic reticulum (ER). Replenishment of ER Ca(2+) stores relies on store-operated calcium entry (SOCE). However, despite the importance of calcium signalling in glial cells, little is known about their mechanisms of SOCE. Here, we investigated SOCE in glia of the mouse optic nerve, a typical CNS white matter tract that comprises bundles of myelinated axons and the oligodendrocytes and astrocytes that support them. Using quantitative RT-PCR, we identified Orai1 channels, both Stim1 and Stim2, and the transient receptor potential M3 channel (TRPM3) as the primary channels for SOCE in the optic nerve, and their expression in both astrocytes and oligodendrocytes was demonstrated by immunolabelling of optic nerve sections and cultures. The functional importance of SOCE was demonstrated by fluo-4 calcium imaging on isolated intact optic nerves and optic nerve cultures. Removal of extracellular calcium ([Ca(2+)]o) resulted in a marked depletion of glial cytosolic calcium ([Ca(2+)]i), which recovered rapidly on restoration of [Ca(2+)]o via SOCE. 2-aminoethoxydiphenylborane (2APB) significantly decreased SOCE and severely attenuated ATP-mediated calcium signalling. The results provide evidence that Orai/Stim and TRPM3 are important components of the 'calcium toolkit' that underpins SOCE and the sustainability of calcium signalling in white matter glia.

  3. Maintenance of Fura-2 fluorescence in glial cells and neurons of the leech central nervous system.

    PubMed

    Munsch, T; Deitmer, J W

    1995-04-01

    Identified glial cells and neurones of the leech central nervous system (CNS) were injected iontophoretically with the calcium indicator dye Fura-2 to measure intracellular Ca2+, while simultaneously recording the membrane potential using a double-barrelled theta-type microelectrode. Both glial cells and neurones responded with Ni(2+)-sensitive Ca2+ transients upon membrane depolarization, indicating Ca2+ influx through voltage-gated Ca2+ channels. In contrast to neurones, the glial cells showed a rapid loss of fluorescence with a half-time of 6.3 +/- 1.8 min (n = 6) after dye injection. Both kinetics and amplitudes of the stimulus-induced Ca2+ transients were affected by this rapid dye loss. The anion exchange inhibitor probenicid (2 mM) significantly reduced, but did not prevent, the loss of Fura-2 fluorescence, suggesting that some dye left the glial cell via an anion exchanger. In order to compensate this fluorescence loss, we injected Fura-2 throughout the experiment. Under this condition, similar Ca2+ transients could be elicited repeatedly for more than 1 h. In Retzius neurones single injections of Fura-2 yielded enough intracellularly trapped dye to allow measurement of intracellular Ca2+ for up to 30 min after the end of injection without large decrease in absolute fluorescence.

  4. Postnatal development of neurons, interneurons and glial cells in the substantia nigra of mice.

    PubMed

    Abe, Manami; Kimoto, Hiroki; Eto, Risa; Sasaki, Taeko; Kato, Hiroyuki; Kasahara, Jiro; Araki, Tsutomu

    2010-08-01

    We investigated postnatal alterations of neurons, interneurons and glial cells in the mouse substantia nigra using immunohistochemistry. Tyrosine hydroxylase (TH), neuronal nuclei (NeuN), parvalbumin (PV), neuronal nitric oxide synthase (nNOS), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba 1), CNPase (2',3'-cyclic nucleotide 3'-phosphodiesterase), brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) immunoreactivity were measured in 1-, 2-, 4- and 8-week-old mice. In the present study, the maturation of NeuN-immunopositive neurons preceded the production of TH in the substantia nigra during postnatal development in mice. Furthermore, the maturation of nNOS-immunopositive interneurons preceded the maturation of PV-immunopositive interneurons in the substantia nigra during postnatal development. Among astrocytes, microglia and oligodendrocytes, in contrast, the development process of oligodendrocytes is delayed in the substantia nigra. Our double-labeled immunohistochemical study suggests that the neurotrophic factors such as BDNF and GDNF secreted by GFAP-positive astrocytes may play some role in maturation of neurons, interneurons and glial cells of the substantia nigra during postnatal development in mice. Thus, our findings provide valuable information on the development processes of the substantia nigra.

  5. Myricetin and quercetin attenuate ischemic injury in glial cultures by different mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have demonstrated that polyphenols from cinnamon and green tea reduce cell swelling and mitochondrial dysfunction in C6 glial cultures following ischemic injury. We tested the protective effects of the flavonoid polyphenols, myricetin and quercetin, on key features of ischemic injury. C6 cultures...

  6. Ganglionic GFAP (+) glial Gq-GPCR signaling enhances heart functions in vivo.

    PubMed

    Xie, Alison Xiaoqiao; Lee, Jakovin J; McCarthy, Ken D

    2017-01-26

    The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein-coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein-expressing (GFAP(+)) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP(+) glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions. In this study, we investigated whether Gq-GPCR activation in GFAP(+) glia modulates the regulatory effect of the SNS on the heart; transgenic mice expressing Gq-coupled DREADD (designer receptors exclusively activated by designer drugs) (hM3Dq) selectively in GFAP(+) glia were used to address this question in vivo. We found that acute Gq-GPCR activation in peripheral GFAP(+) glia significantly accelerated heart rate and increased left ventricle contraction. Pharmacological experiments suggest that the glial-induced cardiac changes were due to Gq-GPCR activation in satellite glial cells within the sympathetic ganglion; this activation led to increased norepinephrine (NE) release and beta-1 adrenergic receptor activation within the heart. Chronic glial Gq-GPCR activation led to hypotension in female Gfap-hM3Dq mice. This study provides direct evidence that Gq-GPCR activation in peripheral GFAP(+) glia regulates cardiovascular functions in vivo.

  7. Flavonoids modulate the proliferation of Neospora caninum in glial cell primary cultures.

    PubMed

    Matos, Rosan Barbosa de; Braga-de-Souza, Suzana; Pitanga, Bruno Pena Seara; Silva, Victor Diógenes Amaral da; Jesus, Erica Etelvina Viana de; Pinheiro, Alexandre Morales; Costa, Maria de Fátima Dias; El-Bacha, Ramon dos Santos; Ribeiro, Cátia Suse de Oliveira; Costa, Silvia Lima

    2014-12-01

    Neospora caninum (Apicomplexa; Sarcocystidae) is a protozoan that causes abortion in cattle, horses, sheep, and dogs as well as neurological and dermatological diseases in dogs. In the central nervous system of dogs infected with N. caninum, cysts were detected that exhibited gliosis and meningitis. Flavonoids are polyphenolic compounds that exhibit antibacterial, antiparasitic, antifungal, and antiviral properties. In this study, we investigated the effects of flavonoids in a well-established in vitro model of N. caninum infection in glial cell cultures. Glial cells were treated individually with 10 different flavonoids, and a subset of cultures was also infected with the NC-1 strain of N. caninum. All of the flavonoids tested induced an increase in the metabolism of glial cells and many of them increased nitrite levels in cultures infected with NC-1 compared to controls and uninfected cultures. Among the flavonoids tested, 3',4'-dihydroxyflavone, 3',4',5,7-tetrahydroxyflavone (luteolin), and 3,3',4',5,6-pentahydroxyflavone (quercetin), also inhibited parasitophorous vacuole formation. Taken together, our findings show that flavonoids modulate glial cell responses, increase NO secretion, and interfere with N. caninum infection and proliferation.

  8. Satellite glial cells in situ within mammalian prevertebral ganglia express K+ channels active at rest potential.

    PubMed

    Gola, M; Niel, J P; Delmas, P; Jacquet, G

    1993-10-01

    Patch-clamp experiments were performed on satellite glial cells wrapped around sympathetic neurons in the rabbit coeliac ganglion. With the cleaning method used, the glial cells could be kept in place and were directly accessible to the patch-clamp pipettes. Whole-cell recordings showed that glial cells had almost ohmic properties. Their resting potential (-79.1 +/- 1.2 mV) was found to be very nearly the same as the K+ reversal potential and approximately 20 mV more negative than that of the neurons they encapsulated. Unitary currents from ionic channels present in the glial membrane were recorded in the cell-attached configuration with pipettes filled with various amounts of K+, Na+ and gluconate. Only K(+)-selective channels with slight inwardly rectifying properties (in the presence of 150 mM [K+]o) were detected. These channels were active (Po = 0.7-0.8) at the cell resting potential. The channel conductance, but not its opening probability, was dependent on the [K+] in the pipette. Cl(-)-selective channels (outwardly rectifying and large conductance channels) were detected in excised patches. The properties of the K+ channels (increased inward current with [K+] and detectable outward current at low [K+]) are well suited for siphoning the K+ released by active neurons.

  9. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence.

    PubMed

    Ibiza, Sales; García-Cassani, Bethania; Ribeiro, Hélder; Carvalho, Tânia; Almeida, Luís; Marques, Rute; Misic, Ana M; Bartow-McKenney, Casey; Larson, Denise M; Pavan, William J; Eberl, Gérard; Grice, Elizabeth A; Veiga-Fernandes, Henrique

    2016-07-21

    Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers. ILC3 development is thought to be programmed, but how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 in mice sense their environment and control gut defence as part of a glial–ILC3–epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate Il22 downstream of the p38 MAPK/ERK-AKT cascade and STAT3 activation. Notably, ILC3 were adjacent to neurotrophic-factor-expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88-dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired production of ILC3-derived IL-22 and a pronounced propensity towards gut inflammation and infection. Our work sheds light on a novel multi-tissue defence unit, revealing that glial cells are central hubs of neuron and innate immune regulation by neurotrophic factor signals.

  10. Inflammation-like glial response in lead-exposed immature rat brain.

    PubMed

    Struzynska, Lidia; Dabrowska-Bouta, Beata; Koza, Katarzyna; Sulkowski, Grzegorz

    2007-01-01

    Numerous studies on lead (Pb) neurotoxicity have indicated this metal to be a dangerous toxin, particularly during developmental stages of higher organisms. Astrocytes are responsible for sequestration of this metal in brain tissue. Activation of astroglia may often lead to loss of the buffering function and contribute to pathological processes. This phenomenon is accompanied by death of neuronal cells and may be connected with inflammatory events arising from the production of a wide range of cytokines and chemokines. The effects of prolonged exposure to Pb upon glial activation are examined in immature rats to investigate this potential proinflammatory effect. When analyzed at the protein level, glial activation is observed after Pb exposure, as reflected by the increased level of glial fibrillary acidic protein and S-100beta proteins in all parts of the brain examined. These changes are associated with elevation of proinflammatory cytokines. Production of interleukin (IL)-1beta and tumor necrosis factor-alpha is observed in hippocampus, and production of IL-6 is seen in forebrain. The expression of fractalkine is observed in both hippocampus and forebrain but inconsiderably in the cerebellum. In parallel with cytokine expression, signs of synaptic damage in hippocampus are seen after Pb exposure, as indicated by decreased levels of the axonal markers synapsin I and synaptophysin. Obtained results indicate chronic glial activation with coexisting inflammatory and neurodegenerative features as a new mechanism of Pb neurotoxicity in immature rat brain.

  11. Satellite glial cells in sympathetic and parasympathetic ganglia: in search of function.

    PubMed

    Hanani, Menachem

    2010-09-24

    Glial cells are established as essential for many functions of the central nervous system, and this seems to hold also for glial cells in the peripheral nervous system. The main type of glial cells in most types of peripheral ganglia - sensory, sympathetic, and parasympathetic - is satellite glial cells (SGCs). These cells usually form envelopes around single neurons, which create a distinct functional unit consisting of a neuron and its attending SGCs. This review presents the knowledge on the morphology of SGCs in sympathetic and parasympathetic ganglia, and the (limited) available information on their physiology and pharmacology. It appears that SGCs carry receptors for ATP and can thus respond to the release of this neurotransmitter by the neurons. There is evidence that SGCs have an uptake mechanism for GABA, and possibly other neurotransmitters, which enables them to control the neuronal microenvironment. Damage to post- or preganglionic nerve fibers influences both the ganglionic neurons and the SGCs. One major consequence of postganglionic nerve section is the detachment of preganglionic nerve terminals, resulting in decline of synaptic transmission. It appears that, at least in sympathetic ganglia, SGCs participate in the detachment process, and possibly in the subsequent recovery of the synaptic connections. Unlike sensory neurons, neurons in autonomic ganglia receive synaptic inputs, and SGCs are in very close contact with synaptic boutons. This places the SGCs in a position to influence synaptic transmission and information processing in autonomic ganglia, but this topic requires much further work.

  12. Comparative assessment of iridium oxide and platinum alloy wires using an in vitro glial scar assay.

    PubMed

    Ereifej, Evon S; Khan, Saida; Newaz, Golam; Zhang, Jinsheng; Auner, Gregory W; VandeVord, Pamela J

    2013-12-01

    The long-term effect of chronically implanted electrodes is the formation of a glial scar. Therefore, it is imperative to assess the biocompatibility of materials before employing them in neural electrode fabrication. Platinum alloy and iridium oxide have been identified as good candidates as neural electrode biomaterials due to their mechanical and electrical properties, however, effect of glial scar formation for these two materials is lacking. In this study, we applied a glial scarring assay to observe the cellular reactivity to platinum alloy and iridium oxide wires in order to assess the biocompatibility based on previously defined characteristics. Through real-time PCR, immunostaining and imaging techniques, we will advance the understanding of the biocompatibility of these materials. Results of this study demonstrate iridium oxide wires exhibited a more significant reactive response as compared to platinum alloy wires. Cells cultured with platinum alloy wires had less GFAP gene expression, lower average GFAP intensity, and smaller glial scar thickness. Collectively, these results indicated that platinum alloy wires were more biocompatible than the iridium oxide wires.

  13. Glial fibrillary acidic protein (GFAP) shows circadian oscillations in crayfish Procambarus clarkii putative pacemakers.

    PubMed

    Rodríguez-Muñoz, María de la Paz; Escamilla-Chimal, Elsa G

    2015-01-01

    Although several studies of glia have examined glial fibrillary acid protein (GFAP) and its relationship to the circadian rhythms of different organisms, they have not explored the daily GFAP oscillations in the putative pacemakers of the crayfish Procambarus clarkii or in other crustaceans. In this study we investigated the daily variations in GFAP concentrations in the eyestalk and brain, which are considered to be putative pacemakers in adult P. clarkii. In both structures, the glial GFAP was quantified using the indirect enzyme-linked immunosorbent assay (ELISA), and double labeling immunofluorescence was used to detect it and its co-localization with protein Period (PER), an important component of the circadian clock, in various regions of both structures. The ELISA results were analyzed using Cosinor and one-way ANOVA with Bonferroni and Scheffé's post hoc tests. The results of this analysis showed that the GFAP levels present circadian oscillations in both structures. Moreover, GFAP was localized in different structures of the eyestalk and brain; however, co-localization with PER occurred only in the lamina ganglionaris, specifically in the cartridges of the eyestalk and in some of the cluster 9 brain cells. These results suggest that as in other invertebrates and vertebrates, glial cells could be involved in the circadian system of P. clarkii; however, thus far we cannot know whether the glial cells are only effectors, participate in afferent pathways, or are part of the circadian clock.

  14. Glial scar size, inhibitor concentration, and growth of regenerating axons after spinal cord transection☆

    PubMed Central

    Zhu, Weiping; Sun, Yanping; Chen, Xuning; Feng, Shiliang

    2012-01-01

    A mathematical model has been formulated in accordance with cell chemotaxis and relevant experimental data. A three-dimensional lattice Boltzmann method was used for numerical simulation. The present study observed the effects of glial scar size and inhibitor concentration on regenerative axonal growth following spinal cord transection. The simulation test comprised two parts: (1) when release rates of growth inhibitor and promoter were constant, the effects of glial scar size on axonal growth rate were analyzed, and concentrations of inhibitor and promoters located at the moving growth cones were recorded. (2) When the glial scar size was constant, the effects of inhibitor and promoter release rates on axonal growth rate were analyzed, and inhibitor and promoter concentrations at the moving growth cones were recorded. Results demonstrated that (1) a larger glial scar and a higher release rate of inhibitor resulted in a reduced axonal growth rate. (2) The axonal growth rate depended on the ratio of inhibitor to promoter concentrations at the growth cones. When the average ratio was < 1.5, regenerating axons were able to grow and successfully contact target cells. PMID:25657689

  15. [Symptomatic glial cysts of the pineal gland: report of two cases and review of the literature].

    PubMed

    Vajtai, I; Bodosi, M; Varga, Z; Ormos, J; Vörös, E

    1995-08-27

    Referring to two individual cases, the authors review clinical, radiological and histological features of benign glial cysts of the pineal gland. Both patients were young females with aggravating headaches and with convulsions in one case. Symptoms were referable to a space-occupying cystic mass of the pineal gland. On histology, both lesions proved to be non neoplastic cysts without an epithelial lining. Their histogenesis and low growth potential were reinforced by immunohistochemical analysis of pineal antigens and proliferation markers. Glial cysts of the pineal gland are not infrequent, but symptomatic occurrences are exceptional. Most glial cysts are of dysontogenic or degenerative origin. Sometimes, however, the role of hormonal influences or paraneoplastic factors must be considered. Symptoms caused by glial cysts of the pineal gland are non-specific and radiologic imaging technics may contribute little to etiologic diagnosis. Pineal cysts are curable by surgical resection or stereotactic decompression. Whatever the diagnostic approach, emphasis must be laid on the histologic examination in order to avoid unnecessarily aggressive treatment.

  16. Improved Visualization of Neuronal Injury Following Glial Activation by Manganese Enhanced MRI

    PubMed Central

    Bade, Aditya N.; Zhou, Biyun; Epstein, Adrian A.; Gorantla, Santhi; Poluektova, Larisa Y.; Luo, Jiangtao; Gendelman, Howard E.; Boska, Michael D.; Liu, Yutong

    2013-01-01

    Research directed at anatomical, integrative and functional activities of the central nervous system (CNS) can be realized through bioimaging. A wealth of data now demonstrates the utility of magnetic resonance imaging (MRI) towards unraveling complex neural connectivity operative in health and disease. A means to improve MRI sensitivity is through contrast agents and notably manganese (Mn2+). The Mn2+ ions enter neurons through voltage-gated calcium channels and unlike other contrast agents such as gadolinium, iron oxide, iron platinum and imaging proteins, provide unique insights into brain physiology. Nonetheless, a critical question that remains is the brain target cells serving as sources for the signal of Mn2+ enhanced MRI (MEMRI). To this end, we investigated MEMRI’s abilities to detect glial (astrocyte and microglia) and neuronal activation signals following treatment with known inflammatory inducing agents. The idea is to distinguish between gliosis (glial activation) and neuronal injury for the MEMRI signal and as such use the agent as a marker for neural activity in inflammatory and degenerative disease. We now demonstrate that glial inflammation facilitates Mn2+ neuronal ion uptake. Glial Mn2+ content was not linked to its activation. MEMRI performed on mice injected intracranially with lipopolysaccharide was associated with increased neuronal activity. These results support the notion that MEMRI reflects neuronal excitotoxicity and impairment that can occur through a range of insults including neuroinflammation. We conclude that the MEMRI signal enhancement is induced by inflammation stimulating neuronal Mn2+ uptake. PMID:23729245

  17. Cinnamon Polyphenols Attenuate Neuronal Death and Glial Swelling in Ischemic Injury

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brain edema is a major complication associated with ischemic stroke and is characterized by a volumetric enlargement of the brain. Astrocyte swelling is a major component of brain edema. We investigated the protective effects of polyphenols isolated from green tea and cinnamon in C6 glial cultures s...

  18. Controlled Adhesion and Growth of Long Term Glial and Neuronal Cultures on Parylene-C

    PubMed Central

    Delivopoulos, Evangelos; Murray, Alan F.

    2011-01-01

    This paper explores the long term development of networks of glia and neurons on patterns of Parylene-C on a SiO2 substrate. We harvested glia and neurons from the Sprague-Dawley (P1–P7) rat hippocampus and utilized an established cell patterning technique in order to investigate cellular migration, over the course of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually disrupts cellular patterns that are established early during culture. This effect is not attributed to a loss of protein from the Parylene-C surface, as nitrogen levels on the substrate remain stable over 3 weeks. The inclusion of the anti-mitotic cytarabine (Ara-C) in the culture medium moderates glial division and thus, adequately preserves initial glial and neuronal conformity to underlying patterns. Neuronal apoptosis, often associated with the use of Ara-C, is mitigated by the addition of brain derived neurotrophic factor (BDNF). We believe that with the right combination of glial inhibitors and neuronal promoters, the Parylene-C based cell patterning method can generate structured, active neural networks that can be sustained and investigated over extended periods of time. To our knowledge this is the first report on the concurrent application of Ara-C and BDNF on patterned cell cultures. PMID:21966523

  19. Glial glycine transporter 1 function is essential for early postnatal survival but dispensable in adult mice.

    PubMed

    Eulenburg, Volker; Retiounskaia, Marina; Papadopoulos, Theofilos; Gomeza, Jesús; Betz, Heinrich

    2010-07-01

    The glycine transporter 1 (GlyT1) is expressed in astrocytes and selected neurons of the mammalian CNS. In newborn mice, GlyT1 is crucial for efficient termination of glycine-mediated inhibitory neurotransmission. Furthermore, GlyT1 has been implicated in the regulation of excitatory N-methyl-D-asparate (NMDA) receptors. To evaluate whether glial and neuronal GlyT1 have distinct roles at inhibitory synapses, we inactivated the GlyT1 gene cell type-specifically using mice carrying floxed GlyT1 alleles GlyT1((+)/+)). GlyT1((+)/(+)) mice expressing Cre recombinase in glial cells developed severe neuromotor deficits during the first postnatal week, which mimicked the phenotype of conventional GlyT1 knock-out mice and are consistent with glycinergic over-inhibition. In contrast, Cre-mediated inactivation of the GlyT1 gene in neuronal cells did not result in detectable motor impairment. Notably, some animals deficient for glial GlyT1 survived the first postnatal week and did not develop neuromotor deficits throughout adulthood, although GlyT1 expression was efficiently reduced. Thus, glial GlyT1 is critical for the regulation of glycine levels at inhibitory synapses only during early postnatal life.

  20. Age-dependent responses of glial cells and leptomeninges during systemic inflammation.

    PubMed

    Wu, Zhou; Tokuda, Yukie; Zhang, Xin-Wen; Nakanishi, Hiroshi

    2008-12-01

    Systemic inflammation causes the age-dependent differential glial responses, but little is known about how age influences the barrier function of leptomeninges during systemic inflammation. This study was conducted to elucidate the relationship between the glial responses and the levels of tight junction proteins, occludin and ZO-1, in adjuvant arthritis (AA) rats. In young AA rats, microglia and astrocytes localized to the proximity of the leptomeninges expressed interleukin (IL)-10 and transforming growth factor (TGF)-beta1. The level of occludin significantly increased. In middle-aged AA rats, however, glial cells expressed IL-1beta and prostaglandin E(2) (PGE(2))-synthesizing enzymes. Furthermore, occludin and ZO-1 significantly decreased, resulting in the increased permeability of leptomeninges. In the cultured leptomeningeal cells, IL-1beta and PGE(2) caused a marked loss of occludin and ZO-1, respectively. Pretreatment with IL-10 and TGF-beta1 significantly antagonized their effects. These findings establish that age strongly influences the barrier functions of the leptomeninges through the age-dependent differential glial responses during systemic inflammation.

  1. How a radial glial cell decides to become a multiciliated ependymal cell.

    PubMed

    Kyrousi, Christina; Lygerou, Zoi; Taraviras, Stavros

    2017-02-07

    The V-SVZ adult neurogenic niche is located in the wall of the lateral ventricles and contains neural stem cells, with self-renewing and differentiating ability and postmitotic multiciliated ependymal cells, an important structural and trophic component of the niche. The niche is established at postnatal stages from a subpopulation of radial glial cells, determined during embryogenesis. Radial glial cells constitute a heterogeneous population, which give rise, in addition to niche cellular components, to neurons and glial cells. The mechanisms that direct their fate commitment towards V-SVZ niche cells are largely unknown. In the present review, we discuss recent findings on the signaling networks governing fate commitment decisions of radial glial cells towards multiciliated ependymal cells. We highlight the role of two novel factors: McIdas and GemC1/Lynkeas and the molecular pathways which they activate in order to promote ependymal cell differentiation. Finally, we discuss a possible crosstalk of known signaling pathways, such as Notch, STAT3, and BMPs, for the specification of ependymal versus adult neural stem cells in the V-SVZ niche. GLIA 2017.

  2. Ganglionic GFAP+ glial Gq-GPCR signaling enhances heart functions in vivo

    PubMed Central

    Lee, Jakovin J.; McCarthy, Ken D.

    2017-01-01

    The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein–coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein–expressing (GFAP+) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP+ glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions. In this study, we investigated whether Gq-GPCR activation in GFAP+ glia modulates the regulatory effect of the SNS on the heart; transgenic mice expressing Gq-coupled DREADD (designer receptors exclusively activated by designer drugs) (hM3Dq) selectively in GFAP+ glia were used to address this question in vivo. We found that acute Gq-GPCR activation in peripheral GFAP+ glia significantly accelerated heart rate and increased left ventricle contraction. Pharmacological experiments suggest that the glial-induced cardiac changes were due to Gq-GPCR activation in satellite glial cells within the sympathetic ganglion; this activation led to increased norepinephrine (NE) release and beta-1 adrenergic receptor activation within the heart. Chronic glial Gq-GPCR activation led to hypotension in female Gfap-hM3Dq mice. This study provides direct evidence that Gq-GPCR activation in peripheral GFAP+ glia regulates cardiovascular functions in vivo. PMID:28138563

  3. Flavonoids Modulate the Proliferation of Neospora caninum in Glial Cell Primary Cultures

    PubMed Central

    Barbosa de Matos, Rosan; Braga-de-Souza, Suzana; Pena Seara Pitanga, Bruno; Amaral da Silva, Victor Diógenes; Viana de Jesus, Erica Etelvina; Morales Pinheiro, Alexandre; Dias Costa, Maria de Fátima; dos Santos El-Bacha, Ramon; de Oliveira Ribeiro, Cátia Suse

    2014-01-01

    Neospora caninum (Apicomplexa; Sarcocystidae) is a protozoan that causes abortion in cattle, horses, sheep, and dogs as well as neurological and dermatological diseases in dogs. In the central nervous system of dogs infected with N. caninum, cysts were detected that exhibited gliosis and meningitis. Flavonoids are polyphenolic compounds that exhibit antibacterial, antiparasitic, antifungal, and antiviral properties. In this study, we investigated the effects of flavonoids in a well-established in vitro model of N. caninum infection in glial cell cultures. Glial cells were treated individually with 10 different flavonoids, and a subset of cultures was also infected with the NC-1 strain of N. caninum. All of the flavonoids tested induced an increase in the metabolism of glial cells and many of them increased nitrite levels in cultures infected with NC-1 compared to controls and uninfected cultures. Among the flavonoids tested, 3',4'-dihydroxyflavone, 3',4',5,7-tetrahydroxyflavone (luteolin), and 3,3',4',5,6-pentahydroxyflavone (quercetin), also inhibited parasitophorous vacuole formation. Taken together, our findings show that flavonoids modulate glial cell responses, increase NO secretion, and interfere with N. caninum infection and proliferation. PMID:25548412

  4. The role of NO synthase isoforms in PDT-induced injury of neurons and glial cells

    NASA Astrophysics Data System (ADS)

    Kovaleva, V. D.; Berezhnaya, E. V.; Uzdensky, A. B.

    2015-03-01

    Nitric oxide (NO) is an important second messenger, involved in the implementation of various cell functions. It regulates various physiological and pathological processes such as neurotransmission, cell responses to stress, and neurodegeneration. NO synthase is a family of enzymes that synthesize NO from L-arginine. The activity of different NOS isoforms depends both on endogenous and exogenous factors. In particular, it is modulated by oxidative stress, induced by photodynamic therapy (PDT). We have studied the possible role of NOS in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Antinecrotic and proapoptotic effects of NO on the glial cells were found using inhibitory analysis. We have shown the role of inducible NO synthase in photoinduced apoptosis and involvement of neuronal NO synthase in photoinduced necrosis of glial cells in the isolated crayfish stretch receptor. The activation of NO synthase was evaluated using NADPH-diaphorase histochemistry, a marker of neurons expressing the enzyme. The activation of NO synthase in the isolated crayfish stretch receptor was evaluated as a function of time after PDT. Photodynamic treatment induced transient increase in NO synthase activity and then slowly inhibited this enzyme.

  5. Modification of potassium movement through the retina of the drone (Apis mellifera male) by glial uptake.

    PubMed Central

    Coles, J A; Orkand, R K

    1983-01-01

    Intracellular recordings were made in photoreceptors and glial cells (outer pigment cells) of the superfused cut head of the honey-bee drone (Apis mellifera male). When the [K+] in the superfusate was abruptly increased from 3.2 mM to 17.9 mM both photoreceptors and glial cells depolarized. The time course of the depolarization of the photoreceptors was slower with increasing depth from the surface. Half time of depolarization was plotted against depth: this graph was compatible with the arrival of K+ being exclusively by diffusion through the extracellular clefts. However, as we then showed, this interpretation is inadequate. The time course of depolarization of the glial cells was almost the same at all depths. This indicates that they are electrically coupled. Consequently, current-mediated K+ flux (spatial buffering) through glial cells will contribute to the transport of K+ through the tissue: K+ ions enter the glial syncytium in the region of high external potassium concentration, [K+]0, and an equivalent quantity of K+ ions leave in regions of low [K+]0. Intracellular K+ activity (aiK) was measured with double-barrelled K+-sensitive micro-electrodes in slices of retina superfused on both faces. When [K+] in the superfusate was increased from 7.5 mM to 17.9 mM an increase in aiK was observed in glial cells at all depths in the slice (initial rate 1.7 mM min-1, S.E. of the mean = 0.2 mM min-1), but there was little increase in the photoreceptors (0.3 +/- 0.2 mM min-1). The increase in aiK in glial cells near the centre of the slice could not have been caused by spatial buffering; it presumably resulted from net uptake. We conclude that when [K+] is increased at the surface of this tissue, the build up of K+ in the extracellular clefts depends on extracellular diffusion, spatial buffering and net uptake. The latter two processes, which have opposing effects, involve about 10 times as much K+ as the first. This is in rough agreement with less direct experiments

  6. Amyloid precursor protein in Drosophila glia regulates sleep and genes involved in glutamate recycling.

    PubMed

    Farca Luna, Abud Jose; Perier, Magali; Seugnet, Laurent

    2017-03-17

    The Amyloid Precursor Protein (App) plays a crucial role in Alzheimer disease (AD) via the production and deposition of toxic β-amyloid peptides. App is heavily expressed in neurons where the vast majority of studies investigating its function have been carried out, while almost nothing is known about its function in glia, where it is also expressed, and can potentially participate in the regulation of neuronal physiology. In this report, we investigated whether Appl, the Drosophila homolog of App, could influence sleep-wake regulation when its function is manipulated in glial cells. Appl inhibition in astrocyte-like and cortex glia resulted in higher sleep amounts and longer sleep bout duration during the night, while overexpression had the opposite effect. These sleep phenotypes were not the result of developmental defects, and were correlated with changes in expression in Glutamine Synthetase (GS) in astrocyte-like glia, and in changes in the gap-junction component innexin2 in cortex glia. Downregulating both GS and innexin2, but not either one individually, resulted in higher sleep amounts, similarly to Appl inhibition. Consistent with these results the expression of GS and innexin2 are increased following sleep deprivation indicating that these two genes are dynamically linked to vigilance states. Interestingly, the reduction of GS expression and the sleep phenotype observed upon Appl inhibition could be rescued by increasing the expression of the glutamate transporter dEaat1. In contrast, reducing dEaat1 expression severely disrupted sleep. These results associate glutamate recycling, sleep and a glial function for the App family proteins.StatementThe Amyloid Precursor Protein (App) has been intensively studied for its implication in Alzheimer Disease (AD). The attributed functions of App are linked to the physiology and cellular biology of neurons where the protein is predominantly expressed. Consequences on glia in AD are generally thought to be secondary

  7. ClearedLeavesDB: an online database of cleared plant leaf images

    PubMed Central

    2014-01-01

    Background Leaf vein networks are critical to both the structure and function of leaves. A growing body of recent work has linked leaf vein network structure to the physiology, ecology and evolution of land plants. In the process, multiple institutions and individual researchers have assembled collections of cleared leaf specimens in which vascular bundles (veins) are rendered visible. In an effort to facilitate analysis and digitally preserve these specimens, high-resolution images are usually created, either of entire leaves or of magnified leaf subsections. In a few cases, collections of digital images of cleared leaves are available for use online. However, these collections do not share a common platform nor is there a means to digitally archive cleared leaf images held by individual researchers (in addition to those held by institutions). Hence, there is a growing need for a digital archive that enables online viewing, sharing and disseminating of cleared leaf image collections held by both institutions and individual researchers. Description The Cleared Leaf Image Database (ClearedLeavesDB), is an online web-based resource for a community of researchers to contribute, access and share cleared leaf images. ClearedLeavesDB leverages resources of large-scale, curated collections while enabling the aggregation of small-scale collections within the same online platform. ClearedLeavesDB is built on Drupal, an open source content management platform. It allows plant biologists to store leaf images online with corresponding meta-data, share image collections with a user community and discuss images and collections via a common forum. We provide tools to upload processed images and results to the database via a web services client application that can be downloaded from the database. Conclusions We developed ClearedLeavesDB, a database focusing on cleared leaf images that combines interactions between users and data via an intuitive web interface. The web interface

  8. Nitrous oxide flux following tropical land clearing

    NASA Technical Reports Server (NTRS)

    Luizao, Flavio; Luizao, Regina; Matson, Pamela; Livingston, Gerald; Vitousek, Peter

    1989-01-01

    The importance of seasonal cycles of N2O flux from tropical ecosystems and the possibility that tropical deforestation could contribute to the ongoing global increase in N2O concentrations were assessed by measuring N2O flux from forest, cleared land, and pasture over an annual cycle in the central Amazon. A pasture that had been converted from tropical forest had threefold greater annual N2O flux than a paired forest site; similar results were obtained in spot measurements in other pastures. If these results are general, such tropical pastures represent a globally significant source of increased N2O.

  9. PLANETARY CHAOTIC ZONE CLEARING: DESTINATIONS AND TIMESCALES

    SciTech Connect

    Morrison, Sarah; Malhotra, Renu

    2015-01-20

    We investigate the orbital evolution of particles in a planet's chaotic zone to determine their final destinations and their timescales of clearing. There are four possible final states of chaotic particles: collision with the planet, collision with the star, escape, or bounded but non-collision orbits. In our investigations, within the framework of the planar circular restricted three body problem for planet-star mass ratio μ in the range 10{sup –9} to 10{sup –1.5}, we find no particles hitting the star. The relative frequencies of escape and collision with the planet are not scale-free, as they depend upon the size of the planet. For planet radius R{sub p} ≥ 0.001 R{sub H} where R{sub H} is the planet's Hill radius, we find that most chaotic zone particles collide with the planet for μ ≲ 10{sup –5}; particle scattering to large distances is significant only for higher mass planets. For fixed ratio R{sub p} /R{sub H} , the particle clearing timescale, T {sub cl}, has a broken power-law dependence on μ. A shallower power law, T {sub cl} ∼ μ{sup –1/3}, prevails at small μ where particles are cleared primarily by collisions with the planet; a steeper power law, T {sub cl} ∼ μ{sup –3/2}, prevails at larger μ where scattering dominates the particle loss. In the limit of vanishing planet radius, we find T {sub cl} ≈ 0.024 μ{sup –3/2}. The interior and exterior boundaries of the annular zone in which chaotic particles are cleared are increasingly asymmetric about the planet's orbit for larger planet masses; the inner boundary coincides well with the classical first order resonance overlap zone, Δa {sub cl,} {sub int} ≅ 1.2 μ{sup 0.28} a{sub p} ; the outer boundary is better described by Δa {sub cl,} {sub ext} ≅ 1.7 μ{sup 0.31} a{sub p} , where a{sub p} is the planet-star separation.

  10. Leucine-nitrogen metabolism in the brain of conscious rats: its role as a nitrogen carrier in glutamate synthesis in glial and neuronal metabolic compartments.

    PubMed

    Sakai, Ryosei; Cohen, David M; Henry, Joseph F; Burrin, Douglas G; Reeds, Peter J

    2004-02-01

    The source of nitrogen (N) for the de novo synthesis of brain glutamate, glutamine and GABA remains controversial. Because leucine is readily transported into the brain and the brain contains high activities of branched-chain aminotransferase (BCAT), we hypothesized that leucine is the predominant N-precursor for brain glutamate synthesis. Conscious and unstressed rats administered with [U-13C] and/or [15N]leucine as additions to the diet were killed at 0-9 h of continuous feeding. Plasma and brain leucine equilibrated rapidly and the brain leucine-N turnover was more than 100%/min. The isotopic dilution of [U-13C]leucine (brain/plasma ratio 0.61 +/- 0.06) and [15N]leucine (0.23 +/- 0.06) differed markedly, suggesting that 15% of cerebral leucine-N turnover derived from proteolysis and 62% from leucine synthesis via reverse transamination. The rate of glutamate synthesis from leucine was 5 micro mol/g/h and at least 50% of glutamate-N originally derived from leucine. The enrichment of [5-15N]glutamine was higher than [15N]ammonia in the brain, indicating glial ammonia generation from leucine via glutamate. The enrichment of [15N]GABA, [15N]aspartate, [15N]glutamate greater than [2-15N]glutamine suggests direct incorporation of leucine-N into both glial and neuronal glutamate. These findings provide a new insight for the role of leucine as N-carrier from the plasma pool and within the cerebral compartments.

  11. Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.

    PubMed

    Bye, Nicole; Christie, Kimberly J; Turbic, Alisa; Basrai, Harleen S; Turnley, Ann M

    2016-05-01

    Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4 weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35 days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury.

  12. Analysis of Amyloid Precursor Protein Function in Drosophila melanogaster

    PubMed Central

    Cassar, Marlène; Kretzschmar, Doris

    2016-01-01

    The Amyloid precursor protein (APP) has mainly been investigated in connection with its role in Alzheimer’s Disease (AD) due to its cleavage resulting in the production of the Aβ peptides that accumulate in the plaques characteristic for this disease. However, APP is an evolutionary conserved protein that is not only found in humans but also in many other species, including Drosophila, suggesting an important physiological function. Besides Aβ, several other fragments are produced by the cleavage of APP; large secreted fragments derived from the N-terminus and a small intracellular C-terminal fragment. Although these fragments have received much less attention than Aβ, a picture about their function is finally emerging. In contrast to mammals, which express three APP family members, Drosophila expresses only one APP protein called APP-like or APPL. Therefore APPL functions can be studied in flies without the complication that other APP family members may have redundant functions. Flies lacking APPL are viable but show defects in neuronal outgrowth in the central and peripheral nervous system (PNS) in addition to synaptic changes. Furthermore, APPL has been connected with axonal transport functions. In the adult nervous system, APPL, and more specifically its secreted fragments, can protect neurons from degeneration. APPL cleavage also prevents glial death. Lastly, APPL was found to be involved in behavioral deficits and in regulating sleep/activity patterns. This review, will describe the role of APPL in neuronal development and maintenance and briefly touch on its emerging function in circadian rhythms while an accompanying review will focus on its role in learning and memory formation. PMID:27507933

  13. Stress proteins and glial cell functions during chronic aluminium exposures: protective role of curcumin.

    PubMed

    Sood, Pooja Khanna; Nahar, Uma; Nehru, Bimla

    2012-03-01

    Involved in the ongoing debate is the speculation that aluminium is somehow toxic for neurons. Glial cells cope up to protect neurons from this toxic insult by maintaining the glutathione homeostasis. Of late newer and newer roles of glial cells have been depicted. The present work looks into the other regulatory mechanisms that show the glial cells response to pro-oxidant effects of aluminium exposure. In the present investigation we have evaluated the inflammatory responses of the glial cells as well as HSP70-induction during aluminium exposure. Further, the protective role of curcumin is also evaluated. Aluminium was administered by oral gavage at a dose level of 100 mg/kg b.wt/day for a period of 8 weeks. Curcumin was administered i.p. at a dose of 50 mg/kg b.wt./day on alternate days. Enhanced gene and protein expression of HSP70 in the glial fractions of the aluminium exposed animals as compared to the corresponding neuronal population. Aluminium exposure resulted in a significant increase in the NF-κB and TNF-α expression suggesting inflammatory responses. In the conjunctive treatment group of aluminium and curcumin exposure marked reduction in the gene and protein expression of NF-κB and TNF-α was observed. This was further reflected in histopathological studies showing no evidence of inflammation in conjunctive group as compared to aluminium treatment. From the present study, it can be concluded that curcumin has a potential anti-inflammatory action and can be exploited in other toxicological conditions also.

  14. Glial cell response to 3,4-(+/-)-methylenedioxymethamphetamine and its metabolites.

    PubMed

    Herndon, Joseph M; Cholanians, Aram B; Lau, Serrine S; Monks, Terrence J

    2014-03-01

    3,4-(±)-Methylenedioxymethamphetamine (MDMA) and 3,4-(±)-methylenedioxyamphetamine (MDA), a primary metabolite of MDMA, are phenylethylamine derivatives that cause serotonergic neurotoxicity. Although several phenylethylamine derivatives activate microglia, little is known about the effects of MDMA on glial cells, and evidence of MDMA-induced microglial activation remains ambiguous. We initially determined microglial occupancy status of the parietal cortex in rats at various time points following a single neurotoxic dose of MDMA (20mg/kg, SC). A biphasic microglial response to MDMA was observed, with peak microglial occupancy occurring 12- and 72-h post-MDMA administration. Because direct injection of MDMA into the brain does not produce neurotoxicity, the glial response to MDMA metabolites was subsequently examined in vivo and in vitro. Rats were treated with MDA (20mg/kg, SC) followed by ex vivo biopsy culture to determine the activation of quiescent microglia. A reactive microglial response was observed 72 h after MDA administration that subsided by 7 days. In contrast, intracerebroventricular (ICV) administration of MDA failed to produce a microglial response. However, thioether metabolites of MDA derived from α-methyldopamine (α-MeDA) elicited a robust microglial response following icv injection. We subsequently determined the direct effects of various MDMA metabolites on primary cultures of E18 hippocampal mixed glial and neuronal cells. 5-(Glutathion-S-yl)-α-MeDA, 2,5-bis-(glutathion-S-yl)-α-MeDA, and 5-(N-acetylcystein-S-yl)-α-MeDA all stimulated the proliferation of glial fibrillary acidic protein-positive astrocytes at a dose of 10 µM. The findings indicate that glial cells are activated in response to MDMA/MDA and support a role for thioether metabolites of α-MeDA in the neurotoxicity.

  15. Spontaneous glial calcium waves in the retina develop over early adulthood.

    PubMed

    Kurth-Nelson, Zeb L; Mishra, Anusha; Newman, Eric A

    2009-09-09

    Intercellular glial Ca(2+) waves constitute a signaling pathway between glial cells. Artificial stimuli have previously been used to evoke these waves, and their physiological significance has been questioned. We report here that Ca(2+) waves occur spontaneously in rat retinal glial cells, both in the isolated retina and in vivo. These spontaneous waves are propagated by ATP release. In the isolated retina, suramin (P2 receptor antagonist) reduces the frequency of spontaneous wave generation by 53%, and apyrase (ATP-hydrolyzing enzyme) reduces frequency by 95-100%. Luciferin-luciferase chemiluminescence reveals waves of ATP matching the spontaneous Ca(2+) waves, indicating that ATP release occurs as spontaneous Ca(2+) waves are generated. Wave generation also depends on age. Spontaneous wave frequency rises from 0.27 to 1.0 per minute per mm(2), as rats age from 20 to 120 d. The sensitivity of glia to ATP does not increase with age, but the ATP released by evoked waves is 31% greater in 120-d-old than in 20-d-old rats, suggesting that increased ATP release in older animals could account for the higher frequency of wave generation. Simultaneous imaging of glial Ca(2+) and arterioles in the isolated retina demonstrates that spontaneous waves alter vessel diameter, implying that spontaneous waves may have a significant impact on retinal physiology. Spontaneous intercellular glial Ca(2+) waves also occur in the retina in vivo, with frequency, speed, and diameter similar to the isolated retina. Increased spontaneous wave occurrence with age suggests that wave generation may be related to retinal pathology.

  16. Glial Cell Contribution to Basal Vessel Diameter and Pressure-Initiated Vascular Responses in Rat Retina

    PubMed Central

    Li, Hui; Bui, Bang V.; Cull, Grant; Wang, Fang; Wang, Lin

    2017-01-01

    Purpose The purpose of this study was to test the hypothesis that retinal glial cells modify basal vessel diameter and pressure-initiated vascular regulation in rat retina. Methods In rats, L-2-aminoadipic acid (LAA, 10 nM) was intravitreally injected to inhibit glial cell activity. Twenty-four hours following injection, retinal glial intracellular calcium (Ca2+) was labeled with the fluorescent calcium indicator Fluo-4/AM (F4, 1 mM). At 110 minutes after injection, intraocular pressure (IOP) was elevated from 20 to 50 mm Hg. Prior to and during IOP elevation, Ca2+ and retinal vessel diameter were assessed using a spectral-domain optical coherence tomography/confocal scanning laser ophthalmoscope. Dynamic changes in Ca2+ and diameter from IOP elevation were quantified. The response in LAA-treated eyes was compared with vehicle treated control eyes. Results L-2-Aminoadipic acid treatment significantly reduced F4-positive cells in the retina (LAA, 16 ± 20 vs. control, 55 ± 37 cells/mm2; P = 0.02). Twenty-four hours following LAA treatment, basal venous diameter was increased from 38.9 ± 3.9 to 51.8 ± 6.4 μm (P < 0.0001, n = 20), whereas arterial diameter was unchanged (from 30.3 ± 3.5 to 30.7 ± 2.8 μm; P = 0.64). In response to IOP elevation, LAA-treated eyes showed a smaller increase in glial cell Ca2+ around both arteries and veins in comparison with control (P < 0.001 for both). There was also significantly greater IOP-induced vasoconstriction in both vessel types (P = 0.05 and P = 0.02, respectively; n = 6 each). Conclusions The results suggest that glial cells can modulate basal retinal venous diameter and contribute to pressure-initiated vascular responses. PMID:28055098

  17. Comparative properties of optically clear epoxy encapsulants

    NASA Astrophysics Data System (ADS)

    Edwards, Maury; Zhou, Yan

    2001-12-01

    Three epoxy systems were evaluated for physical dn optical properties. The three systems chosen for the study were selected on the basis of their optical clarity, color and chemistry. Three distinctly different chemistries were chosen, aromatic epoxy-amine cured. Aromatic epoxy- anhydride cured and cycloaliphatic epoxy-anhydride cured. All three systems remained optically clear and water-white after full cure. The three selected systems were tested for physical properties, adhesion and light transmission properties. Light transmission was measured after thermal and humidity exposure. Adhesion was measured after humidity exposure only. Both of the epoxy-anhydride systems performed well in optical properties but poorer in adhesion as compared to the epoxy-amine system. The aromatic epoxy- amine system discolored badly during thermal exposure at 100 C. Data generated from this work will be used in selecting clear encapsulating materials for photonics applications. No single system offers optimal performance in all areas. The best compromise material is the aromatic epoxy-anhydride system.

  18. Orthodontic Tooth Movement with Clear Aligners

    PubMed Central

    Drake, Carl T.; McGorray, Susan P.; Dolce, Calogero; Nair, Madhu; Wheeler, Timothy T.

    2012-01-01

    Clear aligners provide a convenient model to measure orthodontic tooth movement (OTM). We examined the role of in vivo aligner material fatigue and subject-specific factors in tooth movement. Fifteen subjects seeking orthodontic treatment at the University of Florida were enrolled. Results were compared with data previously collected from 37 subjects enrolled in a similar protocol. Subjects were followed prospectively for eight weeks. An upper central incisor was programmed to move 0.5 mm. every two weeks using clear aligners. A duplicate aligner was provided for the second week of each cycle. Weekly polyvinyl siloxane (PVS) impressions were taken, and digital models were fabricated to measure OTM. Initial and final cone beam computed tomography (CBCT) images were obtained to characterize OTM. Results were compared to data from a similar protocol, where subjects received a new aligner biweekly. No significant difference was found in the amount of OTM between the two groups, with mean total OTM of 1.11 mm. (standard deviation (SD) 0.30) and 1.07 mm. (SD 0.33) for the weekly aligner and biweekly control groups, respectively (P = 0.72). Over eight weeks, in two-week intervals, material fatigue does not play a significant role in the rate or amount of tooth movement. PMID:22928114

  19. Development of Temperature Patterns during Clear Nights.

    NASA Astrophysics Data System (ADS)

    Gustavsson, Torbjörn; Karlsson, Maria; Bogren, Jörgen; Lindqvist, Sven

    1998-06-01

    This paper examines nocturnal air temperature structure development in complex terrain. Clear nights were studied in order to compare the cooling rate in different topographical areas with a variety of land cover. It was found that large variations in temperature developed over a very short time period after sunset and that in situ cooling was the dominant factor causing this in valleys and other wind-sheltered locations. Shelter can be provided both from valley sides and from nearby trees with the main effect being to reduce the vertical mixing.The nighttime increase in temperature difference between valley bottoms and nearby reference areas was interpreted to be due to cold airflows. This was also shown by the increasing lateral extension of cold air accumulating in valleys. This development was found only in open valley locations. Sheltered areas cooled at a much faster rate than exposed sites during early evening. Further cooling did not increase the lateral extension of cold air or result in larger temperature differences. This is attributed to lack of cold airflow. The rapid cooling was supported due to reduced mixing of warmer air from above. This hypothesis was further confirmed in this study by analysis of clear nights with low regional wind speed when it was found that sheltered locations differed significantly in temperature compared to wind-exposed areas.

  20. Geometric sensitivity of ClearPET™ Neuro

    NASA Astrophysics Data System (ADS)

    Gundlich, Brigitte; Weber, Simone

    2007-02-01

    ClearPET™ Neuro is a small-animal positron emission tomography (PET) scanner dedicated to brain studies on rats and primates. The design of ClearPET™ Neuro leads to a specific geometric sensitivity, characterized by inhomogeneous and, depending on the measurement setup, even incomplete data. With respect to reconstruction techniques, homogeneous and complete data sets are a 'must' for analytical reconstruction methods, whereas iterative methods take the geometrical sensitivity into account during the reconstruction process. Nevertheless, here a homogeneous geometric sensitivity over the field of view is highly desirable. Therefore, this contribution aims at studying the impact of different scanner geometries and measurement setups on the geometric sensitivity. A data set of coincident events is computed for certain settings that contains each possible crystal combination once. The lines of response are rebinned into normalizing sinograms and backprojected into sensitivity images. Both, normalizing sinograms and sensitivity images mirror the geometric sensitivity and therefore, provide information which setting enables most complete and homogeneous data sets. An optimal measurement setup and scanner geometry in terms of homogeneous geometric sensitivity is found by analyzing the sensitivity images.

  1. Malignant Clear Cell Hidradenoma of the Breast

    PubMed Central

    Rahal, Ahmad K.; Reddy, Pavan S; Kallail, K. James

    2017-01-01

    A 58-year-old female had a mass in the right breast palpable beneath the areola. A mammogram revealed a 1.5-centimeter soft tissue density that was confirmed with a subsequent ultrasound. The patient underwent a core needle biopsy which was initially reported as a moderately differentiated invasive ductal carcinoma. Immunohistochemical analysis revealed negative staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2), mammaglobin, and gross cystic disease fluid protein 15 (GCDFP-15). A wide local excision of the mass was performed. The pathology report stated the tumor had an infiltrative growth pattern with a desmoplastic stromal response with enhanced epithelial atypia consistent with malignant transformation of a nodular clear cell hidradenoma. Clear cell hidradenoma is a very rare tumor originating from the sweat gland and has a propensity for the face and extremities. The malignant variant of this tumor is extremely rare and has been reported to originate from the breast in few cases. This case represents the difficulty in diagnosing this tumor along with the radiographic and histologic features that can distinguish this malignancy from other entities.

  2. Mathematical and experimental approaches to identify and predict the effects of chemotherapy on neuroglial precursors

    PubMed Central

    Hyrien, Ollivier; Dietrich, Jörg; Noble, Mark

    2010-01-01

    The adverse effects of chemotherapy on normal cells of the body create substantial clinical problems for many cancer patients. Relatively little is known, however, about the effects, other than promotion of cell death, of such agents on the function of normal precursor cells critical in tissue homeostasis and repair. We have combined mathematical and experimental analyses to identify the effects of sublethal doses of chemotherapy on glial precursor cells of the central nervous system (CNS). We modeled the temporal development of a population of precursor and terminally differentiated cells exposed to sublethal doses of carmustine (BCNU), a classical alkylating chemotherapeutic agent used in treatment of gliomas and non-Hodgkin’s lymphomas, as a multi-type age-dependent branching process. We fitted our model to data from in vitro clonal experiments using the method of pseudo-likelihood. This approach identifies several novel drug effects, including modification of the cell cycle length, the time between division and differentiation, and alteration in the probability of undergoing self-renewal division in precursor cells. These changes of precursor cell function in the chemotherapy-exposed brain may have profound clinical implications. Major Findings We applied our computational approach to analyze the effects of BCNU on clonal cultures of oligodendrocyte progenitor cells – one of the best-characterized neural progenitor cells in the mammalian brain. Our analysis reveals that transient exposures to BCNU increased the cell cycle length of progenitor cells and decreased their time to differentiation, while also decreasing the likelihood that they will undergo self-renewing divisions. By investigating the behavior of our mathematical model we demonstrate that precursor cell populations should recover spontaneously from transient modifications of the timing of division and of differentiation, but such recovery will not happen after alteration of cell fate. These

  3. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    SciTech Connect

    Boku, Shuken; Nakagawa, Shin; Takamura, Naoki; Kato, Akiko; Takebayashi, Minoru; Hisaoka-Nakashima, Kazue; Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  4. Manduca Contactin Regulates Amyloid Precursor Protein-Dependent Neuronal Migration

    PubMed Central

    Ramaker, Jenna M.; Swanson, Tracy L.

    2016-01-01

    Amyloid precursor protein (APP) was originally identified as the source of β-amyloid peptides that accumulate in Alzheimer's disease (AD), but it also has been implicated in the control of multiple aspects of neuronal motility. APP belongs to an evolutionarily conserved family of transmembrane proteins that can interact with a variety of adapter and signaling molecules. Recently, we showed that both APP and its insect ortholog [APPL (APP-Like)] directly bind the heterotrimeric G-protein Goα, supporting the model that APP can function as an unconventional Goα-coupled receptor. We also adapted a well characterized assay of neuronal migration in the hawkmoth, Manduca sexta, to show that APPL–Goα signaling restricts ectopic growth within the developing nervous system, analogous to the role postulated for APP family proteins in controlling migration within the mammalian cortex. Using this assay, we have now identified Manduca Contactin (MsContactin) as an endogenous ligand for APPL, consistent with previous work showing that Contactins interact with APP family proteins in other systems. Using antisense-based knockdown protocols and fusion proteins targeting both proteins, we have shown that MsContactin is selectively expressed by glial cells that ensheath the migratory neurons (expressing APPL), and that MsContactin–APPL interactions normally prevent inappropriate migration and outgrowth. These results provide new evidence that Contactins can function as authentic ligands for APP family proteins that regulate APP-dependent responses in the developing nervous system. They also support the model that misregulated Contactin–APP interactions might provoke aberrant activation of Goα and its effectors, thereby contributing to the neurodegenerative sequelae that typify AD. SIGNIFICANCE STATEMENT Members of the amyloid precursor protein (APP) family participate in many aspects of neuronal development, but the ligands that normally activate APP signaling have remained

  5. 75 FR 27338 - NASDAQ OMX Commodities Clearing-Contract Merchant LLC; NASDAQ OMX Commodities Clearing-Delivery...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... Commodities Clearing--Delivery LLC; NASDAQ OMX Commodities Clearing--Finance LLC; Notice of Filing May 6, 2010... Commodities Clearing--Delivery LLC, and NASDAQ OMX Commodities Clearing--Finance LLC filed a supplement to...

  6. The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function.

    PubMed

    Macdonald, J M; Doherty, J; Hackett, R; Freeman, M R

    2013-09-01

    After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1 →MKK4 →dJNK →dAP-1 signaling cascade appears to be activation of draper expression after axon injury.

  7. Radio HF precursors of Earthquakes

    NASA Astrophysics Data System (ADS)

    Ruzhin, Yu.; Nomicos, C.; Vallianatos, F.; Shpakovsky, V.

    The high frequency (HF) earthquake electromagnetic precursors (40-55MHz band) were recorded by the four electromagnetic stations a few days (hours) prior the event associated with earthquakes with magnitude more than 5.0 at Crete Island. These experiments were performed continuously during 1998-2002 and specific peculiarities are found. This is underhorizon epicenter position for main part of events under question. Another unusual result is that such HF preseismic radio noise-like signals are responsible for seaquakes too. We made conclusion about developing of some thunderstorm-like charged clouds activity in atmosphere before the seismic event. As result of our analysis and interpretation of the available data of continuous observations on a network of Crete island we should state here, that in an atmosphere above the sea on the eve of earthquake at heights of 0.1-10 km the spatially distributed spots of sporadic charged clouds are occurred and the conditions for the electrical discharges in an atmosphere are created which can serve a source of HF radio-emission registered by Crete network. The atmosphere theory relations are used to model a corresponding to an anomalous event emissions generation observed on the Crete. The supposed mechanism of preseismic electricity generation is the model of convection carrier started in an atmosphere. It is governed by the horizontal gradient of air temperature. The occurrence of electrical charges in a surface of the sea and transportation them further on heights up to 10 km in our model occurs due to sporadic energy injections that allocated within bottom of the sea as gases and heat. The dimensions of width and height govern the size of atmosphere convection cells in the earthquake preparation area. These dimensions of the sporadic spots are close to 3 km each as it is derived from shadow geometry and spectral fluctuations of HF signal. Based on experience of Crete HF precursors observation the method for satellite mapping

  8. Leading time domain seismic precursors

    NASA Astrophysics Data System (ADS)

    Boucouvalas, A. C.; Gkasios, M.; Keskebes, A.; Tselikas, N. T.

    2014-08-01

    The problem of predicting the occurrence of earthquakes is threefold. On one hand it is necessary to predict the date and magnitude of an earthquake, and on the other hand the location of the epicenter. In this work after a brief review of the state of earthquake prediction research, we report on a new leading time precursor for determining time onset of earthquake occurrence. We report the linking between earthquakes of the past with those which happen in the future via Fibonacci, Dual and Lucas numbers (FDL) numbers. We demonstrate it here with two example seed earthquakes at least 100 years old. Using this leading indicator method we can predict significant earthquake events >6.5R, with good accuracy approximately +- 1 day somewhere in the world. From a single seed we produce at least 100 trials simultaneously of which 50% are correct to +- 1day. The indicator is based on Fibonacci, Dual and Lucas numbers (FDL). This result hints that the log periodic FDL numbers are at the root of the understanding of the earthquake mechanism. The theory is based on the assumption that each occurred earthquake discontinuity can be thought of as a generating source of FDL time series. (The mechanism could well be linked to planetary orbits). When future dates are derived from clustering and convergence from previous strong earthquake dates at an FDL time distance, then we have a high probability for an earthquake to occur on that date. We set up a real time system which generates FDL time series from each previous significant earthquake (>7R) and we produce a year to year calendar of high probability earthquake dates. We have tested this over a number of years with considerable success. We have applied this technique for strong (>7R) earthquakes across the globe as well as on a restricted region such as the Greek geographic region where the magnitude is small (>4R-6.5R). In both cases the success of the method is impressive. It is our belief that supplementing this method with

  9. Amyloid precursor protein modulates macrophage phenotype and diet-dependent weight gain

    PubMed Central

    Puig, Kendra L.; Brose, Stephen A.; Zhou, Xudong; Sens, Mary A.; Combs, Gerald F.; Jensen, Michael D.; Golovko, Mikhail Y.; Combs, Colin K.

    2017-01-01

    It is well known that mutations in the gene coding for amyloid precursor protein are responsible for autosomal dominant forms of Alzheimer’s disease. Proteolytic processing of the protein leads to a number of metabolites including the amyloid beta peptide. Although brain amyloid precursor protein expression and amyloid beta production are associated with the pathophysiology of Alzheimer’s disease, it is clear that amyloid precursor protein is expressed in numerous cell types and tissues. Here we demonstrate that amyloid precursor protein is involved in regulating the phenotype of both adipocytes and peripheral macrophages and is required for high fat diet-dependent weight gain in mice. These data suggest that functions of this protein include modulation of the peripheral immune system and lipid metabolism. This biology may have relevance not only to the pathophysiology of Alzheimer’s disease but also diet-associated obesity. PMID:28262782

  10. Application of Plasma Spraying as a Precursor in the Synthesis of Oxidation-Resistant Coatings

    NASA Astrophysics Data System (ADS)

    Ritt, P.; Lu-Steffes, O.; Sakidja, R.; Perepezko, J. H.; Lenling, W.; Crawmer, D.; Beske, J.

    2013-08-01

    Thermal spray methods offer a versatile and flexible approach to the manufacture of coatings as a final product. A novel application of thermal spray coating is demonstrated by incorporating a plasma-sprayed Mo layer coating as a precursor step within an integrated costing design. The effectiveness of the two-step design is illustrated for aluminoborosilica coatings on SiC/C composites and W substrates based on the plasma-sprayed Mo precursor and subsequent codeposition of Si and B by a pack cementation method. Even with incomplete precursor coverage, an aluminoborosilica coating is developed because of the high initial fluidity of the as-pack coating. An effective oxidation resistance is observed following exposure at elevated temperatures (1373-1673 K) in ambient air and during torch testing at 1773 K, providing clear evidence that the plasma spraying of Mo is a viable precursor step in the formation of the oxidation-resistant Mo-Si-B-based coating.

  11. ClearSee: a rapid optical clearing reagent for whole-plant fluorescence imaging

    PubMed Central

    Kurihara, Daisuke; Mizuta, Yoko; Sato, Yoshikatsu; Higashiyama, Tetsuya

    2015-01-01

    Imaging techniques for visualizing and analyzing precise morphology and gene expression patterns are essential for understanding biological processes during development in all organisms. With the aid of chemical screening, we developed a clearing method using chemical solutions, termed ClearSee, for deep imaging of morphology and gene expression in plant tissues. ClearSee rapidly diminishes chlorophyll autofluorescence while maintaining fluorescent protein stability. By adjusting the refractive index mismatch, whole-organ and whole-plant imaging can be performed by both confocal and two-photon excitation microscopy in ClearSee-treated samples. Moreover, ClearSee is applicable to multicolor imaging of fluorescent proteins to allow structural analysis of multiple gene expression. Given that ClearSee is compatible with staining by chemical dyes, the technique is useful for deep imaging in conjunction with genetic markers and for plant species not amenable to transgenic approaches. This method is useful for whole imaging for intact morphology and will help to accelerate the discovery of new phenomena in plant biological research. PMID:26493404

  12. The protease Ste24 clears clogged translocons

    PubMed Central

    Ast, Tslil; Michaelis, Susan; Schuldiner, Maya

    2015-01-01

    Summary Translocation into the endoplasmic reticulum (ER) is the first step in the biogenesis of thousands of eukaryotic endomembrane proteins. While functional ER translocation has been avidly studied, little is known about the quality control mechanisms that resolve faulty translocational states. One such faulty state is translocon clogging, in which the substrate fails to properly translocate and obstructs the translocon pore. To shed light on the machinery required to resolve clogging, we carried out a systematic screen in Saccharomyces cerevisiae that highlighted a role for the ER metalloprotease Ste24. We could demonstrate that Ste24 approaches the translocon upon clogging, interacts with and generates cleavage fragments of the clogged protein. Importantly, these functions are conserved in the human homologue, ZMPSTE24, while disease-associated mutant forms of ZMPSTE24 fail to clear the translocon. These results shed light on a new and critical task of Ste24, which safe-guards the essential process of translocation. PMID:26771486

  13. 17 CFR 22.2 - Futures Commission Merchants: Treatment of Cleared Swaps and Associated Cleared Swaps Customer...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...: Treatment of Cleared Swaps and Associated Cleared Swaps Customer Collateral. 22.2 Section 22.2 Commodity and... Commission Merchants: Treatment of Cleared Swaps and Associated Cleared Swaps Customer Collateral. (a... Customers and associated Cleared Swaps Customer Collateral as belonging to Cleared Swaps Customers....

  14. Silver stainings distinguish Lewy bodies and glial cytoplasmic inclusions: comparison between Gallyas-Braak and Campbell-Switzer methods.

    PubMed

    Uchihara, Toshiki; Nakamura, Ayako; Mochizuki, Yoko; Hayashi, Masaharu; Orimo, Satoshi; Isozaki, Eiji; Mizutani, Toshio

    2005-09-01

    Lewy bodies (LBs) of idiopathic Parkinson's disease and glial cytoplasmic inclusions (GCIs) of multiple system atrophy are pathological deposits both composed of phosphorylated alpha-synuclein woven into different filaments. Although both LBs and GCIs are considered to be hallmarks for each independent synucleinopathy, until now they could not be clearly distinguished on the basis of their biochemical or immunohistochemical features. We have examined possible differences in their argyrophilic features and their relation to synuclein-like or ubiquitin-like immunoreactivity (IR). Pairs of mirror sections from different brain areas were triple-fluorolabeled with an anti-alpha-synuclein antibody, an anti-ubiquitin antibody and thiazin red (TR), a fluorochrome that labels fibrillary structures such as Lewy bodies or neurofibrillary tangles. One of the paired sections was subsequently stained using the Campbell-Switzer method (CS), and the other by the Gallyas-Braak method (GB). By comparing of the same microscopic field on the paired fluorolabeled sections, subsequently silver-stained with either CS or GB, five different profiles of each structure could be determined: alpha-synuclein-like IR, ubiquitin-like IR, affinity to TR, argyrophilia with CS or GB. GCIs exhibited argyrophilia with both CS and GB but lacked affinity to TR. In contrast, LBs exhibited argyrophilia with CS but not with GB and some affinity to TR. These disease-specific profiles of argyrophilia were consistent, and were not influenced by areas or cases examined. Although immunohistochemical features of LBs and GCIs were similar in exhibiting IR for alpha-synuclein and ubiquitin, the contrast in their argyrophilic profiles may indicate possible differences in the molecular composition or conformation of alpha-synuclein. Even though these empirical differences still remain to be explained, awareness of this clear distinction is potentially of diagnostic and pathological relevance.

  15. Expression of vimentin and glial fibrillary acidic protein in the developing rat spinal cord: an immunocytochemical study of the spinal cord glial system.

    PubMed Central

    Oudega, M; Marani, E

    1991-01-01

    The glial system in the developing rat spinal cord was studied using immunocytochemistry. Antibodies to vimentin and glial fibrillary acidic protein (GFAP) were used. At E11, vimentin was first found in the membrana limitans externa. In the matrix layer, short vimentin protrusions were found near the membrana limitans externa at E12. In addition, vimentin was scattered throughout the matrix layer, where it was also present as vimentin-positive tangles. Later in development, vimentin immunoreactivity was distributed in a distinct radial pattern in the matrix layer. During the first postnatal weeks, vimentin was replaced by GFAP which is therefore expressed in a similar radial pattern. This orderly structural organisation of vimentin and GFAP in the matrix layer could indicate the involvement of both proteins in morphogenetic processes such as neuron migration and cell organisation. In the mantle layer, a distinct radial vimentin immunoreactivity was replaced by GFAP immunoreactivity during the first 2 postnatal weeks. In addition, GFAP fibres appeared first, at E18, in the ventral mantle layer associated with the motor neuron columns. These glial fibres originated from a local source. In the dorsal mantle layer, GFAP-positive fibres were oriented tangentially, which is different from the overall radial arrangement. This expression pattern may be related to the ingrowth of primary afferents. In the ventral and dorsal raphe, a major vimentin expression was replaced by a minor presence of GFAP. Within the white matter, a vimentin-positive radial pattern was demonstrated which, after birth, was replaced by GFAP. This palisading pattern suggested an involvement of both proteins in the development and guidance of the ascending and descending spinal cord fibre systems. The general transition from the expression of vimentin to the expression of GFAP in the rat spinal cord takes place during the first 3 postnatal weeks. Images Fig. 2 (cont.) Fig. 2 Fig. 3 Fig. 4 (cont.) Fig

  16. Chemokines influence the migration and fate of neural precursor cells from the young adult and middle-aged rat subventricular zone.

    PubMed

    Gordon, R J; Mehrabi, N F; Maucksch, C; Connor, B

    2012-01-01

    We have previously demonstrated a role for the chemokines MCP-1, MIP-1α and GRO-α in directing subventricular zone (SVZ)-derived neural precursor cell migration towards the site of cell death in the adult rodent brain. However the influence of chemokines such as MCP-1, MIP-1α and GRO-α on the differentiation of adult neural precursor cells has not previously been investigated. Further, as the majority of neurological disorders and injuries occur during ageing, it is important to investigate the effect of chemokines on adult neural precursor cell cultures obtained from the ageing brain. This study therefore examined the effect of MCP-1, MIP-1α and GRO-α on SVZ-derived neural precursor cell differentiation in vitro, and assessed whether precursor cells from the middle-aged rat brain (13 months old) follow the same migratory and differential profile as neural precursor cells obtained from the young adult rat brain (2 months old). We observed that each of the chemokines examined generated differing effects in regards to neuronal or glial differentiation. Further, both MIP-1α and GRO-α increased total cell number, suggesting an effect on precursor cell proliferation and/or survival. In agreement with cultures obtained from young adult brains, SVZ-derived neural precursor cells cultured from the middle-aged brain exhibited chemotactic migration in response to a concentration gradient. These results indicate that the chemokines MCP-1, MIP-1α and GRO-α can influence both the migration and fate choice of SVZ-derived neural precursor cells, as well as promoting cell viability. While a response to each of these chemokines is maintained in the middle-aged brain, a distinct age-related alteration in differential fate can be identified.

  17. The Interrelationships of Mathematical Precursors in Kindergarten

    ERIC Educational Resources Information Center

    Cirino, Paul T.

    2011-01-01

    This study evaluated the interrelations among cognitive precursors across quantitative, linguistic, and spatial attention domains that have been implicated for math achievement in young children. The dimensionality of the quantity precursors was evaluated in 286 kindergarteners via latent variable techniques, and the contribution of precursors…

  18. All brains are made of this: a fundamental building block of brain matter with matching neuronal and glial masses

    PubMed Central

    Mota, Bruno; Herculano-Houzel, Suzana

    2014-01-01

    How does the size of the glial and neuronal cells that compose brain tissue vary across brain structures and species? Our previous studies indicate that average neuronal size is highly variable, while average glial cell size is more constant. Measuring whole cell sizes in vivo, however, is a daunting task. Here we use chi-square minimization of the relationship between measured neuronal and glial cell densities in the cerebral cortex, cerebellum, and rest of brain in 27 mammalian species to model neuronal and glial cell mass, as well as the neuronal mass fraction of the tissue (the fraction of tissue mass composed by neurons). Our model shows that while average neuronal cell mass varies by over 500-fold across brain structures and species, average glial cell mass varies only 1.4-fold. Neuronal mass fraction varies typically between 0.6 and 0.8 in all structures. Remarkably, we show that two fundamental, universal relationships apply across all brain structures and species: (1) the glia/neuron ratio varies with the total neuronal mass in the tissue (which in turn depends on variations in average neuronal cell mass), and (2) the neuronal mass per glial cell, and with it the neuronal mass fraction and neuron/glia mass ratio, varies with average glial cell mass in the tissue. We propose that there is a fundamental building block of brain tissue: the glial mass that accompanies a unit of neuronal mass. We argue that the scaling of this glial mass is a consequence of a universal mechanism whereby numbers of glial cells are added to the neuronal parenchyma during development, irrespective of whether the neurons composing it are large or small, but depending on the average mass of the glial cells being added. We also show how evolutionary variations in neuronal cell mass, glial cell mass and number of neurons suffice to determine the most basic characteristics of brain structures, such as mass, glia/neuron ratio, neuron/glia mass ratio, and cell densities. PMID:25429260

  19. Method of texturing a superconductive oxide precursor

    DOEpatents

    DeMoranville, Kenneth L.; Li, Qi; Antaya, Peter D.; Christopherson, Craig J.; Riley, Jr., Gilbert N.; Seuntjens, Jeffrey M.

    1999-01-01

    A method of forming a textured superconductor wire includes constraining an elongated superconductor precursor between two constraining elongated members placed in contact therewith on opposite sides of the superconductor precursor, and passing the superconductor precursor with the two constraining members through flat rolls to form the textured superconductor wire. The method includes selecting desired cross-sectional shape and size constraining members to control the width of the formed superconductor wire. A textured superconductor wire formed by the method of the invention has regular-shaped, curved sides and is free of flashing. A rolling assembly for single-pass rolling of the elongated precursor superconductor includes two rolls, two constraining members, and a fixture for feeding the precursor superconductor and the constraining members between the rolls. In alternate embodiments of the invention, the rolls can have machined regions which will contact only the elongated constraining members and affect the lateral deformation and movement of those members during the rolling process.

  20. The interrelationships of mathematical precursors in kindergarten.

    PubMed

    Cirino, Paul T

    2011-04-01

    This study evaluated the interrelations among cognitive precursors across quantitative, linguistic, and spatial attention domains that have been implicated for math achievement in young children. The dimensionality of the quantity precursors was evaluated in 286 kindergarteners via latent variable techniques, and the contribution of precursors from each domain was established for small sums addition. Results showed a five-factor structure for the quantity precursors, with the major distinction being between nonsymbolic and symbolic tasks. The overall model demonstrated good fit and strong predictive power (R(2)=55%) for addition number combinations. Linguistic and spatial attention domains showed indirect relationships with outcomes, with their effects mediated by symbolic quantity measures. These results have implications for the measurement of mathematical precursors and yield promise for predicting future math performance.

  1. Molecular Profiling of Clear Cell Ovarian Cancers

    PubMed Central

    Friedlander, Michael L.; Russell, Kenneth; Millis, Sherri; Gatalica, Zoran; Bender, Ryan; Voss, Andreas

    2016-01-01

    Background Advanced stage/recurrent clear cell ovarian cancers (CCOCs) are characterized by a low response to chemotherapy and a poor prognosis. There is growing interest in investigating novel/molecular targeted therapies in patients with CCOC in histotype-specific trials. However, CCOCs are not a uniform entity and comprise a number of molecular subtypes and it is unlikely that a single approach to treatment will be appropriate for all patients. The aim of this study was to analyze the results of a multiplatform profiling panel in CCOCs to identify potential therapeutic targets. Patients and Methods Tumor profiling was performed on 521 CCOCs. They were grouped into pure (n = 422) and mixed (n = 99) CCOC for analysis. Testing included a combination of DNA sequencing (including next-generation sequencing) using a 46-gene panel, immunohistochemistry, fluorescent or chromogenic in situ hybridization, and RNA fragment analysis. Results The most common findings were in the PIK3CA/Akt/mTOR pathway, with 61% of all CCOCs showing a molecular alteration in one of these pathway components. Next-generation sequencing revealed PIK3CA mutations in 50% of pure CCOCs. Significant differences were observed between pure and mixed CCOCs with respect to hormone receptor expression (9% vs 34.7% for ER, 13.45 vs 26.4% for PR), cMET (24.1% vs 11.6%), PD-1 tumor infiltrating lymphocytes (48.1% vs 100%), expression of PD-L1 (7.4% vs 25%), and TOPO1 (41% vs 27.1%) on immunohistochemistry, whereas next-generation sequencing revealed significant differences in mutation frequency in PIK3CA (50% vs 18.5%), TP53 (18.1% vs 57.7%), KRAS (12.4% vs 3.7%), and cMET (1.9% vs 11.1%). Conclusions This large study confirms that the PIK3CA/Akt/mTOR pathway is commonly altered in CCOCs, and highlights the significant differences between pure and mixed CCOCs. Clear cell ovarian cancers are molecularly heterogeneous and there are a number of potential therapeutic targets which could be tested in clinical

  2. Molecular effective coverage surface area of optical clearing agents for predicting optical clearing potential

    NASA Astrophysics Data System (ADS)

    Feng, Wei; Ma, Ning; Zhu, Dan

    2015-03-01

    The improvement of methods for optical clearing agent prediction exerts an important impact on tissue optical clearing technique. The molecular dynamic simulation is one of the most convincing and simplest approaches to predict the optical clearing potential of agents by analyzing the hydrogen bonds, hydrogen bridges and hydrogen bridges type forming between agents and collagen. However, the above analysis methods still suffer from some problem such as analysis of cyclic molecule by reason of molecular conformation. In this study, a molecular effective coverage surface area based on the molecular dynamic simulation was proposed to predict the potential of optical clearing agents. Several typical cyclic molecules, fructose, glucose and chain molecules, sorbitol, xylitol were analyzed by calculating their molecular effective coverage surface area, hydrogen bonds, hydrogen bridges and hydrogen bridges type, respectively. In order to verify this analysis methods, in vitro skin samples optical clearing efficacy were measured after 25 min immersing in the solutions, fructose, glucose, sorbitol and xylitol at concentration of 3.5 M using 1951 USAF resolution test target. The experimental results show accordance with prediction of molecular effective coverage surface area. Further to compare molecular effective coverage surface area with other parameters, it can show that molecular effective coverage surface area has a better performance in predicting OCP of agents.

  3. Clear, Aqueous Topical Drop of Triamcinolone Acetonide.

    PubMed

    Trinh, Hoang M; Cholkar, Kishore; Joseph, Mary; Yang, Xiaoyan; Mitra, Ashim K

    2017-02-09

    The objective of this study was to develop a clear aqueous mixed nanomicellar formulation (NMF) of triamcinolone acetonide (TA) with a combination of nonionic surfactant hydrogenated castor oil 60 (HCO-60) and octoxynol-40 (Oc-40). In order to delineate the effects of drug-polymer interactions on entrapment efficiency (EE), loading efficiency (LE), and critical micellar concentration (CMC), a design of experiment (DOE) was performed to optimize the formulation. In this study, full-factorial design has been used with HCO-60 and OC-40 as independent variables. All formulations were prepared following solvent evaporation and film rehydration method, characterized with size, polydispersity, shape, morphology, EE, LE, and CMC. A specific blend of HCO-60 and Oc-40 at a particular wt% ratio (5:1.5) produced highest drug EE, LE, and smallest CMC (0.0216 wt%). Solubility of TA in NMF improved 20 times relative to normal aqueous solubility. Qualitative (1)H NMR studies confirmed the absence of free drug in the outer aqueous NMF medium. Moreover, TA-loaded NMF appeared to be highly stable and well tolerated on human corneal epithelial cells (HCEC) and human retinal pigment epithelial cells (D407 cells). Overall, these studies suggest that TA in NMF is safe and suitable for human topical ocular drop application.

  4. Radial Glia Inhibit Peripheral Glial Infiltration into the Spinal Cord at Motor Exit Point Transition Zones

    PubMed Central

    Smith, Cody J.; Johnson, Kimberly; Welsh, Taylor G.; Barresi, Michael J. F.; Kucenas, Sarah

    2016-01-01

    In the mature vertebrate nervous system, central and peripheral nervous system (CNS and PNS, respectively) GLIA myelinate distinct motor axon domains at the motor exit point transition zone (MEP TZ). How these cells preferentially associate with and myelinate discrete, non-overlapping CNS versus PNS axonal segments, is unknown. Using in vivo imaging and genetic cell ablation in zebrafish, we demonstrate that radial glia restrict migration of PNS glia into the spinal cord during development. Prior to development of radial glial endfeet, peripheral cells freely migrate back and forth across the MEP TZ. However, upon maturation, peripherally located cells never enter the CNS. When we ablate radial glia, peripheral glia ectopically migrate into the spinal cord during developmental stages when they would normally be restricted. These findings demonstrate that radial glia contribute to both CNS and PNS development and control the unidirectional movement of glial cell types across the MEP TZ early in development. PMID:27029762

  5. An autopsy case of sudden unexpected death due to a glial cyst of the pineal gland.

    PubMed

    Na, Joo-Young; Lee, Kyung-Hwa; Kim, Hyung-Seok; Park, Jong-Tae

    2014-09-01

    Pineal cysts are usually asymptomatic; however, they may rarely cause symptoms such as chronic headache, paroxysmal headache with gaze paresis, postural syncope, loss of consciousness, and sudden death. A 30-year-old woman with no specific medical history except chronic headache was found collapsed in a public toilet per se. Postmortem examination revealed no external injuries or internal diseases except a cystic lesion of the pineal gland. Histologic examination showed an internal cyst surrounded by glial tissues and pineal parenchyma that was diagnosed as a glial cyst of the pineal gland. Although the pineal cyst cannot be confirmed as the cause of death, it was considered, as no other cause was evident. Herein, we report a pineal cyst considered as an assumed cause of death.

  6. Satellite glial cells in dorsal root ganglia are activated in experimental autoimmune encephalomyelitis.

    PubMed

    Warwick, Rebekah A; Ledgerwood, Craig J; Brenner, Talma; Hanani, Menachem

    2014-05-21

    Pain is a serious and common problem with patients suffering from multiple sclerosis (MS). Very little has been done to investigate the peripheral mechanisms of pain in MS. Here we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to investigate the possible contribution of satellite glial cells (SGCs) to pain in MS. EAE mice had reduced pain thresholds 10 days after disease induction. We examined dorsal root ganglia and found increased expression of glial fibrillary acidic protein in SGCs, a marker of SGC activation, and increased coupling among SGCs, a known component of activated SGCs. Activated SGCs have previously been shown to contribute to pain in other classical neuropathic pain models, suggesting that pain in multiple sclerosis has a peripheral component.

  7. Glutamate release from satellite glial cells of the murine trigeminal ganglion.

    PubMed

    Wagner, Lysann; Warwick, Rebekah A; Pannicke, Thomas; Reichenbach, Andreas; Grosche, Antje; Hanani, Menachem

    2014-08-22

    It has been proposed that glutamate serves as a mediator between neurons and satellite glial cells (SGCs) in sensory ganglia and that SGCs release glutamate. Using a novel method, we studied glutamate release from SGCs from murine trigeminal ganglia. Sensory neurons with adhering SGCs were enzymatically isolated from wild type and transgenic mice in which vesicular exocytosis was suppressed in glial cells. Extracellular glutamate was detected by microfluorimetry. After loading the cells with a photolabile Ca(2+) chelator, the intracellular Ca(2+) concentration was raised in SGCs by a UV pulse, which resulted in glutamate release. The amount of released glutamate was decreased in cells with suppressed exocytosis and after pharmacological block of hemichannels. The data demonstrate that SGCs of the trigeminal ganglion release glutamate in a Ca(2+)-dependent manner.

  8. Properties of angiotensin II receptors in glial cells from the adult corpus callosum.

    PubMed Central

    Matute, C; Pulakat, L; Río, C; Valcárcel, C; Miledi, R

    1994-01-01

    The existence and the properties of angiotensin II receptors in the adult bovine and human corpus callosum (CC) were investigated by using Xenopus oocytes and primary glial cell cultures. In oocytes injected with CC mRNA, angiotensin II elicited oscillatory Cl- currents due to activation of the inositol phosphate/Ca(2+)-receptor-channel coupling system. The receptors expressed in oocytes and in CC cultures were pharmacologically similar to the AT1 receptor type as assayed by binding. Northern blot analysis and in situ hybridization studies in sections from CC and in glial cultures revealed that the receptors were molecularly related to the AT1 receptor and that they were present in astrocytes. In these cells, activation of the receptors with angiotensin II increased de novo DNA synthesis, promoted the release of aldosterone, and induced c-Fos expression. These findings indicate that CC astrocytes possess functional AT1 receptors that participate in various physiological processes. Images PMID:8170986

  9. A glial amino-acid transporter controls synapse strength and courtship in Drosophila.

    PubMed

    Grosjean, Yael; Grillet, Micheline; Augustin, Hrvoje; Ferveur, Jean-François; Featherstone, David E

    2008-01-01

    Mate choice is an evolutionarily critical decision that requires the detection of multiple sex-specific signals followed by central integration of these signals to direct appropriate behavior. The mechanisms controlling mate choice remain poorly understood. Here, we show that the glial amino-acid transporter genderblind controls whether Drosophila melanogaster males will attempt to mate with other males. Genderblind (gb) mutant males showed no alteration in heterosexual courtship or copulation, but were attracted to normally unappealing male species-specific chemosensory cues. As a result, genderblind mutant males courted and attempted to copulate with other Drosophila males. This homosexual behavior could be induced within hours using inducible RNAi, suggesting that genderblind controls nervous system function rather than its development. Consistent with this, and indicating that glial genderblind regulates ambient extracellular glutamate to suppress glutamatergic synapse strength in vivo, homosexual behavior could be turned on and off by altering glutamatergic transmission pharmacologically and/or genetically.

  10. Emerging role of glial cells in the control of body weight

    PubMed Central

    García-Cáceres, Cristina; Fuente-Martín, Esther; Argente, Jesús; Chowen, Julie A.

    2012-01-01

    Glia are the most abundant cell type in the brain and are indispensible for the normal execution of neuronal actions. They protect neurons from noxious insults and modulate synaptic transmission through affectation of synaptic inputs, release of glial transmitters and uptake of neurotransmitters from the synaptic cleft. They also transport nutrients and other circulating factors into the brain thus controlling the energy sources and signals reaching neurons. Moreover, glia express receptors for metabolic hormones, such as leptin and insulin, and can be activated in response to increased weight gain and dietary challenges. However, chronic glial activation can be detrimental to neurons, with hypothalamic astrocyte activation or gliosis suggested to be involved in the perpetuation of obesity and the onset of secondary complications. It is now accepted that glia may be a very important participant in metabolic control and a possible therapeutical target. Here we briefly review this rapidly advancing field. PMID:24024117

  11. Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

    PubMed Central

    Luan, Lan; Wei, Xiaoling; Zhao, Zhengtuo; Siegel, Jennifer J.; Potnis, Ojas; Tuppen, Catherine A; Lin, Shengqing; Kazmi, Shams; Fowler, Robert A.; Holloway, Stewart; Dunn, Andrew K.; Chitwood, Raymond A.; Xie, Chong

    2017-01-01

    Implanted brain electrodes construct the only means to electrically interface with individual neurons in vivo, but their recording efficacy and biocompatibility pose limitations on scientific and clinical applications. We showed that nanoelectronic thread (NET) electrodes with subcellular dimensions, ultraflexibility, and cellular surgical footprints form reliable, glial scar–free neural integration. We demonstrated that NET electrodes reliably detected and tracked individual units for months; their impedance, noise level, single-unit recording yield, and the signal amplitude remained stable during long-term implantation. In vivo two-photon imaging and postmortem histological analysis revealed seamless, subcellular integration of NET probes with the local cellular and vasculature networks, featuring fully recovered capillaries with an intact blood-brain barrier and complete absence of chronic neuronal degradation and glial scar. PMID:28246640

  12. MI Gap Clearing Kicker Magnet Design Review

    SciTech Connect

    Jensen, Chris; /Fermilab

    2008-10-01

    The kicker system requirements were originally conceived for the NOvA project. NOvA is a neutrino experiment located in Minnesota. To achieve the desired neutrino flux several upgrades are required to the accelerator complex. The Recycler will be used as a proton pre-injector for the Main Injector (MI). As the Recycler is the same size as the MI, it is possible to do a single turn fill ({approx}11 {micro}sec), minimizing the proton injection time in the MI cycle and maximizing the protons on target. The Recycler can then be filled with beam while the MI is ramping to extract beam to the target. To do this requires two new transfer lines. The existing Recycler injection line was designed for 10{pi} pbar beams, not the 20{pi} proton beams we anticipate from the Booster. The existing Recycler extraction line allows for proton injection through the MI, while we want direct injection from the Booster. These two lines will be decommissioned. The new injection line from the MI8 line into the Recycler will start at 848 and end with injection kickers at RR104. The new extraction line in the RR30 straight section will start with a new extraction kicker at RR232 and end with new MI injection kickers at MI308. Finally, to reduce beam loss activation in the enclosure, a new gap clearing kicker will be used to extract uncaptured beam created during the slip stack injection process down the existing dump line. It was suggested that the MI could benefit from this type of system immediately. This led to the early installation of the gap clearing system in the MI, followed by moving the system to Recycler during NOvA. The specifications also changed during this process. Initially the rise and fall time requirements were 38 ns and the field stability was {+-}1%. The 38 ns is based on having a gap of 2 RF buckets between injections. (There are 84 RF buckets that can be filled from the Booster for each injection, but 82 would be filled with beam. MI and Recycler contain 588 RF buckets

  13. Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex.

    PubMed

    Voutsinos-Porche, Brigitte; Bonvento, Gilles; Tanaka, Kohichi; Steiner, Pascal; Welker, Egbert; Chatton, Jean-Yves; Magistretti, Pierre J; Pellerin, Luc

    2003-01-23

    Neuron-glia interactions are essential for synaptic function, and glial glutamate (re)uptake plays a key role at glutamatergic synapses. In knockout mice, for either glial glutamate transporters, GLAST or GLT-1, a classical metabolic response to synaptic activation (i.e., enhancement of glucose utilization) is decreased at an early functional stage in the somatosensory barrel cortex following activation of whiskers. Investigation in vitro demonstrates that glial glutamate transport represents a critical step for triggering enhanced glucose utilization, but also lactate release from astrocytes through a mechanism involving changes in intracellular Na(+) concentration. These data suggest that a metabolic crosstalk takes place between neurons and astrocytes in the developing cortex, which would be regulated by synaptic activity and mediated by glial glutamate transporters.

  14. Refractive index matching and clear emulsions.

    PubMed

    Sun, James Ziming; Erickson, Michael C E; Parr, James W

    2005-01-01

    Refractive index (RI) matching is a unique way of making clear emulsions to meet market trends. However, RI matching has not been sufficiently investigated in terms of physical principles and methodologies. Snell's law (n2 sin r2= n1 sin r1) is applicable to cosmetic emulsions. When oil phase and water phase have equal RI (n2 = n1) values, light will not bend as it strikes obliquely at the emulsion interface. Instead, light is transmitted through the emulsion without refraction, which produces clarity. Theoretical RI values in solution can be calculated with summation of the product of the weight percentage and refractive index of each ingredient (RI(mix) = [W1 x n1 + W2 x n2 + W3 x n3 + + Wn x nn]Wtau). Oil-phase RI values are normally at 1.4 or higher. Glycols are used to adjust the water phase RI, since they typically have larger RI values than water. Noticeable deviations from calculated RI values are seen in experimentally prepared solutions. Three basic deviation types are observed: negative, positive, and slightly negative or positive, which can occur in glycol aqueous solutions at different concentrations. The deviations are attributed to changes in molecular interaction between molecules in solution, which can lead to changes in specific gravity. Negative RI deviation corresponds to a decrease in specific gravity, and positive RI deviation corresponds to an increase in specific gravity. RI values will deviate from calculated values since an increase or decrease in specific gravity leads to a change in optical density.

  15. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue.

    PubMed

    Hanrieder, Jörg; Wicher, Grzegorz; Bergquist, Jonas; Andersson, Malin; Fex-Svenningsen, Asa

    2011-07-01

    The development of powerful analytical techniques for specific molecular characterization of neural cell types is of central relevance in neuroscience research for elucidating cellular functions in the central nervous system (CNS). This study examines the use of differential protein expression profiling of mammalian neural cells using direct analysis by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). MALDI-MS analysis is rapid, sensitive, robust, and specific for large biomolecules in complex matrices. Here, we describe a newly developed and straightforward methodology for direct characterization of rodent CNS glial cells using MALDI-MS-based intact cell mass spectrometry (ICMS). This molecular phenotyping approach enables monitoring of cell growth stages, (stem) cell differentiation, as well as probing cellular responses towards different stimulations. Glial cells were separated into pure astroglial, microglial, and oligodendroglial cell cultures. The intact cell suspensions were then analyzed directly by MALDI-TOF-MS, resulting in characteristic mass spectra profiles that discriminated glial cell types using principal component analysis. Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination of different cell types with molecular specificity.

  16. Several synthetic progestins disrupt the glial cell specific-brain aromatase expression in developing zebra fish.

    PubMed

    Cano-Nicolau, Joel; Garoche, Clémentine; Hinfray, Nathalie; Pellegrini, Elisabeth; Boujrad, Noureddine; Pakdel, Farzad; Kah, Olivier; Brion, François

    2016-08-15

    The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation.

  17. Glutamate transporter-associated anion channels adjust intracellular chloride concentrations during glial maturation.

    PubMed

    Untiet, Verena; Kovermann, Peter; Gerkau, Niklas J; Gensch, Thomas; Rose, Christine R; Fahlke, Christoph

    2017-02-01

    Astrocytic volume regulation and neurotransmitter uptake are critically dependent on the intracellular anion concentration, but little is known about the mechanisms controlling internal anion homeostasis in these cells. Here we used fluorescence lifetime imaging microscopy (FLIM) with the chloride-sensitive dye MQAE to measure intracellular chloride concentrations in murine Bergmann glial cells in acute cerebellar slices. We found Bergmann glial [Cl(-) ]int to be controlled by two opposing transport processes: chloride is actively accumulated by the Na(+) -K(+) -2Cl(-) cotransporter NKCC1, and chloride efflux through anion channels associated with excitatory amino acid transporters (EAATs) reduces [Cl(-) ]int to values that vary upon changes in expression levels or activity of these channels. EAATs transiently form anion-selective channels during glutamate transport, and thus represent a class of ligand-gated anion channels. Age-dependent upregulation of EAATs results in a developmental chloride switch from high internal chloride concentrations (51.6 ± 2.2 mM, mean ± 95% confidence interval) during early development to adult levels (35.3 ± 0.3 mM). Simultaneous blockade of EAAT1/GLAST and EAAT2/GLT-1 increased [Cl(-) ]int in adult glia to neonatal values. Moreover, EAAT activation by synaptic stimulations rapidly decreased [Cl(-) ]int . Other tested chloride channels or chloride transporters do not contribute to [Cl(-) ]int under our experimental conditions. Neither genetic removal of ClC-2 nor pharmacological block of K(+) -Cl(-) cotransporter change resting Bergmann glial [Cl(-) ]int in acute cerebellar slices. We conclude that EAAT anion channels play an important and unexpected role in adjusting glial intracellular anion concentration during maturation and in response to cerebellar activity. GLIA 2017;65:388-400.

  18. A Hypoxia-Responsive Glial Cell–Specific Gene Therapy Vector for Targeting Retinal Neovascularization

    PubMed Central

    Biswal, Manas R.; Prentice, Howard M.; Dorey, C. Kathleen; Blanks, Janet C.

    2014-01-01

    Purpose. Müller cells, the major glial cell in the retina, play a significant role in retinal neovascularization in response to tissue hypoxia. We previously designed and tested a vector using a hypoxia-responsive domain and a glial fibrillary acidic protein (GFAP) promoter to drive green fluorescent protein (GFP) expression in Müller cells in the murine model of oxygen-induced retinopathy (OIR). This study compares the efficacy of regulated and unregulated Müller cell delivery of endostatin in preventing neovascularization in the OIR model. Methods. Endostatin cDNA was cloned into plasmids with hypoxia-regulated GFAP or unregulated GFAP promoters, and packaged into self-complementary adeno-associated virus serotype 2 vectors (scAAV2). Before placement in hyperoxia on postnatal day (P)7, mice were given intravitreal injections of regulated or unregulated scAAV2, capsid, or PBS. Five days after return to room air, on P17, neovascular and avascular areas, as well as expression of the transgene and vascular endothelial growth factor (VEGF), were compared in OIR animals treated with a vector, capsid, or PBS. Results. The hypoxia-regulated, glial-specific, vector-expressing endostatin reduced neovascularization by 93% and reduced the central vaso-obliteration area by 90%, matching the results with the unregulated GFAP-Endo vector. Retinas treated with the regulated endostatin vector expressed substantial amounts of endostatin protein, and significantly reduced VEGF protein. Endostatin production from the regulated vector was undetectable in retinas with undamaged vasculature. Conclusions. These findings suggest that the hypoxia-regulated, glial cell–specific vector expressing endostatin may be useful for treatment of neovascularization in proliferative diabetic retinopathy. PMID:25377223

  19. Brain Rewarding Stimulation Reduces Extracellular Glutamate Through Glial Modulation in Medial Prefrontal Cortex of Rats.

    PubMed

    Murakami, Gen; Nakamura, Masato; Takita, Masatoshi; Ishida, Yasushi; Ueki, Takatoshi; Nakahara, Daiichiro

    2015-11-01

    Growing evidence implicates a critical involvement of prefrontal glial modulation of extracellular glutamate (GLU) in aversive behaviors. However, nothing is known about whether prefrontal glial cells modulate GLU levels in rewarding behaviors. To address this question, we measured GLU efflux in the medial prefrontal cortex (PFC) of rats associated with rewarding behaviors. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) as the rewarding behavior. GLU was indirectly measured using microdialysis combined with on-line fluorometric detection of NADH resulting from the reaction of GLU and NAD(+) catalyzed by GLU dehydrogenase with a time resolution of 1 min. ICSS caused a minute-by-minute change of extracellular GLU in the medial PFC, with a slight decrease during the stimulation, followed by an increase afterward. This bidirectional change was tetrodotoxin insensitive and abolished by the gliotoxin fluorocitrate. To confirm and extend the previous studies of aversion-induced increase of extracellular GLU in the medial PFC, we also measured prefrontal GLU efflux associated with an aversive stimulation, immobilization stress. The temporal change in extracellular GLU caused by this stress was markedly different from that observed during ICSS. A rapid increase in GLU was detected during the aversive stimulation, followed by a large increase afterward. This bimodal change was tetrodotoxin insensitive, similar to that detected for ICSS. These findings indicate a bidirectional regulation of extracellular GLU by prefrontal glial cells associated with rat ICSS behavior, and reveal that glial modulation of GLU neurochemistry in the medial PFC contributes to rewarding as well as aversive behaviors in rats.

  20. Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture

    PubMed Central

    Li, Wen-Wu; Guo, Tian-Zhi; Shi, Xiaoyou; Sun, Yuan; Wei, Tzuping; Clark, David J; Kingery, Wade S

    2015-01-01

    Tibia fracture in rodents induces substance P (SP)-dependent keratinocyte activation and inflammatory changes in the hindlimb, similar to those seen in complex regional pain syndrome (CRPS). In animal pain models spinal glial cell activation results in nociceptive sensitization. This study tested the hypothesis that limb fracture triggers afferent C-fiber SP release in the dorsal horn, resulting in chronic glia activation and central sensitization. At 4 weeks after tibia fracture and casting in rats, the cast was removed and hind paw allodynia, unweighting, warmth, and edema were measured, then the antinociceptive effects of microglia (minocycline) or astrocyte (LAA) inhibitors or an SP receptor antagonist (LY303870) were tested. Immunohistochemistry and PCR were used to evaluate microglia and astrocyte activation in the dorsal horn. Similar experiments were performed in intact rats after brief sciatic nerve electric stimulation at C-fiber intensity. Microglia and astrocytes were chronically activated at 4 weeks after fracture and contributed to the maintenance of hind paw allodynia and unweighting. Furthermore, LY303870 treatment initiated at 4 weeks after fracture partially reversed both spinal glial activation and nociceptive sensitization. Similarly, persistent spinal microglial activation and hind paw nociceptive sensitization were observed at 48 hours after sciatic nerve C-fiber stimulation and this effect was inhibited by treatment with minocycline, LAA, or LY303870. These data support the hypothesis that C-fiber afferent SP signaling chronically supports spinal neuroglia activation after limb fracture and that glial activation contributes to the maintenance of central nociceptive sensitization in CRPS. Treatments inhibiting glial activation and spinal inflammation may be therapeutic for CRPS. PMID:26386297

  1. Improved visualization of neuronal injury following glial activation by manganese enhanced MRI.

    PubMed

    Bade, Aditya N; Zhou, Biyun; Epstein, Adrian A; Gorantla, Santhi; Poluektova, Larisa Y; Luo, Jiangtao; Gendelman, Howard E; Boska, Michael D; Liu, Yutong

    2013-09-01

    Research directed at anatomical, integrative and functional activities of the central nervous system (CNS) can be realized through bioimaging. A wealth of data now demonstrates the utility of magnetic resonance imaging (MRI) towards unraveling complex neural connectivity operative in health and disease. A means to improve MRI sensitivity is through contrast agents and notably manganese (Mn²⁺). The Mn²⁺ ions enter neurons through voltage-gated calcium channels and unlike other contrast agents such as gadolinium, iron oxide, iron platinum and imaging proteins, provide unique insights into brain physiology. Nonetheless, a critical question that remains is the brain target cells serving as sources for the signal of Mn²⁺ enhanced MRI (MEMRI). To this end, we investigated MEMRI's abilities to detect glial (astrocyte and microglia) and neuronal activation signals following treatment with known inflammatory inducing agents. The idea is to distinguish between gliosis (glial activation) and neuronal injury for the MEMRI signal and as such use the agent as a marker for neural activity in inflammatory and degenerative disease. We now demonstrate that glial inflammation facilitates Mn²⁺ neuronal ion uptake. Glial Mn²⁺ content was not linked to its activation. MEMRI performed on mice injected intracranially with lipopolysaccharide was associated with increased neuronal activity. These results support the notion that MEMRI reflects neuronal excitotoxicity and impairment that can occur through a range of insults including neuroinflammation. We conclude that the MEMRI signal enhancement is induced by inflammation stimulating neuronal Mn²⁺ uptake.

  2. Glial Fibrillary Acidic Protein-Expressing Glia in the Mouse Lung

    PubMed Central

    Suarez-Mier, Gabriela B.

    2015-01-01

    Autonomic nerves regulate important functions in visceral organs, including the lung. The postganglionic portion of these nerves is ensheathed by glial cells known as non-myelinating Schwann cells. In the brain, glia play important functional roles in neurotransmission, neuroinflammation, and maintenance of the blood brain barrier. Similarly, enteric glia are now known to have analogous roles in gastrointestinal neurotransmission, inflammatory response, and barrier formation. In contrast to this, very little is known about the function of glia in other visceral organs. Like the gut, the lung forms a barrier between airborne pathogens and the bloodstream, and autonomic lung innervation is known to affect pulmonary inflammation and lung function. Lung glia are described as non-myelinating Schwann cells but their function is not known, and indeed no transgenic tools have been validated to study them in vivo. The primary goal of this research was, therefore, to investigate the relationship between non-myelinating Schwann cells and pulmonary nerves in the airways and vasculature and to validate existing transgenic mouse tools that would be useful for studying their function. We focused on the glial fibrillary acidic protein promoter, which is a cognate marker of astrocytes that is expressed by enteric glia and non-myelinating Schwann cells. We describe the morphology of non-myelinating Schwann cells in the lung and verify that they express glial fibrillary acidic protein and S100, a classic glial marker. Furthermore, we characterize the relationship of non-myelinating Schwann cells to pulmonary nerves. Finally, we report tools for studying their function, including a commercially available transgenic mouse line. PMID:26442852

  3. Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

    NASA Astrophysics Data System (ADS)

    Brew, Helen; Attwell, David

    1987-06-01

    Glutamate is taken up avidly by glial cells in the central nervous system1. Glutamate uptake may terminate the transmitter action of glutamate released from neurons1, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique2. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

  4. Stereological Analysis of Neuron, Glial and Endothelial Cell Numbers in the Human Amygdaloid Complex

    PubMed Central

    García-Amado, María; Prensa, Lucía

    2012-01-01

    Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm3 and mean cell numbers (x106) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals’ age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions. PMID:22719923

  5. Dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of monoarthritis

    PubMed Central

    Xu, Bo; Zhang, Wei-shi; Yang, Jia-le; Xu, Hua; Deng, Xiao-ming; Zhang, Yu-qiu

    2010-01-01

    Aim: To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (α2AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis (MA). Methods: MA was induced by an intra-articular injection of complete Freund's adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting. Results: Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 μg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 μg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. Conclusion: Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats. PMID:20364156

  6. Eccentric Exercise Leads to Glial Activation but not Apoptosis in Mice Spinal Cords.

    PubMed

    Pereira, B C; Lucas, G; da Rocha, A L; Pauli, J R; Ropelle, E R; Cintra, D; de Souza, C T; Bueno, C R; da Silva, A S

    2015-05-01

    The aim of this investigation was to evaluate the effects of 3 overtraining (OT) protocols on the glial activation and apoptosis in the spinal cords of mice. Rodents were divided into control (C; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR). The incremental load test, ambulation test, exhaustive test and functional behavioural assessment were used as performance evaluation parameters. 36 h after the exhaustive test, the dorsal and ventral parts of the lumbar spinal cord (L4-L6) were dissected for subsequent protein analysis by immunoblotting. The OT protocols led to similar responses of some performance parameters. The ventral glial fibrillary acidic protein (GFAP) protein levels were diminished in the OTR/up and OTR compared to CT and OTR/down groups. The ventral ionized calcium binding adaptor molecule 1 (Iba-1), and the dorsal GFAP and Iba-1 protein levels were increased in the OTR/down compared to the other groups. The ratio between the cleaved capase-3/caspase-3 and cleaved caspase-9/caspase-9 measured in the spinal cord were not sensitive to the OT protocols. In summary, the OTR/down activated the glial cells in the motor (i. e. Iba-1) and sensory (i. e. GFAP and Iba-1) neurons without leading to apoptosis.

  7. Glial abnormalities in substance use disorders and depression: Does shared glutamatergic dysfunction contribute to comorbidity?

    PubMed Central

    Niciu, Mark J.; Henter, Ioline D.; Sanacora, Gerard; Zarate, Carlos A.

    2014-01-01

    Objectives Preclinical and clinical research in neuropsychiatric disorders, particularly mood and substance use disorders, have historically focused on neurons; however, glial cells – astrocytes, microglia, and oligodendrocytes – also play key roles in these disorders. Methods Peer-reviewed PubMed/Medline articles published through December 2012 were identified using the following keyword combinations: glia, astrocytes, oligodendrocytes/glia, microglia, substance use, substance abuse, substance dependence, alcohol, opiate, opioid, cocaine, psychostimulants, stimulants, and glutamate. Results Depressive and substance use disorders are highly comorbid, suggesting a common or overlapping aetiology and pathophysiology. Reduced astrocyte cell number occurs in both disorders. Altered glutamate neurotransmission and metabolism – specifically changes in the levels/activity of transporters, receptors, and synaptic proteins potentially related to synaptic physiology – appear to be salient features of both disorders. Glial cell pathology may also underlie the pathophysiology of both disorders via impaired astrocytic production of neurotrophic factors. Microglial/neuroinflammatory pathology is also evident in both depressive and substance use disorders. Finally, oligodendrocyte impairment decreases myelination and impairs expression of myelin-related genes in both substance use and depressive disorders. Conclusions Glial-mediated glutamatergic dysfunction is a common neuropathological pathway in both substance use and depression. Therefore, glutamatergic neuromodulation is a rational drug target in this comorbidity. PMID:24024876

  8. Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of Glial Lineage

    PubMed Central

    Able, Richard A.; Ngnabeuye, Celestin; Beck, Cade; Holland, Eric C.; Vazquez, Maribel

    2013-01-01

    Glial tumors have demonstrated abilities to sustain growth via recruitment of glial progenitor cells (GPCs), which is believed to be driven by chemotactic cues. Previous studies have illustrated that mouse GPCs of different genetic backgrounds are able to replicate the dispersion pattern seen in the human disease. How GPCs with genetic backgrounds transformed by tumor paracrine signaling respond to extracellular cues via migration is largely unexplored, and remains a limiting factor in utilizing GPCs as therapeutic targets. In this study, we utilized a microfluidic device to examine the chemotaxis of three genetically-altered mouse GPC populations towards tumor conditioned media, as well as towards three growth factors known to initiate the chemotaxis of cells excised from glial tumors: Hepatocyte Growth Factor (HGF), Platelet-Derived Growth Factor-BB (PDGF-BB), and Transforming Growth Factor-α (TGF-α). Our results illustrate that GPC types studied exhibited chemoattraction and chemorepulsion by different concentrations of the same ligand, as well as enhanced migration in the presence of ultra-low ligand concentrations within environments of high concentration gradient. These findings contribute towards our understanding of the causative and supportive roles that GPCs play in tumor growth and reoccurrence, and also point to GPCs as potential therapeutic targets for glioma treatment. PMID:24285985

  9. Satellite glial cells in dorsal root ganglia are activated in streptozotocin-treated rodents.

    PubMed

    Hanani, Menachem; Blum, Erez; Liu, Shuangmei; Peng, Lichao; Liang, Shangdong

    2014-12-01

    Neuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pain types, and we investigated what are the changes that satellite glial cells (SGCs) in dorsal root ganglia undergo in a DM type 1 model, induced by streptozotocin (STZ) in mice and rats. We carried out immunohistochemical studies to learn about changes in the activation marker glial fibrillary acidic protein (GFAP) in SGCs. We found that after STZ-treatment the number of neurons surrounded with GFAP-positive SGCs in dorsal root ganglia increased 4-fold in mice and 5-fold in rats. Western blotting for GFAP, which was done only on rats because of the larger size of the ganglia, showed an increase of about 2-fold in STZ-treated rats, supporting the immunohistochemical results. These results indicate for the first time that SGCs are activated in rodent models of DM1. As SGC activation appears to contribute to chronic pain, these results suggest that SGCs may participate in the generation and maintenance of diabetic neuropathic pain, and can serve as a potential therapeutic target.

  10. Numerical modelling and in vivo analysis of fluorescent and laser light backscattered from glial brain tumors

    NASA Astrophysics Data System (ADS)

    Savelieva, Tatiana A.; Kalyagina, Nina A.; Kholodtsova, Maria N.; Loschenov, Victor B.; Goryainov, Sergey A.; Potapov, Aleksander A.

    2012-03-01

    Brain glial tumors have peculiar features of the perifocal region extension, characterized by its indistinct area, which complicates determination of the borders for tissue resection. In the present study filter-reduced back-scattered laser light signals, compared to the data from mathematical modeling, were used for description of the brain white matter. The simulations of the scattered light distributions were performed in a Monte Carlo program using scattering and absorption parameters of the different grades of the brain glial tumors. The parameters were obtained by the Mie calculations for three main types of scatterers: myelinated axon fibers, cell nuclei and mitochondria. It was revealed that diffuse-reflected light, measured at the perifocal areas of the glial brain tumors, shows a significant difference relative to the signal, measured at the normal tissue, which signifies the possibility to provide diagnostically useful information on the tissue state, and to determine the borders of the tumor, thus to reduce the recurrence appearance. Differences in the values of ratios of diffuse reflectance from active growth parts of tumors and normal white matter can be useful for determination of the degree of tumor progress during the spectroscopic analysis.

  11. Comparative study of human neuronal and glial cell sensitivity for in vitro neurogenotoxicity testing.

    PubMed

    Laffon, Blanca; Fernández-Bertólez, Natalia; Costa, Carla; Pásaro, Eduardo; Valdiglesias, Vanessa

    2017-04-01

    Cell cultures from neuronal and glial origin have proven to be powerful tools for elucidating cellular and molecular mechanisms of nervous system development and physiology, and as neurotoxicity models to evaluate in vitro the possible effects of chemicals. But cellular heterogeneity of nervous system is considerable and these cells have been shown to respond diversely to neurotoxic insults, leading to disparate results from different studies. To shed more light on suitability of cellular models of nervous origin for neurotoxicity screening, the objective of this study was to compare the sensitivity to genetic damage induction of two nervous cell lines. To this aim, neurons (SH-SY5Y) and glial (A172) cells were treated with differently-acting genotoxic agents (bleomycin, actinomycin-D, methyl methanesulfonate, mitomycin C, and griseofulvin). After discarding cytotoxicity, genotoxicity was evaluated by a battery of assays encompassing detection of different genetic lesions. Results obtained showed that glial cells are generally more resistant to genotoxic damage induced by clastogenic agents, but more sensitive to aneugenic effects. These results highlight the need of proper design of in vitro neurotoxicology studies, especially for neurogenotoxicity screening, emphasizing the importance of employing more than one nervous cell type for testing the potential toxicity of a particular exposure.

  12. Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases

    PubMed Central

    Ochoa-Cortes, Fernando; Turco, Fabio; Linan-Rico, Andromeda; Soghomonyan, Suren; Whitaker, Emmett; Wehner, Sven; Cuomo, Rosario

    2015-01-01

    Abstract: The word “glia” is derived from the Greek word “γλοια,” glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the “reactive glial phenotype” is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor–α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential. PMID:26689598

  13. Counter-regulation of opioid analgesia by glial-derived bioactive sphingolipids

    PubMed Central

    Muscoli, Carolina; Doyle, Tim; Dagostino, Concetta; Bryant, Leesa; Chen, Zhoumou; Watkins, Linda R.; Ryerse, Jan; Bieberich, Erhard; Neumman, William; Salvemini, Daniela

    2010-01-01

    The clinical efficacy of opiates for pain control is severely limited by analgesic tolerance and hyperalgesia. Herein we show that chronic morphine upregulates both the sphingolipid ceramide in spinal astrocytes and microglia, but not neurons, and spinal sphingosine-1-phosphate (S1P), the end-product of ceramide metabolism. Co-administering morphine with intrathecal administration of pharmacological inhibitors of ceramide and S1P blocked formation of spinal S1P and development of hyperalgesia and tolerance in rats. Our results show that spinally formed S1P signals at least in part by 1) modulating glial function, since inhibiting S1P formation blocked increased formation of glial-related pro-inflammatory cytokines, in particular TNF-α, IL-1β α, and IL6, which are known modulators of neuronal excitability, and 2) peroxynitrite-mediated post-translational nitration and inactivation of glial-related enzymes (glutamine synthetase and the glutamate transporter, GLT-1) known to play critical roles in glutamate neurotransmission. Inhibitors of the ceramide metabolic pathway may have therapeutic potential as adjuncts to opiates in relieving suffering from chronic pain. PMID:21084596

  14. Spinal Cord Injury Impairs Neurogenesis and Induces Glial Reactivity in the Hippocampus.

    PubMed

    Jure, Ignacio; Pietranera, Luciana; De Nicola, Alejandro F; Labombarda, Florencia

    2017-03-13

    The incorporation of newborn neurons with increased synaptic remodeling and activity-dependent plasticity in the dentate gyrus enhances hippocampal-dependent learning performances. Astrocytes and microglial cells are components of the neurogenic niche and regulate neurogenesis under normal and neurophatological conditions leading to functional consequences for learning and memory. Although cognitive impairments were reported in patients after spinal cord injury (SCI), only few studies have considered remote changes in brain structures which are not related with sensory and motor cortex. Thus, we examined neurogenesis and glial reactivity by stereological assessment in dentate gyrus sub-regions after three different intensities of thoracic spinal cord compression in rats. Sixty days after injury we observed a decrease in the Basso-Bresnahan-Beattie locomotor scale scores, rotarod performance and volume of spare tissue that correlated with the severity of the compression. Regarding the hippocampus, we observed that neurogenesis and hilar neurons were reduced after severe SCI, while only neurogenesis decreased in the moderately injured group. In addition, severe SCI induced reactive microglia and astrogliosis in all dentate gyrus sub-regions. Furthermore, the density of reactive microglia increased in the hilus whereas astrogliosis developed in the molecular layer after moderate SCI. No changes were observed in the mildly injured rats. These results suggest glial response and neurogenesis are associated with injury intensity. Interestingly, hippocampal neurogenesis is more sensitive to SCI than astrocytes or microglia reaction, as moderate injury impairs the generation of new neurons without changing glial response in the subgranular zone.

  15. Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells.

    PubMed

    Huerta-García, Elizabeth; Pérez-Arizti, José Antonio; Márquez-Ramírez, Sandra Gissela; Delgado-Buenrostro, Norma Laura; Chirino, Yolanda Irasema; Iglesias, Gisela Gutiérrez; López-Marure, Rebeca

    2014-08-01

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used in the chemical, electrical, and electronic industries. TiO2 NPs can enter directly into the brain through the olfactory bulb and can be deposited in the hippocampus region; therefore, we determined the toxic effect of TiO2 NPs on rat and human glial cells, C6 and U373, respectively. We evaluated some events related to oxidative stress: (1) redox-signaling mechanisms by oxidation of 2',7'-dichlorodihydrofluorescein diacetate; (2) peroxidation of lipids by cis-parinaric acid; (3) antioxidant enzyme expression by PCR in real time; and (4) mitochondrial damage by MitoTracker Green FM staining and Rh123. TiO2 NPs induced a strong oxidative stress in both glial cell lines by mediating changes in the cellular redox state and lipid peroxidation associated with a rise in the expression of glutathione peroxidase, catalase, and superoxide dismutase 2. TiO2 NPs also produced morphological changes, damage of mitochondria, and an increase in mitochondrial membrane potential, indicating toxicity. TiO2 NPs had a cytotoxic effect on glial cells; however, more in vitro and in vivo studies are required to ascertain that exposure to TiO2 NPs can cause brain injury and be hazardous to health.

  16. The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice

    PubMed Central

    Weidemann, Alexander; Kerdiles, Yann M.; Knaup, Karl X.; Rafie, Christopher A.; Boutin, Adam T.; Stockmann, Christian; Takeda, Norihiko; Scadeng, Miriam; Shih, Andy Y.; Haase, Volker H.; Simon, M. Celeste; Kleinfeld, David; Johnson, Randall S.

    2009-01-01

    A key adaptation to environmental hypoxia is an increase in erythropoiesis, driven by the hormone erythropoietin (EPO) through what is traditionally thought to be primarily a renal response. However, both neurons and astrocytes (the largest subpopulation of glial cells in the CNS) also express EPO following ischemic injury, and this response is known to ameliorate damage to the brain. To investigate the role of glial cells as a component of the systemic response to hypoxia, we created astrocyte-specific deletions of the murine genes encoding the hypoxia-inducible transcription factors HIF-1α and HIF-2α and their negative regulator von Hippel–Lindau (VHL) as well as astrocyte-specific deletion of the HIF target gene Vegf. We found that loss of the hypoxic response in astrocytes does not cause anemia in mice but is necessary for approximately 50% of the acute erythropoietic response to hypoxic stress. In accord with this, erythroid progenitor cells and reticulocytes were substantially reduced in number in mice lacking HIF function in astrocytes following hypoxic stress. Thus, we have demonstrated that the glial component of the CNS is an essential component of hypoxia-induced erythropoiesis. PMID:19809162

  17. Glial differentiation in the germinal layer of fetal and preterm infant brain: an immunocytochemical study.

    PubMed

    Gould, S J; Howard, S

    1988-01-01

    The germinal layer in preterm infants is a common site of intracerebral hemorrhage that is associated with increased mortality and morbidity in survivors. This matrix is composed of a mass of immature cells containing many thin-walled blood vessels. A major factor in the occurrence of hemorrhage at this site is the absence of a network of fibers to support these vessels. This immunocytochemical study has examined glial differentiation within the germinal layer of brains from fetuses and preterm infants of gestational ages 18 to 35 weeks. Progressive glial differentiation with gestation is described. This process is not uniform and the more posterior germinal layer, lying over the body of the caudate nucleus, demonstrates more rapid maturation than that lying anteriorly near the head of the caudate nucleus. Anteriorly, even at 35 weeks of gestation, a central core of germinal layer cells remains immature with little evidence of glial differentiation. These changes may be related to the occurrence and distribution of germinal layer hemorrhages in preterm infants of varying gestations.

  18. Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex.

    PubMed

    García-Amado, María; Prensa, Lucía

    2012-01-01

    Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3) and mean cell numbers (x10(6)) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.

  19. γ-Aminobutyric acid-ρ expression in ependymal glial cells of the mouse cerebellum.

    PubMed

    Reyes-Haro, Daniel; González-González, María Alejandra; Pétriz, Adriana; Rosas-Arellano, Abraham; Kettenmann, Helmut; Miledi, Ricardo; Martínez-Torres, Ataulfo

    2013-04-01

    The ependymal glial cells (EGCs) from the periventricular zone of the cerebellum were studied to determine their distribution and the functional properties of their γ-aminobutyric acid type A (GABA(A) ) receptors. EGCs were identified by the presence of ciliated structures on their ventricular surface and their expression of glial fibrillary acidic protein (GFAP). Interestingly, diverse cell types, including neurons, astrocytes, and other types of glia, were identified in the subventricular zone by their current profiles. Electron microscopy showed ciliated cells and myelinated axons in this zone, but we found no collateral connections to suggest the presence of functional synapses. GABA-mediated currents were recorded from EGCs in cerebellar slices from postnatal days 13 to 35 (PN13-PN35). These currents were blocked by TPMPA (a highly specific GABA(A) ρ subunit antagonist) and bicuculline (a selective antagonist for classic GABA(A) receptors). Pentobarbital failed to modulate GABA(A)-mediated currents despite the expression of GABAα1 and GABAγ2 subunits. In situ hybridization, RT-PCR, and immunofluorescence studies confirmed GABAρ1 expression in EGCs of the cerebellum. We conclude that cerebellar EGCs express GABAρ1, which is functionally involved in GABA(A) receptor-mediated responses that are unique among glial cells of the brain.

  20. Enteric glial reactivity to systemic LPS administration: Changes in GFAP and S100B protein.

    PubMed

    da Cunha Franceschi, Raphaela; Nardin, Patrícia; Machado, Clivia Valle; Tortorelli, Lucas Silva; Martinez-Pereira, Malcon Andrei; Zanotto, Caroline; Gonçalves, Carlos-Alberto; Zancan, Denise Maria

    2017-01-04

    Lipopolysaccharide (LPS) is used to induce inflammation and promotes nervous system activation. Different regions of the brain present heterogeneous glial responses; thus, in order to verify whether systemic LPS-induced inflammation affects the enteric glia differently across the intestinal segments, we evaluated the expressions of two glial activity markers, GFAP and S100B protein, in different intestine segments, at 1h, 24h and 7days after acute systemic LPS administration (0.25 or 2.5mgkg(-1)) in rats. Histological inflammatory analysis indicated that the cecum was most affected when compared to the duodenum and proximal colon at the highest doses of LPS. LPS induced an increased S100B content after 24h in all three regions, which decreased at 7days after the highest dose in all regions. Moreover, at 24h, this dose of LPS increased ex-vivo S100B secretion only in the cecum. The highest dose of LPS also increased GFAP in all regions at 24h, but earlier in the cecum, where LPS-induced enteric S100B and GFAP alterations were dependent on dose, time and intestine region. No associated changes in serum S100B were observed. Our results indicate heterogeneous enteric glial responses to inflammatory insult, as observed in distinct brain areas.

  1. Myelinating satellite oligodendrocytes are integrated in a glial syncytium constraining neuronal high-frequency activity

    PubMed Central

    Battefeld, Arne; Klooster, Jan; Kole, Maarten H. P.

    2016-01-01

    Satellite oligodendrocytes (s-OLs) are closely apposed to the soma of neocortical layer 5 pyramidal neurons but their properties and functional roles remain unresolved. Here we show that s-OLs form compact myelin and action potentials of the host neuron evoke precisely timed Ba2+-sensitive K+ inward rectifying (Kir) currents in the s-OL. Unexpectedly, the glial K+ inward current does not require oligodendrocytic Kir4.1. Action potential-evoked Kir currents are in part mediated by gap–junction coupling with neighbouring OLs and astrocytes that form a syncytium around the pyramidal cell body. Computational modelling predicts that glial Kir constrains the perisomatic [K+]o increase most importantly during high-frequency action potentials. Consistent with these predictions neurons with s-OLs showed a reduced probability for action potential burst firing during [K+]o elevations. These data suggest that s-OLs are integrated into a glial syncytium for the millisecond rapid K+ uptake limiting activity-dependent [K+]o increase in the perisomatic neuron domain. PMID:27161034

  2. Chromatin remodeling during the in vivo glial differentiation in early Drosophila embryos

    PubMed Central

    Ye, Youqiong; Gu, Liang; Chen, Xiaolong; Shi, Jiejun; Zhang, Xiaobai; Jiang, Cizhong

    2016-01-01

    Chromatin remodeling plays a critical role in gene regulation and impacts many biological processes. However, little is known about the relationship between chromatin remodeling dynamics and in vivo cell lineage commitment. Here, we reveal the patterns of histone modification change and nucleosome positioning dynamics and their epigenetic regulatory roles during the in vivo glial differentiation in early Drosophila embryos. The genome-wide average H3K9ac signals in promoter regions are decreased in the glial cells compared to the neural progenitor cells. However, H3K9ac signals are increased in a group of genes that are up-regulated in glial cells and involved in gliogenesis. There occurs extensive nucleosome remodeling including shift, loss, and gain. Nucleosome depletion regions (NDRs) form in both promoters and enhancers. As a result, the associated genes are up-regulated. Intriguingly, NDRs form in two fashions: nucleosome shift and eviction. Moreover, the mode of NDR formation is independent of the original chromatin state of enhancers in the neural progenitor cells. PMID:27634414

  3. Molecular and immunocytochemical characterization of primary neuronal cultures from adult rat brain: Differential expression of neuronal and glial protein markers.

    PubMed

    Ray, Balmiki; Bailey, Jason A; Sarkar, Sumit; Lahiri, Debomoy K

    2009-11-15

    Neurobiological studies using primary neuronal cultures commonly employ fetal-derived neurons, but much less often adult brain-derived neurons. Our goal is to perform morphological and molecular characterization of primary neuronal cultures from adult rat brain, including the relative expression of neuronal and glial cell markers at different time points. We tested the hypothesis that long-term neuronal viability is compatible with glial proliferation in adult neuron culture. We examined neuron culture from adult rat brain, which was maintained at steady state up to 24 days, and characterized them on the basis of cellular, molecular and biochemical properties at different time points of the culture. We identified neuronal and glial cells by both immunocytochemical and western immunoblotting techniques using NSE and Tau as neuronal markers and GFAP as glial protein marker, which revealed the presence of predominantly neuronal cells in the initial phase of the culture and a rise in glial cells from day 12 onwards. Notably, neuronal cells were preserved in the culture along with the glial cells even at day 24. Transfection of the cultured cells with a GFP expression vector and plasmids containing a luciferase reporter gene under the control of two different gene promoters demonstrated DNA transfectability. Taken together, these results suggest a differential expression of neuronal and glial cells at different time points and long-term neuronal viability in the presence of glial proliferation. Such adult neurons serve as a suitable system for the application of neurodegeneration models and for drug target discovery in various brain disorders including Alzheimer's disease.

  4. Immunocytochemical localization of glial fibrillary acidic protein (GFAP) in the area postrema of the cat - Light and electron microscopic study

    NASA Technical Reports Server (NTRS)

    Damelio, F. E.; Gibbs, M. A.; Mehler, W. R.; Eng, L. F.

    1985-01-01

    Glial fibrillary acidic protein (GFAP) was demonstrated in the cytoplasm and processes of ependymal cells and astroglial components of the area postrema of the cat. These observations differ from the findings in the ependyma of the ventricular cavities which are consistently negative for the protein. Since some studies have suggested sensory functions of the glial cells in this emetic chemoreceptor trigger zone, a careful consideration of morphological and biochemical attributes of these cells seems appropriate.

  5. Stress Changes the Spatial Arrangement of Neurons and Glial Cells of Medial Prefrontal Cortex and Sertraline and Curcumin Prevent It

    PubMed Central

    Noorafshan, Ali; Abdollahifar, Mohammad-Amin

    2015-01-01

    Objective The present study explored the three-dimensional spatial arrangements of the neurons and glial cells within the medial prefrontal cortex (mPFC) of rats. Methods It evaluated the arrangement for differences after stress with or without treatment with curcumin and sertraline using second-order stereology. Orientator method was applied to obtain isotropic uniform random sections of mPFC. The pair correlation g(r) and cross-correlation functions were estimated by counting dipole probes superimposed on histological sections of mPFC. Results The mean total volume of neurons and glial cells was 0.80 (0.05) and 0.40 (0.07), respectively in the control group. The corresponding values decreased by 50% in the stressed group. The curve of g(r) for the neurons and glial cells showed a wider gap between the stressed rats' mPFC. Theses indicate a negative correlation (repulsion) between the neurons and glial cells in the stressed rats. Evaluation of the cross-correlation function of the neurons and glial cells also showed a negative correlation in the stressed group. The estimated values of the global degree of order in the spatial point pattern for neurons and glial cells were 0.62 and 0.20 in control and stressed animals, respectively. Curcumin and sertraline protected the spatial arrangements of the cells after stress induction in rats. In addition, the volume of the neurons and glial cells remained unchanged after stress. Conclusion Dissociation of the neurons and glial cells can is seen at some places in the stressed rats' cortex. However, the spatial arrangement of the cells was remained unchanged in curcumin+stress and sertraline+stress rats. PMID:25670949

  6. 17 CFR 39.7 - Fraud in connection with the clearing of transactions on a derivatives clearing organization.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... clearing of transactions on a derivatives clearing organization. 39.7 Section 39.7 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES CLEARING ORGANIZATIONS § 39.7 Fraud in connection with the clearing of transactions on a derivatives clearing organization. It shall be unlawful for...

  7. MODIS Collection 6 Clear Sky Restoral (CSR): Filtering Cloud Mast 'Not Clear' Pixels

    NASA Technical Reports Server (NTRS)

    Meyer, Kerry G.; Platnick, Steven Edward; Wind, Galina; Riedi, Jerome

    2014-01-01

    Correctly identifying cloudy pixels appropriate for the MOD06 cloud optical and microphysical property retrievals is accomplished in large part using results from the MOD35 1km cloud mask tests (note there are also two 250m subpixel cloud mask tests that can convert the 1km cloudy designations to clear sky). However, because MOD35 is by design clear sky conservative (i.e., it identifies "not clear" pixels), certain situations exist in which pixels identified by MOD35 as "cloudy" are nevertheless likely to be poor retrieval candidates. For instance, near the edge of clouds or within broken cloud fields, a given 1km MODIS field of view (FOV) may in fact only be partially cloudy. This can be problematic for the MOD06 retrievals because in these cases the assumptions of a completely overcast homogenous cloudy FOV and 1-dimensional plane-parallel radiative transfer no longer hold, and subsequent retrievals will be of low confidence. Furthermore, some pixels may be identified by MOD35 as "cloudy" for reasons other than the presence of clouds, such as scenes with thick smoke or lofted dust, and should therefore not be retrieved as clouds. With such situations in mind, a Clear Sky Restoral (CSR) algorithm was introduced in C5 that attempts to identify pixels expected to be poor retrieval candidates. Table 1 provides SDS locations for CSR and partly cloudy (PCL) pixels.

  8. Clear cell renal cell tumors: Not all that is "clear" is cancer.

    PubMed

    Williamson, Sean R; Cheng, Liang

    2016-07-01

    Continued improvement of our understanding of the clinical, histologic, and genetic features of renal cell tumors has progressively evolved renal tumor classification, revealing an expanding array of distinct tumor types with different implications for prognosis, patient counseling, and treatment. Although clear cell renal cell carcinoma is unequivocally the most common adult renal tumor, there is growing evidence that some "clear cell" renal neoplasms, such as exemplified by multilocular cystic clear cell renal neoplasm of low malignant potential (formerly multilocular cystic renal cell carcinoma), do not have the same potential for insidious progression and metastasis, warranting reclassification as low malignant potential tumors or benign neoplasms. Still other novel tumor types such as clear cell papillary renal cell carcinoma have been more recently recognized, which similarly have shown a conspicuous absence of aggressive behavior to date, suggesting that these too may be recategorized as noncancerous or may be premalignant neoplasms. This importance for prognosis is increasingly significant in the modern era, in which renal masses are increasingly found incidentally by imaging techniques at a small tumor size, raising consideration for less aggressive management options guided by renal mass biopsy diagnosis, including imaging surveillance, tumor ablation, or partial nephrectomy.

  9. When a Cleared Rape Is Not Cleared: A Multilevel Study of Arrest and Exceptional Clearance.

    PubMed

    Walfield, Scott M

    2016-05-01

    As rape remains one of the most underreported and least likely to be cleared of the violent crimes, it is of paramount importance to understand the factors associated with the likelihood of a case being cleared by law enforcement. This study uses data from the National Incident-Based Reporting System (NIBRS) and the Law Enforcement Management and Administrative Statistics (LEMAS), and a multilevel modeling approach to examine the relationship between victim, offender, incident, and police department characteristics contrasting the two types of clearance: arrest and exceptional clearance. The latter occurs due to reasons outside of law enforcement's control and despite being considered cleared, the offender is not arrested, charged, nor turned over for prosecution. Of the 16,231 cleared rapes in 238 departments, nearly half (47%) results in exceptional clearance when the victim refuses to cooperate or when prosecution is declined. Incident-level variables have a greater effect on the likelihood of exceptional clearance than victim and offender variables. The department explained a nontrivial amount of variation in the dependent variable, as 37% of the variance in type of clearance was between-department variation. Implications for future research on exceptional clearance and NIBRS are discussed.

  10. LETTER: Toroidally asymmetric ELM precursors in TCV

    NASA Astrophysics Data System (ADS)

    Reimerdes, H.; Pochelon, A.; Suttrop, W.

    1998-03-01

    Coherent magnetic oscillations precede edge localized modes (ELMs) in TCV. The precursor has been detected prior to ELMs considered to be of type III and others previously referred to as TCV large ELMs. This permits the identification of both as type III ELMs according to the usual classification scheme. The strong localization of these precursors on the bad curvature side of the plasma and their medium toroidal mode numbers indicate their ballooning character. Unlike conventional MHD modes, these modes start toroidally localized and grow in amplitude and toroidal extent. When the precursor encompasses the whole toroidal circumference, the increased transport phase, as indicated by the characteristic Dα spike, begins.

  11. Synthesis and structures of metal chalcogenide precursors

    NASA Technical Reports Server (NTRS)

    Hepp, Aloysius F.; Duraj, Stan A.; Eckles, William E.; Andras, Maria T.

    1990-01-01

    The reactivity of early transition metal sandwich complexes with sulfur-rich molecules such as dithiocarboxylic acids was studied. Researchers recently initiated work on precursors to CuInSe2 and related chalcopyrite semiconductors. Th every high radiation tolerance and the high absorption coefficient of CuInSe2 makes this material extremely attractive for lightweight space solar cells. Their general approach in early transition metal chemistry, the reaction of low-valent metal complexes or metal powders with sulfur and selenium rich compounds, was extended to the synthesis of chalcopyrite precursors. Here, the researchers describe synthesis, structures, and and routes to single molecule precursors to metal chalcogenides.

  12. 17 CFR 22.16 - Disclosures to Cleared Swaps Customers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) of this section, relating to use of Cleared Swaps Customer Collateral, transfer, neutralization of... use of Cleared Swaps Customer Collateral, transfer, neutralization of the risks, or liquidation...

  13. 17 CFR 22.16 - Disclosures to Cleared Swaps Customers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) of this section, relating to use of Cleared Swaps Customer Collateral, transfer, neutralization of... use of Cleared Swaps Customer Collateral, transfer, neutralization of the risks, or liquidation...

  14. Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation

    PubMed Central

    Jäkel, Sarah; Dimou, Leda

    2017-01-01

    Glial cells, consisting of microglia, astrocytes, and oligodendrocyte lineage cells as their major components, constitute a large fraction of the mammalian brain. Originally considered as purely non-functional glue for neurons, decades of research have highlighted the importance as well as further functions of glial cells. Although many aspects of these cells are well characterized nowadays, the functions of the different glial populations in the brain under both physiological and pathological conditions remain, at least to a certain extent, unresolved. To tackle these important questions, a broad range of depletion approaches have been developed in which microglia, astrocytes, or oligodendrocyte lineage cells (i.e., NG2-glia and oligodendrocytes) are specifically ablated from the adult brain network with a subsequent analysis of the consequences. As the different glial populations are very heterogeneous, it is imperative to specifically ablate single cell populations instead of inducing cell death in all glial cells in general. Thanks to modern genetic manipulation methods, the approaches can now directly be targeted to the cell type of interest making the ablation more specific compared to general cell ablation approaches that have been used earlier on. In this review, we will give a detailed summary on different glial ablation studies, focusing on the adult mouse central nervous system and the functional readouts. We will also provide an outlook on how these approaches could be further exploited in the future. PMID:28243193

  15. Oligodendrocyte Precursor Cells Synthesize Neuromodulatory Factors

    PubMed Central

    Sakry, Dominik; Yigit, Hatice; Dimou, Leda; Trotter, Jacqueline

    2015-01-01

    NG2 protein-expressing oligodendrocyte progenitor cells (OPC) are a persisting and major glial cell population in the adult mammalian brain. Direct synaptic innervation of OPC by neurons throughout the brain together with their ability to sense neuronal network activity raises the question of additional physiological roles of OPC, supplementary to generating myelinating oligodendrocytes. In this study we investigated whether OPC express neuromodulatory factors, typically synthesized by other CNS cell types. Our results show that OPC express two well-characterized neuromodulatory proteins: Prostaglandin D2 synthase (PTGDS) and neuronal Pentraxin 2 (Nptx2/Narp). Expression levels of the enzyme PTGDS are influenced in cultured OPC by the NG2 intracellular region which can be released by cleavage and localizes to glial nuclei upon transfection. Furthermore PTGDS mRNA levels are reduced in OPC from NG2-KO mouse brain compared to WT cells after isolation by cell sorting and direct analysis. These results show that OPC can contribute to the expression of these proteins within the CNS and suggest PTGDS expression as a downstream target of NG2 signaling. PMID:25966014

  16. Progress in molecular precursors for electronic materials

    SciTech Connect

    Buhro, W.E.

    1996-09-01

    Molecular-precursor chemistry provides an essential underpinning to all electronic-materials technologies, including photovoltaics and related areas of direct interest to the DOE. Materials synthesis and processing is a rapidly developing field in which advances in molecular precursors are playing a major role. This article surveys selected recent research examples that define the exciting current directions in molecular-precursor science. These directions include growth of increasingly complex structures and stoichiometries, surface-selective growth, kinetic growth of metastable materials, growth of size-controlled quantum dots and quantum-dot arrays, and growth at progressively lower temperatures. Continued progress in molecular-precursor chemistry will afford precise control over the crystal structures, nanostructures, and microstructures of electronic materials.

  17. Biochemical Removal of HAP Precursors From Coal

    SciTech Connect

    Olson, G.; Tucker, L.; Richards, J.

    1997-07-01

    This project addresses DOE`s interest in advanced concepts for controlling emissions of air toxics from coal-fired utility boilers. We are determining the feasibility of developing a biochemical process for the precombustion removal of substantial percentages of 13 inorganic hazardous air pollutant (HAP) precursors from coal. These HAP precursors are Sb, As, Be, Cd, Cr, Cl, Co, F, Pb, Hg, Mn, Ni, and Se. Although rapid physical coal cleaning is done routinely in preparation plants, biochemical processes for removal of HAP precursors from coal potentially offer advantages of deeper cleaning, more specificity, and less coal loss. Compared to chemical processes for coal cleaning, biochemical processes potentially offer lower costs and milder process conditions. Pyrite oxidizing bacteria, most notably Thiobacillusferrooxidans, are being evaluated in this project for their ability to remove HAP precursors from U.S. coals.

  18. Explorations Precursor Robotic Missions (xPRM)

    NASA Video Gallery

    Jay Jenkins delivers a presentation from the Exploration Precursor Robotic Missions (xPRM) study team on May 25, 2010, at the NASA Exploration Enterprise Workshop held in Galveston, TX. The purpose...

  19. Clear New View of a Classic Spiral

    NASA Astrophysics Data System (ADS)

    2010-05-01

    ESO is releasing a beautiful image of the nearby galaxy Messier 83 taken by the HAWK-I instrument on ESO's Very Large Telescope (VLT) at the Paranal Observatory in Chile. The picture shows the galaxy in infrared light and demonstrates the impressive power of the camera to create one of the sharpest and most detailed pictures of Messier 83 ever taken from the ground. The galaxy Messier 83 (eso0825) is located about 15 million light-years away in the constellation of Hydra (the Sea Serpent). It spans over 40 000 light-years, only 40 percent the size of the Milky Way, but in many ways is quite similar to our home galaxy, both in its spiral shape and the presence of a bar of stars across its centre. Messier 83 is famous among astronomers for its many supernovae: vast explosions that end the lives of some stars. Over the last century, six supernovae have been observed in Messier 83 - a record number that is matched by only one other galaxy. Even without supernovae, Messier 83 is one of the brightest nearby galaxies, visible using just binoculars. Messier 83 has been observed in the infrared part of the spectrum using HAWK-I [1], a powerful camera on ESO's Very Large Telescope (VLT). When viewed in infrared light most of the obscuring dust that hides much of Messier 83 becomes transparent. The brightly lit gas around hot young stars in the spiral arms is also less prominent in infrared pictures. As a result much more of the structure of the galaxy and the vast hordes of its constituent stars can be seen. This clear view is important for astronomers looking for clusters of young stars, especially those hidden in dusty regions of the galaxy. Studying such star clusters was one of the main scientific goals of these observations [2]. When compared to earlier images, the acute vision of HAWK-I reveals far more stars within the galaxy. The combination of the huge mirror of the VLT, the large field of view and great sensitivity of the camera, and the superb observing conditions

  20. Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production.

    PubMed

    Hisaoka, Kazue; Tsuchioka, Mami; Yano, Ryoya; Maeda, Natsuko; Kajitani, Naoto; Morioka, Norimitsu; Nakata, Yoshihiro; Takebayashi, Minoru

    2011-06-17

    Recently, both clinical and animal studies demonstrated neuronal and glial plasticity to be important for the therapeutic action of antidepressants. Antidepressants increase glial cell line-derived neurotrophic factor (GDNF) production through monoamine-independent protein-tyrosine kinase, extracellular signal-regulated kinase (ERK), and cAMP responsive element-binding protein (CREB) activation in glial cells (Hisaoka, K., Takebayashi, M., Tsuchioka, M., Maeda, N., Nakata, Y., and Yamawaki, S. (2007) J. Pharmacol. Exp. Ther. 321, 148-157; Hisaoka, K., Maeda, N., Tsuchioka, M., and Takebayashi, M. (2008) Brain Res. 1196, 53-58). This study clarifies the type of tyrosine kinase and mechanism of antidepressant-induced GDNF production in C6 glioma cells and normal human astrocytes. The amitriptyline (a tricyclic antidepressant)-induced ERK activation was specifically and completely inhibited by fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors and siRNA for FGFR1 and -2. Treatment with amitriptyline or several different classes of antidepressants, but not non-antidepressants, acutely increased the phosphorylation of FGFRs and FGFR substrate 2α (FRS2α). Amitriptyline-induced CREB phosphorylation and GDNF production were blocked by FGFR-tyrosine kinase inhibitors. Therefore, antidepressants activate the FGFR/FRS2α/ERK/CREB signaling cascade, thus resulting in GDNF production. Furthermore, we attempted to elucidate how antidepressants activate FGFR signaling. The effect of amitriptyline was inhibited by heparin, non-permeant FGF-2 neutralizing antibodies, and matrix metalloproteinase (MMP) inhibitors. Serotonin (5-HT) also increased GDNF production through FGFR2 (Tsuchioka, M., Takebayashi, M., Hisaoka, K., Maeda, N., and Nakata, Y. (2008) J. Neurochem. 106, 244-257); however, the effect of 5-HT was not inhibited by heparin and MMP inhibitors. These results suggest that amitriptyline-induced FGFR activation might occur through an extracellular pathway

  1. Hydridosiloxanes as precursors to ceramic products

    DOEpatents

    Blum, Y.D.; Johnson, S.M.; Gusman, M.I.

    1997-06-03

    A method is provided for preparing ceramic precursors from hydridosiloxane starting materials and then pyrolyzing these precursors to give rise to silicious ceramic materials. Si-H bonds present in the hydridosiloxane starting materials are catalytically activated, and the activated hydrogen atoms may then be replaced with nonhydrogen substituents. These preceramic materials are pyrolyzed in a selected atmosphere to give the desired ceramic product. Ceramic products which may be prepared by this technique include silica, silicon oxynitride, silicon carbide, metal silicates, and mullite.

  2. Compliance Testing of the Clear AFS Power Plant, Coal-Fired Boiler 1 Clear AFS, Alaska

    DTIC Science & Technology

    1989-10-01

    Background On 3 February 1987 Clear AFS requested a permit modification to allow limited burning of waste oil for their power plant shown in Figure 1...The Alaska DEC rescindel Permit to Operate No. 8331-AA003 and issued Permit No. 8731-AA004 (Appendix B) allowing the burning of waste oil. As a...below. 1. Visible Emissions (18 AAC 50.050(a)) Visible emissions, excluding condensed water vapor from an industrial process or fuel burning

  3. Data-driven model comparing the effects of glial scarring and interface interactions on chronic neural recordings in non-human primates

    NASA Astrophysics Data System (ADS)

    Malaga, Karlo A.; Schroeder, Karen E.; Patel, Paras R.; Irwin, Zachary T.; Thompson, David E.; Bentley, J. Nicole; Lempka, Scott F.; Chestek, Cynthia A.; Patil, Parag G.

    2016-02-01

    Objective. We characterized electrode stability over twelve weeks of impedance and neural recording data from four chronically-implanted Utah arrays in two rhesus macaques, and investigated the effects of glial scarring and interface interactions at the electrode recording site on signal quality using a computational model. Approach. A finite-element model of a Utah array microelectrode in neural tissue was coupled with a multi-compartmental model of a neuron to quantify the effects of encapsulation thickness, encapsulation resistivity, and interface resistivity on electrode impedance and waveform amplitude. The coupled model was then reconciled with the in vivo data. Histology was obtained seventeen weeks post-implantation to measure gliosis. Main results. From week 1-3, mean impedance and amplitude increased at rates of 115.8 kΩ/week and 23.1 μV/week, respectively. This initial ramp up in impedance and amplitude was observed across all arrays, and is consistent with biofouling (increasing interface resistivity) and edema clearing (increasing tissue resistivity), respectively, in the model. Beyond week 3, the trends leveled out. Histology showed that thin scars formed around the electrodes. In the model, scarring could not match the in vivo data. However, a thin interface layer at the electrode tip could. Despite having a large effect on impedance, interface resistivity did not have a noticeable effect on amplitude. Significance. This study suggests that scarring does not cause an electrical problem with regard to signal quality since it does not appear to be the main contributor to increasing impedance or significantly affect amplitude unless it displaces neurons. This, in turn, suggests that neural signals can be obtained reliably despite scarring as long as the recording site has sufficiently low impedance after accumulating a thin layer of biofouling. Therefore, advancements in microelectrode technology may be expedited by focusing on improvements to the

  4. Decrease of glial cell-derived neurotrophic factor contributes to anesthesia- and surgery-induced learning and memory dysfunction in neonatal rats.

    PubMed

    Gui, Lingli; Lei, Xi; Zuo, Zhiyi

    2017-04-01

    Long duration of anesthesia may induce toxicity in the developing brain. However, little is known about the effects of the combination of surgery and anesthesia on the developing brain. The mechanisms for the effects are not clear. To determine these effects, postnatal day 7 male and female Sprague-Dawley rats were exposed to 3% sevoflurane for 2 h with or without right common carotid exposure. Pyrrolidine dithiocarbamate (PDTC), an anti-inflammatory agent, was given 30 min before and 6 h after the carotid exposure. Anti-glial cell-derived neurotrophic factor (GDNF) antibody or GDNF was given at the end of sevoflurane exposure. We found that anesthesia-surgery induced learning and memory impairment assessed by Barnes maze and fear conditioning. Anesthesia-surgery also induced neuroinflammation and reduced the level of glial cell-derived neurotrophic factor (GDNF, 10.6 ± 0.6 pg/mg protein of control rats vs. 7.7 ± 0.4 pg/mg protein of anesthesia-surgery rats, n = 17, p = 0.007) and neurogenesis in the hippocampus. PDTC inhibited these surgical effects (GDNF level 9.7 ± 0.6 pg/mg protein of anesthesia-surgery plus PDTC rats, n = 17, p = 0.763 vs. control rats). Intracerebroventricular injection of an anti-GDNF antibody but not its heat-inactivated form induced learning and memory impairment in control rats. Intracerebroventricular injection of GDNF attenuated learning and memory impairment after anesthesia-surgery. We conclude that anesthesia-surgery in neonatal rats induces neuroinflammation, which then leads to a decreased level of GDNF and neurogenesis in the hippocampus and cognitive impairment. GDNF decrease plays an important role in anesthesia-surgery-induced cognitive impairment.

  5. Ontogenesis of the reticulum with special reference to neuroendocrine and glial cells: a comparative analysis of the Merino sheep and Iberian red deer.

    PubMed

    Franco, A; Masot, J; García, A; Redondo, E

    2012-10-01

    The present study was designed to compare the differences in the ontogenesis of the reticulum in sheep (domestic ruminant) and deer (wild ruminant). A total of 50 embryos and foetuses Merino sheep and 50 Iberian deer were used, from the first pre-natal life until birth. The appearance of the reticulum from the primitive gastric tube was earlier in the sheep (22% gestation, 33 days) than in the deer (25% gestation, 66 days). In both cases, it displayed a primitive epithelium of a stratified, cylindrical, non-ciliary type. At around 48% gestation in the sheep (72 days) and 36% (97 days) in the deer, the reticulum was configured of four clearly differentiated layers: mucosa (with epithelial layer and lamina propria), submucosa, tunica muscularis and serosa. The stratification of the epithelial layer was accompanied by modifications in its structure with the appearance of the primitive reticular ribs. The primary ribs began to be formed first in the deer, at 117 days of pre-natal life (40% gestation) and later in the sheep (79 days, 53% gestation). The differentiation of the corneum papillae in the primary ribs coincided with the appearance of secondary reticular ribs. These structures began to be formed first in the deer, at 142 days of pre-natal life (51% gestation) and later in the sheep (83 days, 55% gestation). The presence of neuroendocrine cells (non-neuronal enolase-positive cells) in the reticular mucosa was not detected until 97 days (36% gestation) in deer and 81 days (54% gestation) in sheep. The presence of glial cells (GFAP-positive cells) occurred at around 142 days (51% gestation) in deer and at 112 days (75% gestation) in sheep. In conclusion, the presence of neuroendocrine and glial cells was detected in deer at earlier stages than sheep.

  6. Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development.

    PubMed

    Viktorin, Gudrun; Riebli, Nadia; Popkova, Anna; Giangrande, Angela; Reichert, Heinrich

    2011-08-15

    The neural stem cells that give rise to the neural lineages of the brain can generate their progeny directly or through transit amplifying intermediate neural progenitor cells (INPs). The INP-producing neural stem cells in Drosophila are called type II neuroblasts, and their neural progeny innervate the central complex, a prominent integrative brain center. Here we use genetic lineage tracing and clonal analysis to show that the INPs of these type II neuroblast lineages give rise to glial cells as well as neurons during postembryonic brain development. Our data indicate that two main types of INP lineages are generated, namely mixed neuronal/glial lineages and neuronal lineages. Genetic loss-of-function and gain-of-function experiments show that the gcm gene is necessary and sufficient for gliogenesis in these lineages. The INP-derived glial cells, like the INP-derived neuronal cells, make major contributions to the central complex. In postembryonic development, these INP-derived glial cells surround the entire developing central complex neuropile, and once the major compartments of the central complex are formed, they also delimit each of these compartments. During this process, the number of these glial cells in the central complex is increased markedly through local proliferation based on glial cell mitosis. Taken together, these findings uncover a novel and complex form of neurogliogenesis in Drosophila involving transit amplifying intermediate progenitors. Moreover, they indicate that type II neuroblasts are remarkably multipotent neural stem cells that can generate both the neuronal and the glial progeny that make major contributions to one and the same complex brain structure.

  7. Growth and differentiation factor 10 (Gdf10) is involved in Bergmann glial cell development under Shh regulation.

    PubMed

    Mecklenburg, Nora; Martinez-Lopez, Jesus E; Moreno-Bravo, Juan Antonio; Perez-Balaguer, Ariadna; Puelles, Eduardo; Martinez, Salvador

    2014-10-01

    Growth differentiation factor 10 (Gdf10), also known as Bmp3b, is a member of the transforming growth factor (TGF)-ß superfamily. Gdf10 is expressed in Bergmann glial cells, which was investigated by single-cell transcriptional profiling (Koirala and Corfas, (2010) PLoS ONE 5: e9198). Here we provide a detailed characterization of Gdf10 expression from E14, the stage at which Gdf10 is expressed for the first time in the cerebellum, until P28. We detected Gdf10 expression in both germinal zones: in the ventricular zone (VZ) of the 4th ventricle as well as in the rhombic lip (RL). The VZ has been postulated to give rise to GABAergic neurons and glial cells, whereas the RL gives rise to glutamatergic neurons. Thus, it was very surprising to discover a gene that is expressed exclusively in glial cells and is not restricted to an expression in the VZ, but is also present in the RL. At postnatal stages Gdf10 was distributed equally in Bergmann glial cells of the cerebellum. Furthermore, we found Gdf10 to be regulated by Sonic hedgehog (Shh), which is secreted by Purkinje cells of the cerebellum. In the conditional Shh mutants, glial cells showed a reduced expression of Gdf10, whereas the expression of Nestin and Vimentin was unchanged. Thus, we show for the first time, that Gdf10, expressed in Bergmann glial cells, is affected by the loss of Shh as early as E18.5, suggesting a regulation of glial development by Shh.

  8. High-fat diet and age-dependent effects on enteric glial cell populations of mouse small intestine.

    PubMed

    Stenkamp-Strahm, Chloe; Patterson, Savannah; Boren, Jennifer; Gericke, Martin; Balemba, Onesmo

    2013-10-01

    Diabetes and obesity are increasing in prevalence at an alarming rate throughout the world. Autonomic diabetic neuropathy is evident in individuals that experience a long-standing diabetic disease state, and gastrointestinal (GI) dysmotility is thought to be the outcome of neuropathies within the enteric nervous system (ENS) of these patients. To date, an analysis of enteric glial cell population changes during diabetic symptoms has not been performed, and may bring insight into disease pathology and neuropathy, given glial cell implications in gastrointestinal and neuronal homeostasis. Diabetes and obesity were monitored in C57Bl/6J mice fed a 72% high-fat diet, and duodenal glial expression patterns were evaluated by immunohistochemistry and RT-PCR for S100β, Sox10 and GFAP proteins and transcripts, as well as transmission electron microscopy (TEM). The high-fat diet caused obesity, hyperglycemia and insulin resistance after 4 weeks. These changes were associated with a significant decline in the area density indices of mucosa-associated glial cell networks, evidenced by S100β staining at 8 and 20 weeks. All three markers and TEM showed that myenteric glial cells were unaffected by early and late disease periods. However, analysis of Sox10 transcript expression and immunoreactivity showed a diet independent, age-associated decline in glial cell populations. This is the first study showing that mucosal glia cell damage occurs during diabetic symptoms, suggesting that mucosal enteric glia injury may have a pathophysiological significance during this disease. Our results also provide support for age-associated changes in longitudinal studies of enteric glial cells.

  9. 17 CFR 39.8 - Fraud in connection with the clearing of transactions on a derivatives clearing organization.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Fraud in connection with the clearing of transactions on a derivatives clearing organization. 39.8 Section 39.8 Commodity and Securities... Applicable to Derivatives Clearing Organizations § 39.8 Fraud in connection with the clearing of...

  10. 17 CFR 39.8 - Fraud in connection with the clearing of transactions on a derivatives clearing organization.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Fraud in connection with the clearing of transactions on a derivatives clearing organization. 39.8 Section 39.8 Commodity and Securities... Applicable to Derivatives Clearing Organizations § 39.8 Fraud in connection with the clearing of...

  11. Resonant infrared pulsed laser deposition of a polyimide precursor

    NASA Astrophysics Data System (ADS)

    Dygert, N. L.; Schriver, K. E.; Haglund, R. F., Jr.

    2007-04-01

    Poly(amic acid) (PAA), a precursor to polyimide, was successfully deposited on substrates without reaching curing temperature, by resonant infrared pulsed laser ablation. The PAA was prepared by dissolving pyromellitic dianhydride and 4, 4' oxidianiline in the polar solvent Nmethyl pyrrolidinone (NMP). The PAA was deposited in droplet-like morphologies when ablation occurred in air, and in string-like moieties in the case of ablation in vacuum. In the as-deposited condition, the PAA was easily removed by washing with NMP; however, once cured thermally for thirty minutes, the PAA hardened, indicating the expected thermosetting property. Plume shadowgraphy showed very clear contrasts in the ablation mechanism between ablation of the solvent alone and the ablation of the PAA, even at low concentrations. A Wavelength dependence in plume velocity was also observed.

  12. Tilt precursors before earthquakes on the San Andreas fault, California

    USGS Publications Warehouse

    Johnston, M.J.S.; Mortensen, C.E.

    1974-01-01

    An array of 14 biaxial shallow-borehole tiltmeters (at 10-7 radian sensitivity) has been installed along 85 kilometers of the San Andreas fault during the past year. Earthquake-related changes in tilt have been simultaneously observed on up to four independent instruments. At earthquake distances greater than 10 earthquake source dimensions, there are few clear indications of tilt change. For the four instruments with the longest records (>10 months), 26 earthquakes have occurred since July 1973 with at least one instrument closer than 10 source dimensions and 8 earthquakes with more than one instrument within that distance. Precursors in tilt direction have been observed before more than 10 earthquakes or groups of earthquakes, and no similar effect has yet been seen without the occurrence of an earthquake.

  13. Magnolol protects against trimethyltin-induced neuronal damage and glial activation in vitro and in vivo.

    PubMed

    Kim, Da Jung; Kim, Yong Sik

    2016-03-01

    Trimethyltin (TMT), an organotin with potent neurotoxic effects by selectively damaging to hippocampus, is used as a tool for creating an experimental model of neurodegeneration. In the present study, we investigated the protective effects of magnolol, a natural biphenolic compound, on TMT-induced neurodegeneration and glial activation in vitro and in vivo. In HT22 murine neuroblastoma cells, TMT induced necrotic/apoptotic cell death and oxidative stress, including intracellular reactive oxygen species (ROS), protein carbonylation, induction of heme oxygenase-1 (HO-1), and activation of all mitogen-activated protein kinases (MAPKs) family proteins. However, magnolol treatment significantly suppressed neuronal cell death by inhibiting TMT-mediated ROS generation and activation of JNK and p38 MAPKs. In BV-2 microglial cells, magnolol efficiently attenuated TMT-induced microglial activation via suppression of ROS generation and activation of JNK, p38 MAPKs, and nuclear factor-κB (NF-κB) signaling. In an in vivo mouse study, TMT induced massive neuronal damage and enhanced oxidative stress at day 2. We also observed a concomitant increase in glial cells and inducible nitric oxide synthase (iNOS) expression on the same day. These features of TMT toxicity were reversed by treatment of magnolol. We observed that p-JNK and p-p38 MAPK levels were increased in the mouse hippocampus at day 1 after TMT treatment and that magnolol blocked TMT-induced JNK and p38 MAPK activation. Magnolol administration prevented TMT-induced hippocampal neurodegeneration and glial activation, possibly through the regulation of TMT-mediated ROS generation and MAPK activation.

  14. Glial Cells - The Key Elements of Alzheimer´s Disease.

    PubMed

    Dzamba, David; Harantova, Lenka; Butenko, Olena; Anderova, Miroslava

    2016-01-01

    Alzheimer's disease (AD) is a complex neurodegenerative disorder with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Besides the extensive neuron-oriented research, an increasing body of evidence suggests that glial cells, namely astrocytes, microglia, NG2 glia and oligodendrocytes, may play an important role in the pathogenesis of this disease. In the first part of this review, AD pathophysiology in humans is briefly described and compared with disease progression in routinely used animal models. The relevance of findings obtained in animal models of AD is also discussed with respect to AD pathology in humans. Further, this review summarizes recent findings regarding the role/participation of glial cells in pathogenesis of AD, focusing on changes in their morphology, functions, proteins and gene expression profiles. As for astrocytes and microglia, they are fundamental for the progression and outcome of AD either because they function as effector cells releasing cytokines that play a role in neuroprotection, or because they fail to fulfill their homeostatic functions, ultimately leaving neurons to face excitotoxicity and oxidative stress. Next, we turn our attention towards NG2 glia, a novel and distinct class of glial cells in the central nervous system (CNS), whose role in a variety of human CNS diseases has begun to emerge, and we also consider the participation of oligodendrocytes in the pathogenesis and progression of AD. Since AD is currently an incurable disease, in the last part of our review we hypothesize about possible glia-oriented treatments and provide a perspective of possible future advancements in this field.

  15. Glial reaction to photoelectric dye-based retinal prostheses implanted in the subretinal space of rats.

    PubMed

    Tamaki, Takayuki; Matsuo, Toshihiko; Hosoya, Osamu; Tsutsui, Kimiko M; Uchida, Tetsuya; Okamoto, Kazuo; Uji, Akihito; Ohtsuki, Hiroshi

    2008-01-01

    We have designed a new type of retinal prosthesis using polyethylene films coupled with photoelectric dye molecules that absorb light and convert photon energy to electric potentials. An extruded-blown film of high-density polyethylene was used as the original polyethylene film. Recrystallized film was made by recrystallization from the melting of the original polyethylene film. A photoelectric dye,2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to the two types of polyethylene films through amide linkages. Samples of the original dye-coupled film, the dye-coupled recrystallized film, and the dye-uncoupled plain film were implanted in the subretinal space of normal adult rats. Frozen sections were cut from the eyes enucleated at 1 week or 1 month and were either stained with hematoxylin and eosin, stained immunohistochemically for glial fibrillary acidic protein (GFAP), or processed for in situ apoptosis detection. The results revealed that retinal tissue damage was negligible with no inflammatory cells and few apoptotic cells. GFAP was significantly up-regulated in retinal sites with the implantation of all types of polyethylene films at 1 week, compared with the adjacent retinal sites (P < 0.005, analysis of variance). The GFAP up-regulation was also present at 1 month for the plain film and dye-coupled recrystallized film (P < 0.05). Glial cell encirclement around the films increased significantly between 1 week and 1 month (P = 0.023, two-factor analysis of variance) but was not significantly different among the three types of polyethylene films (P = 0.4531). These results showed evidence of glial reactions to the photoelectric dye-coupled polyethylene films implanted into the subretinal space of rat eyes and also proved their basic biological safety.

  16. Glial reactions to argon laser photocoagulation injury in rabbit and rat retinas

    NASA Astrophysics Data System (ADS)

    Humphrey, Martin F.; Chu, Yi; Sharp, Claudia; Moore, Stephen; Mann, Krishna; Rakoczy, Piroska; Constable, Ian J.

    1996-04-01

    Argon laser photocoagulation is a standard and effective clinical technique for a variety of disease conditions. However there is evidence that coagulation produces more widespread alterations in the retina than the local scarring at the injury site. For example, in diabetic retinopathy multiple photocoagulations in the retinal periphery can control blood vessel growth in the central retina. Therefore we have studied the changes in retinal glial cells following photocoagulation using immunocytochemical techniques with an emphasis on the spread of cellular reactions by using whole, flatmounted retinal preparations. Muller glial cells do not normally express the cytoskeletal protein GFAP (glial fibrillary acidic protein) but do so after a variety of injuries. We found that there is a very widespread expression of GFAP by Muller cells even after very focal coagulations and that this persists for 1 - 1.5 months after coagulation. The microglial cells are primed to react to injury and can release very powerful effector molecules and we therefore also examined the microglial reaction to see whether it correlated with the Muller cell reaction. However, we found that the microglial response, in terms of anatomical changes, was very focally confined to regions of direct cellular injury. We also examined MHC II expression to see whether microglia expressed this activity related protein without anatomical changes but we found no evidence of wide spread changes. In summary we find that inflammatory reactions are very localized after coagulation but the macroglial changes are more widespread and therefore the distant effects of photocoagulation may be more related to macroglial reactions.

  17. Mechanisms of a Glial Modulating Agent, Propentofylline: Potential New Treatment for Glioblastoma Multiforme

    NASA Astrophysics Data System (ADS)

    Jacobs, Valerie

    Glioblastoma multiforme is the most common and aggressive primary brain tumor with a very poor prognosis despite multi-modalities of treatment. As a result, there is a critical need to develop alternative therapies. Propentofylline (PPF) is a methyl xanthine with glial modulating properties. Based on known mechanisms of PPF and the important role of glial cells in glioma growth, we hypothesized that PPF can target glial cells in the tumor microenvironment, decreasing tumor growth. More specifically, PPF can target microglia and astrocytes. In Chapter 3 we demonstrate that PPF decreases microglia migration towards CNS-1 cells, decreases CNS-1 cells invasion when cultured with microglia and decreases MMP-9 expression in microglia. In Chapter 4 we showed that PPF decreases TROY expression in microglia. In Chapter 5 we showed PPF causes astrocytes to increase glutamate uptake through the GLT-1 transporter, leading to less glutamate available for CNS-1 cells, ultimately resulting in increased CNS-1 cell apoptosis. Finally, in Chapter 6 we present supportive data that PPF uniquely targets resident microglia in the CNS due to pharmacological differences between species and cell types. This thesis describes the following major contributions to the field of glioma research: 1) identification of propentofylline as a possible new drug for GBM treatment that targets microglia and astrocytes, decreasing brain tumor growth in vivo, and further supporting a different functional role of microglia and infiltrating macrophages in the tumor microenvironment, 2) identification of TROY as a novel signaling molecule expressed in microglia in response to CNS-1 cells and involved in microglia migration, and 3) identification of differential responses between species and cell types with propentofylline treatment.

  18. Prenatal diagnosis and genetic discoveries of an intracranial mixed neuronal-glial tumor

    PubMed Central

    Sun, Lijuan; Wu, Qingqing; Pei, Yan; Li, Jinghua; Ye, Jintang; Zhi, Wenxue; Liu, Yan; Zhang, Puqing

    2016-01-01

    Abstract Background: Congenital intracranial tumors as a group are quite rare, representing only 0.5% to 1.5% of all pediatric brain neoplasms. Case report: We reported a case of congenital mixed neuronal-glial tumor detected by ultrasound at 30 weeks of gestation. It showed that the tumor was 2.5 × 2.3 × 2.1 cm3 in size, located in the sellar region, regular shape, and slightly heterogeneous solid mass with a little cystic component. No color flow was present inside the tumor, but the peripheral encirclement by arterial circle of Willis. No other associated malformations were detected. Prenatal magnetic resonance imaging (MRI) which was taken subsequently confirmed the result of ultrasound and provided more detailed information such as fetal brain dysplasia. The fetal chromosomal karyotype analysis is normal. Single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) detected a 0.72-Mb duplication at 4q35.2 in fetus which was associated with epilepsy and cardiac anomalies. It also revealed a 0.13-Mb deletion at 6q26 located in PARK2 gene, and the mutation of the gene is known to be related to autosomal recessive juvenile Parkinson disease. The parents chose termination of pregnancy (TOP). The histological examination showed a mixed neuronal-glial tumor. Conclusion: Prenatal detection of mixed neuronal-glial tumor is very rare. Ultrasound is of critical importance to detect the intracranial tumors, and MRI can give us some detailed information about the tumors. However, the precise histologic type was depended on the pathological examination. CMA should be necessary for the fetuses with congenital intracranial tumors, especially when the fetal chromosomal karyotype analysis is normal. PMID:27828868

  19. Surgical Resection of Non-Glial Tumors in the Motor Cortex

    PubMed Central

    Lee, Seong-Jong; Im, Soo Bin; Kim, Bum-Tae

    2016-01-01

    Background Direct surgery to resect tumors in the motor cortex could improve neurological symptoms or cause novel motor weakness. The present study describes the neurological outcomes of patients after the surgical resection of non-glial tumors in the primary motor cortex. Methods The present study included 25 patients who had pathologically confirmed non-glial tumors in the motor cortex for which they underwent surgery. Tumor location was verified using anatomical landmarks on preoperative magnetic resonance imaging scans. All surgeries involved a craniotomy and tumor resection, especially use of the sulcal dissecting approach for intra-axial tumors. Results Of the 25 patients, 10 exhibited metastasis, 13 had a meningioma, and 2 had a cavernous malformation. Motor weakness and seizures were the most common symptoms, while 3 patients experienced only a headache. The tumor size was less than 20 mm in 4 patients, 20–40 mm in 14, and greater than 40 mm in seven. Of the 25 patients, 13 exhibited motor weakness prior to the operation, but most of these symptoms (76.9%) improved following surgery. On the other hand, eight patients experienced seizures prior to the surgery, and in three of these patients (37.5%), the seizures were not controlled after the surgery. In terms of surgical complications, a postoperative hematoma developed in one of the meningioma patients, and the patient's hemiparesis was aggravated. Conclusion The present findings show that careful and meticulous resection of non-glial tumors in the motor cortex can improve preoperative neurological signs, but it cannot completely control seizure activity. PMID:27867915

  20. Cytoprotective and anti-inflammatory effects of PAL31 overexpression in glial cells

    PubMed Central

    2014-01-01

    Background Acute spinal cord injury (SCI) leads to a series of reactive changes and causes severe neurological deficits. A pronounced inflammation contributes to secondary pathology after SCI. Astroglia respond to SCI by proliferating, migrating, and altering phenotype. The impact of reactive gliosis on the pathogenesis of SCI is not fully understood. Our previous study has identified an inflammatory modulating protein, proliferation related acidic leucine-rich protein (PAL31) which is upregulated in the microglia/macrophage of injured cords. Because PAL31 participates in cell cycle progression and reactive astroglia often appears in the injured cord, we aim to examine whether PAL31 is involved in glial modulation after injury. Results Enhanced PAL31 expression was shown not only in microglia/macrophages but also in spinal astroglia after SCI. Cell culture study reveal that overexpression of PAL31 in mixed glial cells or in C6 astroglia significantly reduced LPS/IFNγ stimulation. Further, enhanced PAL31 expression in C6 astroglia protected cells from H2O2 toxicity; however, this did not affect its proliferative activity. The inhibiting effect of PAL31 on LPS/IFNγ stimulation was observed in glia or C6 after co-culture with neuronal cells. The results demonstrated that the overexpressed PAL31 in glial cells protected neuronal damages through inhibiting NF-kB signaling and iNOS. Conclusions Our data suggest that PAL31upregulation might be beneficial after spinal cord injury. Reactive gliosis might become a good target for future therapeutic interventions. PMID:25034417

  1. Characterisation of neuronal and glial populations of the visual system during zebrafish lifespan.

    PubMed

    Arenzana, F J; Santos-Ledo, A; Porteros, A; Aijón, J; Velasco, A; Lara, J M; Arévalo, R

    2011-06-01

    During visual system morphogenesis, several cell populations arise at different time points correlating with the expression of specific molecular markers We have analysed the distribution pattern of three molecular markers (zn-1, calretinin and glial fibrillary acidic protein) which are involved in the development of zebrafish retina and optic tectum. zn-1 is a neural antigen expressed in the developing zebrafish central nervous system. Calretinin is the first calcium-binding protein expressed in the central nervous system of vertebrates and it is widely distributed in different neuronal populations of vertebrate retina, being a valuable marker for its early and late development. Glial fibrillary acidic protein (GFAP), which is an astroglial marker, is a useful tool for characterising the glial environment in which the optic axons develop. We describe the expression profile changes in these three markers throughout the zebrafish lifespan with special attention to ganglion cells and their projections. zn-1 is expressed in the first postmitotic ganglion cells of the retina. Calretinin is observed in the ganglion and amacrine cells of the retina in neurons of different tectal bands and in axons of retinofugal projections. GFAP is localised in the endfeet of Müller cells and in radial processes of the optic tectum after hatching. A transient expression of GFAP in the optic nerve, coinciding with the arrival of the first calretinin-immunoreactive optic axons, is observed. As axonal growth occurs in these regions of the zebrafish visual pathway (retina and optic tectum) throughout the lifespan, a relationship between GFAP expression and the correct arrangement of the first optic axons may exist. In conclusion we provide valuable neuroanatomical data about the best characterised sensorial pathway to be used in further studies such as teratology and toxicology.

  2. Osteopontin inhibits osmotic swelling of retinal glial (Müller) cells by inducing release of VEGF.

    PubMed

    Wahl, V; Vogler, S; Grosche, A; Pannicke, T; Ueffing, M; Wiedemann, P; Reichenbach, A; Hauck, S M; Bringmann, A

    2013-08-29

    Osmotic swelling of retinal neurons and glial cells is an important pathogenic factor of retinal edema formation. Here, we show that the neuroprotective factor osteopontin (OPN), which is released from retinal glial (Müller) cells after stimulation of the cells with glial cell line-derived neurotrophic factor (Del Río et al., 2011, Glia 59:821-832), inhibits the swelling of rat Müller cells induced by hypoosmotic exposure of retinal slices in the presence of barium ions and H₂O₂, respectively, and in slices of postischemic retinas. OPN did not inhibit the hypoosmotic swelling of bipolar cells in slices of control and postischemic retinas. The inhibitory effect of OPN on Müller cell swelling was dose-dependent, with a half-maximal effect at ∼0.6 ng/ml. The effect of OPN was abrogated in the presence of pharmacological blockers of vascular endothelial growth factor (VEGF) receptor-2, metabotropic glutamate receptors, and purinergic receptors (P2Y₁, adenosine A1 receptors), as well as of a neutralizing anti-VEGF antibody. The data suggest that OPN induces the release of VEGF, glutamate, ATP, and adenosine from Müller cells. The effect of OPN was also prevented by blockers of voltage-gated sodium channels (tetrodotoxin), T-type voltage-gated calcium channels (kurtoxin), potassium channels (clofilium), and chloride channels 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). The swelling-inhibitory effect of OPN was dependent on intracellular calcium signaling, activation of phospholipase C and protein kinase C, and vesicular exocytosis of glutamate. In retinal slices, Müller glial cells display immunoreactivity of OPN. The data suggest that Müller cell-derived OPN has (in addition to the effects on photoreceptors and retinal neurons) autocrine effects. The neuroprotective effects of OPN may be in part mediated by the prevention of cytotoxic Müller cell swelling and the release of VEGF and adenosine from Müller cells.

  3. Codeine-induced hyperalgesia and allodynia: investigating the role of glial activation

    PubMed Central

    Johnson, J L; Rolan, P E; Johnson, M E; Bobrovskaya, L; Williams, D B; Johnson, K; Tuke, J; Hutchinson, M R

    2014-01-01

    Chronic morphine therapy has been associated with paradoxically increased pain. Codeine is a widely used opioid, which is metabolized to morphine to elicit analgesia. Prolonged morphine exposure exacerbates pain by activating the innate immune toll-like receptor-4 (TLR4) in the central nervous system. In silico docking simulations indicate codeine also docks to MD2, an accessory protein for TLR4, suggesting potential to induce TLR4-dependent pain facilitation. We hypothesized codeine would cause TLR4-dependent hyperalgesia/allodynia that is disparate from its opioid receptor-dependent analgesic rank potency. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests at days 0, 3 and 5 in mice receiving intraperitoneal equimolar codeine (21 mg kg−1), morphine (20 mg kg−1) or saline, twice daily. This experiment was repeated in animals with prior partial nerve injury and in TLR4 null mutant mice. Interventions with interleukin-1 receptor antagonist (IL-1RA) and glial-attenuating drug ibudilast were assessed. Analyses of glial activation markers (glial fibrillary acid protein and CD11b) in neuronal tissue were conducted at the completion of behavioural testing. Despite providing less acute analgesia (P=0.006), codeine induced similar hotplate hyperalgesia to equimolar morphine vs saline (−9.5 s, P<0.01 and −7.3 s, P<0.01, respectively), suggesting codeine does not rely upon conversion to morphine to increase pain sensitivity. This highlights the potential non-opioid receptor-dependent nature of codeine-enhanced pain sensitivity—although the involvement of other codeine metabolites cannot be ruled out. IL-1RA reversed codeine-induced hyperalgesia (P<0.001) and allodynia (P<0.001), and TLR4 knock-out protected against codeine-induced changes in pain sensitivity. Glial attenuation with ibudilast reversed codeine-induced allodynia (P<0.001), and thus could be investigated further as potential treatment for codeine-induced pain

  4. Communication between neuronal somata and satellite glial cells in sensory ganglia.

    PubMed

    Huang, Li-Yen M; Gu, Yanping; Chen, Yong

    2013-10-01

    Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions. "What are the mechanisms underlying the neuronal soma and SGC communication in sensory ganglia?" and "how do tissue or nerve injuries affect the communication?" are the main questions addressed in this review.

  5. In silico identification of novel hevein-like peptide precursors.

    PubMed

    Porto, William F; Souza, Valéria A; Nolasco, Diego O; Franco, Octávio L

    2012-11-01

    Lectins are proteins with ability to bind reversibly and non-enzymatically to a specific carbohydrate. They are involved in numerous biological processes and show enormous biotechnological potential. Among plant lectins, the hevein domain is extremely common, being observed in several kinds of lectins. Moreover, this domain is also observed in an important class of antimicrobial peptides named hevein-like peptides. Due to higher cysteine residues conservation, hevein-like peptides could be mined among the sequence databases. By using the pattern CX(4,5)CC[GS]X(2)GXCGX[GST]X(2,3)[FWY]C[GS]X[AGS] novel hevein-like peptide precursors were found from three different plants: Oryza sativa, Vitis vinifera and Selaginella moellendorffii. In addition, an hevein-like peptide precursor from the phytopathogenic fungus Phaeosphaeria nodorum was also identified. The molecular models indicate that they have the same scaffold as others, composed of an antiparallel β-sheet and short helices. Nonetheless, the fungal hevein-like peptide probably has a different disulfide bond pattern. Despite this difference, the complexes between peptide and N,N,N-triacetylglucosamine are stable, according to molecular dynamics simulations. This is the first report of an hevein-like peptide from an organism outside the plant kingdom. The exact role of an hevein-like peptide in the fungal biology must be clarified, while in plants they are clearly involved in plant defense. In summary, data here reported clear shows that an in silico strategy could lead to the identification of novel hevein-like peptides that could be used as biotechnological tools in the fields of health and agribusiness.

  6. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans.

    PubMed

    Sirisi, Sònia; Folgueira, Mónica; López-Hernández, Tania; Minieri, Laura; Pérez-Rius, Carla; Gaitán-Peñas, Héctor; Zang, Jingjing; Martínez, Albert; Capdevila-Nortes, Xavier; De La Villa, Pedro; Roy, Upasana; Alia, A; Neuhauss, Stephan; Ferroni, Stefano; Nunes, Virginia; Estévez, Raúl; Barrallo-Gimeno, Alejandro

    2014-10-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by myelin vacuolization and caused by mutations in MLC1 or GLIALCAM. Patients with recessive mutations in either MLC1 or GLIALCAM show the same clinical phenotype. It has been shown that GLIALCAM is necessary for the correct targeting of MLC1 to the membrane at cell junctions, but its own localization was independent of MLC1 in vitro. However, recent studies in Mlc1(-/-) mice have shown that GlialCAM is mislocalized in glial cells. In order to investigate whether the relationship between Mlc1 and GlialCAM is species-specific, we first identified MLC-related genes in zebrafish and generated an mlc1(-/-) zebrafish. We have characterized mlc1(-/-) zebrafish both functionally and histologically and compared the phenotype with that of the Mlc1(-/-) mice. In mlc1(-/-) zebrafish, as in Mlc1(-/-) mice, Glialcam is mislocalized. Re-examination of a brain biopsy from an MLC patient indicates that GLIALCAM is also mislocalized in Bergmann glia in the cerebellum. In vitro, impaired localization of GlialCAM was observed in astrocyte cultures from Mlc1(-/-) mouse only in the presence of elevated potassium levels, which mimics neuronal activity. In summary, here we demonstrate an evolutionary conserved role for MLC1 in regulating glial surface levels of GLIALCAM, and this interrelationship explains why patients with mutations in either gene (MLC1 or GLIALCAM) share the same clinical phenotype.

  7. Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells.

    PubMed

    Karl, Anett; Wurm, Antje; Pannicke, Thomas; Krügel, Katja; Obara-Michlewska, Marta; Wiedemann, Peter; Reichenbach, Andreas; Albrecht, Jan; Bringmann, Andreas

    2011-02-01

    High blood ammonia, elevated glutamine, and hyponatremia are pathogenic factors contributing to astrocytic swelling and brain edema in liver failure. We investigated the effects of hypoosmolarity, ammonia, and glutamine on the induction of glial cell swelling in freshly isolated slices of the rat retina. Glutamine, but not ammonia or hypoosmolarity per se, evoked a rapid (within one minute) swelling of retinal glial (Müller) cell bodies under hypoosmotic conditions. Under isoosmotic conditions, glutamine evoked a delayed swelling after 10 min of exposure. The effect of glutamine was concentration-dependent, with half-maximal and maximal effects at ∼ 0.1 and 0.5 mM. Glutamine in hypoosmotic solution induced a dissipation of the mitochondrial membrane potential. The effects on the mitochondrial membrane potential and the glial soma size were reduced by (i) agents which inhibit the transfer of glutamine into mitochondria and its hydrolysis there, (ii) inhibition of the mitochondrial permeability transition, (iii) inhibitors of oxidative-nitrosative stress, and (iv) inhibitors of phospholipase A(2) and cyclooxygenase. Glutamine-induced glial swelling was also prevented by ATP and adenosine, acting at adenosine A(1) receptors. The data suggest that hypoosmolarity accelerates the swelling-inducing effect of glutamine on retinal glial cells, and that swelling induction by glutamine is mediated by inducing oxidative-nitrosative stress, inflammatory lipid mediators, and mitochondrial dysfunction.

  8. TRAP-seq Profiling and RNAi-Based Genetic Screens Identify Conserved Glial Genes Required for Adult Drosophila Behavior

    PubMed Central

    Ng, Fanny S.; Sengupta, Sukanya; Huang, Yanmei; Yu, Amy M.; You, Samantha; Roberts, Mary A.; Iyer, Lakshmanan K.; Yang, Yongjie; Jackson, F. Rob

    2016-01-01

    Although, glial cells have well characterized functions in the developing and mature brain, it is only in the past decade that roles for these cells in behavior and plasticity have been delineated. Glial astrocytes and glia-neuron signaling, for example, are now known to have important modulatory functions in sleep, circadian behavior, memory and plasticity. To better understand mechanisms of glia-neuron signaling in the context of behavior, we have conducted cell-specific, genome-wide expression profiling of adult Drosophila astrocyte-like brain cells and performed RNA interference (RNAi)-based genetic screens to identify glial factors that regulate behavior. Importantly, our studies demonstrate that adult fly astrocyte-like cells and mouse astrocytes have similar molecular signatures; in contrast, fly astrocytes and surface glia—different classes of glial cells—have distinct expression profiles. Glial-specific expression of 653 RNAi constructs targeting 318 genes identified multiple factors associated with altered locomotor activity, circadian rhythmicity and/or responses to mechanical stress (bang sensitivity). Of interest, 1 of the relevant genes encodes a vesicle recycling factor, 4 encode secreted proteins and 3 encode membrane transporters. These results strongly support the idea that glia-neuron communication is vital for adult behavior. PMID:28066175

  9. Nozzle designs with pitch precursor ablatives

    NASA Technical Reports Server (NTRS)

    Blevins, H. R.; Bedard, R. J.

    1976-01-01

    Recent developments in carbon phenolic ablatives for solid rocket motor nozzles have yielded a pitch precursor carbon fiber offering significant raw material availability and cost saving advantages as compared to conventional rayon precursor material. This paper discusses the results of an experimental program conducted to assess the thermal performance and characterize the thermal properties of pitch precursor carbon phenolic ablatives. The end result of this program is the complete thermal characterization of pitch fabric, pitch mat, hybrid pitch/rayon fabric and pitch mat molding compound. With these properties determined an analytic capability now exists for predicting the thermal performance of these materials in rocket nozzle liner applications. Further planned efforts to verify material performance and analytical prediction procedures through actual rocket motor firings are also discussed.

  10. Sequestration and Transport of Lignin Monomeric Precursors

    SciTech Connect

    Liu, C.J.; Miao, Y.-C.; Zhang, K.-W.

    2011-01-18

    Lignin is the second most abundant terrestrial biopolymer after cellulose. It is essential for the viability of vascular plants. Lignin precursors, the monolignols, are synthesized within the cytosol of the cell. Thereafter, these monomeric precursors are exported into the cell wall, where they are polymerized and integrated into the wall matrix. Accordingly, transport of monolignols across cell membranes is a critical step affecting deposition of lignin in the secondarily thickened cell wall. While the biosynthesis of monolignols is relatively well understood, our knowledge of sequestration and transport of these monomers is sketchy. In this article, we review different hypotheses on monolignol transport and summarize the recent progresses toward the understanding of the molecular mechanisms underlying monolignol sequestration and transport across membranes. Deciphering molecular mechanisms for lignin precursor transport will support a better biotechnological solution to manipulate plant lignification for more efficient agricultural and industrial applications of cell wall biomass.

  11. Precursors prior to type IIn supernova explosions are common: Precursor rates, properties, and correlations

    SciTech Connect

    Ofek, Eran O.; Steinbok, Aviram; Arcavi, Iair; Gal-Yam, Avishay; Tal, David; Ben-Ami, Sagi; Yaron, Ofer; Sullivan, Mark; Shaviv, Nir J.; Kulkarni, Shrinivas R.; Nugent, Peter E.; Kasliwal, Mansi M.; Cenko, S. Bradley; Silverman, Jeffrey M.

    2014-07-10

    There is a growing number of Type IIn supernovae (SNe) which present an outburst prior to their presumably final explosion. These precursors may affect the SN display, and are likely related to poorly charted phenomena in the final stages of stellar evolution. By coadding Palomar Transient Factory (PTF) images taken prior to the explosion, here we present a search for precursors in a sample of 16 Type IIn SNe. We find five SNe IIn that likely have at least one possible precursor event (PTF 10bjb, SN 2010mc, PTF 10weh, SN 2011ht, and PTF 12cxj), three of which are reported here for the first time. For each SN we calculate the control time. We find that precursor events among SNe IIn are common: at the one-sided 99% confidence level, >50% of SNe IIn have at least one pre-explosion outburst that is brighter than 3 × 10{sup 7} L{sub ☉} taking place up to 1/3 yr prior to the SN explosion. The average rate of such precursor events during the year prior to the SN explosion is likely ≳ 1 yr{sup –1}, and fainter precursors are possibly even more common. Ignoring the two weakest precursors in our sample, the precursors rate we find is still on the order of one per year. We also find possible correlations between the integrated luminosity of the precursor and the SN total radiated energy, peak luminosity, and rise time. These correlations are expected if the precursors are mass-ejection events, and the early-time light curve of these SNe is powered by interaction of the SN shock and ejecta with optically thick circumstellar material.

  12. 2. View of Clear Creek Bridge railing and understructure, looking ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. View of Clear Creek Bridge railing and under-structure, looking northwest. - Zion-Mount Carmel Highway, 62-foot Concrete Arch Pine Creek Bridge, Spanning Clear Creek, Springdale, Washington County, UT

  13. Polymeric precursors for fibers and matrices

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    1992-01-01

    Candidate polymeric precursors for ceramic fiber and matrix processing are discussed, with a view to the advantages and disadvantages of this approach relative to existing alternatives. The properties of ceramic products thus derived are noted to strongly depend on the molecular weight and structure of the starting polymer; in particular, the ceramic's composition and morphology are dependent on the character and extent of crosslinking, as well as on the path of pyrolysis. While large and complex structural ceramic components may ultimately be obtainable by these means, the polymer-precursor method is still in its developmental infancy.

  14. Nonlinear magnetohydrodynamics of edge localized mode precursors

    NASA Astrophysics Data System (ADS)

    Guo, Z. B.; Wang, Lu; Wang, X. G.

    2015-02-01

    A possible origin of edge-localized-mode (ELM) precursors based on nonlinear ideal peeling-ballooning mode is reported. Via nonlinear variational principle, a nonlinear evolution equation of the radial displacement is derived and solved, analytically. Besides an explosive growth in the initial nonlinear phase, it is found that the local displacement evolves into an oscillating state in the developed nonlinear phase. The nonlinear frequency of the ELM precursors scales as ωpr e˜x1 /3ξ̂ψ,i n 2 /3n , with x position in radial direction, ξ̂ ψ,i n strength of initial perturbation, and n toroidal mode number.

  15. 31 CFR 50.12 - Clear and conspicuous disclosure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirement to provide clear and conspicuous disclosure as described in § 50.10 through use of appropriate... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Clear and conspicuous disclosure. 50... INSURANCE PROGRAM Disclosures as Conditions for Federal Payment § 50.12 Clear and conspicuous disclosure....

  16. 76 FR 16587 - Risk Management Requirements for Derivatives Clearing Organizations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-24

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 39 RIN 3038-AC98 Risk Management Requirements for Derivatives Clearing Organizations... require derivatives clearing organizations (DCOs) to report end-of-day positions for each clearing...

  17. 75 FR 77576 - General Regulations and Derivatives Clearing Organizations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-13

    ... COMMISSION 17 CFR Parts 1 and 39 RIN 3038-AC98 General Regulations and Derivatives Clearing Organizations... amendments would establish the regulatory standards for compliance with derivatives clearing organization... ``clearing organization,'' and to add definitions for certain other terms. DATES: Submit comments on...

  18. Regulatory role of a neurotransmitter (5-HT) on glial Na+/K(+)-ATPase in the rat brain.

    PubMed

    Mercado, R; Hernández, J

    1992-07-01

    In the present work we studied the effect of serotonin (5-HT) on the kinetics of Na+/K(+)-ATPase in subcellular preparations of the cerebral cortex from male Wistar rats using various concentrations of ATP and K+ with and without added 5-HT. Also we studied the effect of 5-HT on the enzyme in glial or neuronal preparations. The results indicated that there was a significant increase (P < 0.05) of the Vmax in the presence of 5-HT in the whole tissue preparation (homogenate) but not in the subcellular fractions, suggesting that the interaction could be preferentially with the glial pump. Further results supported that this was the case since activation by 5-HT was mainly in the glial preparations. Kinetic data and the binding of [3H]ouabain supported that the enzyme is activated by 5-HT through the exposure of more enzymatic active sites.

  19. Inflammatory glial activation in the brain of a patient with hereditary sensory neuropathy type 1 with deafness and dementia.

    PubMed

    Hojo, Kaori; Kawamata, Toshio; Tanaka, Chikako; Maeda, Kiyoshi

    2004-09-09

    The brain of a patient with hereditary sensory neuropathy type 1 (HSN-1) associated with sensorineural deafness and early-onset dementia was neuropathologically investigated. Widespread neuronal degeneration in cerebral neocortex, hippocampus and basal ganglia was revealed, accounting for the clinical features. Loss of neurons with ballooning of residual neurons was remarkable in the hippocampus and frontal, parietal, and occipital lobes. Neuronal degeneration in these regions was accompanied by axonal dystrophy and glial reactions such as microgliosis and astrocytosis, however, only glial responses were prominent in the basal ganglia, brain-stem and cerebellum with mild neuronal loss. These results indicate that the widespread neuronal degeneration may be accelerated by inflammatory processes including glial activation in the brain of a patient with HSN-1 associated with deafness and dementia.

  20. Microarray analysis of glial cells resistant to JCV infection suggests a correlation between viral infection and inflammatory cytokine gene expression

    PubMed Central

    Manley, Kate; Gee, Gretchen V; Simkevich, Carl P; Sedivy, John M; Atwood, Walter J

    2007-01-01

    The human polyomavirus, JCV, has a highly restricted tropism and primarily infects glial cells. The mechanisms restricting infection of cells by JCV are poorly understood. Previously we developed and described a glial cell line that was resistant to JCV infection with the aim of using these cells to identify factors that determine JCV tropism. Gene expression profiling of susceptible and resistant glial cells revealed a direct correlation between the expression of inflammatory cytokines and susceptibility to JCV infection. This correlation manifested at the level of viral gene transcription. Previous studies have suggested a link between an increase in cytokine gene expression in HIV patients and the development of PML and these data support this hypothesis. PMID:17555786

  1. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons.

    PubMed

    Orellana, Juan A; Moraga-Amaro, Rodrigo; Díaz-Galarce, Raúl; Rojas, Sebastián; Maturana, Carola J; Stehberg, Jimmy; Sáez, Juan C

    2015-01-01

    Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippocampal apical dendrites, loss of synapses and neuronal death. Under neuro-inflammatory conditions, we recently unveiled a sequential activation of glial cells that release ATP and glutamate via hemichannels inducing neuronal death due to activation of neuronal NMDA/P2X7 receptors and pannexin1 hemichannels. In the present work, we studied if stress-induced glia activation is associated to changes in hemichannel activity. To this end, we compared hemichannel activity of brain cells after acute or chronic restraint stress in mice. Dye uptake experiments in hippocampal slices revealed that acute stress induces opening of both Cx43 and Panx1 hemichannels in astrocytes, which were further increased by chronic stress; whereas enhanced Panx1 hemichannel activity was detected in microglia and neurons after acute/chronic and chronic stress, respectively. Moreover, inhibition of NMDA/P2X7 receptors reduced the chronic stress-induced hemichannel opening, whereas blockade of Cx43 and Panx1 hemichannels fully reduced ATP and glutamate release in hippocampal slices from stressed mice. Thus, we propose that gliotransmitter release through hemichannels may participate in the pathogenesis of stress-associated psychiatric disorders and possibly depression.

  2. Hypoxia-like tissue injury and glial response contribute to Balo concentric lesion development

    PubMed Central

    Takai, Yoshiki; Misu, Tatsuro; Nishiyama, Shuhei; Ono, Hirohiko; Kuroda, Hiroshi; Nakashima, Ichiro; Saito, Ryuta; Kanamori, Masayuki; Sonoda, Yukihiko; Kumabe, Toshihiro; Mugikura, Shunji; Watanabe, Mika; Fujihara, Kazuo

    2016-01-01

    Objective: To clarify the pathogenic factors and mechanisms underlying the development of concentric demyelinating lesions in Balo disease. Methods: We conducted serial clinical, MRI, and histopathologic assessments of concentric lesion formation in a case of relapsing Balo disease. Results: The patient experienced 2 attacks caused by left parietal and left frontal lesions in 5 years. In MRI findings from both episodes of expanding lesions, there were diffusion-restricted rings that antedated the appearance of gadolinium enhancement; subsequently, typical concentric T2 lesions appeared concurrently with the disappearance of this enhancement. Histopathologic examinations of biopsied brain tissues revealed definite concentric demyelinating layers typical of Balo disease with massive macrophage infiltration but preserved axons. Numerous hypertrophic astrocytes were observed beyond the edges of and within the demyelinating layers. The expression of hypoxia-inducible factor-1α, a protein related to hypoxia-induced tissue preconditioning that contributes to survival and protection against further hypoxia-like injury, was upregulated primarily in glial cells located beyond the edge of the demyelinating layers but was also elevated in hypertrophic astrocytes on the inner sides of resected lesions and in oligodendrocytes in nondemyelinating layers. In addition, these astrocytes expressed CC motif chemokine 2 and/or interleukin-1β, which are inducible by hypoxia-inducible factor-1α and potentially promote demyelination. Conclusions: Our study suggests that a unique interplay between hypoxia-induced tissue preconditioning and proinflammatory cytokines derived from glial cells may contribute to the development of concentric demyelinating lesions in Balo disease. PMID:27733565

  3. AMPA receptor mediated D-serine release from retinal glial cells

    PubMed Central

    Sullivan, Steve J.; Miller, Robert F.

    2010-01-01

    The NMDA receptor coagonist D-serine is important in a number of different processes in the central nervous system, ranging from synaptic plasticity to disease states, including schizophrenia. D-serine appears to be the major coagonist acting on retinal ganglion cell NMDA receptors, but the cell type from which it originates and whether its release can be modulated by activity are unknown. In this study, we utilized a mutant mouse line with elevated D-serine to investigate this question. Direct measurements of extracellular D-serine using capillary electrophoresis demonstrate that D-serine can be released from the intact mouse retina through an AMPA receptor dependent mechanism. AMPA-evoked D-serine release persisted in the presence of a cocktail of neural inhibitors but was abolished after administration of a glial toxin. These findings provide the first evidence that extracellular D-serine levels in the retina can be modulated, and that such modulation is contingent upon glial cell activity. PMID:20969576

  4. Glial glucocorticoid receptors in aged Fisher 344 (F344) and F344/Brown Norway rats

    PubMed Central

    Kasckow, J; Xiao, C; Herman, JP

    2009-01-01

    Glucocorticoid receptors (GR) regulate glial function, and changes in astrocyte gene expression are implicated in age-related pathology. We evaluated changes in astroglial GR expression in two strains of rats – Fisher 344 (F344; 4, 12 and 24 months) and F344/Brown Norway strain (F344/BN; 4, 12 and 30 months). In both strains basal levels of corticosterone were higher in the oldest groups of rats. Age-related increases in GR (+) astrocytes but not the percent of astrocytes expressing GR were observed in the hippocampus CA1 region in F344 rats. Age-related decreases in CA1 GR (+) astrocytes and the percentage of GR (+) astrocytes were observed in the F344/BN strain only. Similar strain-specific changes were observed in the dentate gyrus. In the hypothalamic paraventricular nucleus: 1) F344 rats exhibited significant decreases in the overall number of glial profiles with age, 2) F344/BN rats exhibited decreases in the numbers of GR (+) astrocytes with aging and 3) the proportion of GR (+) astrocytes decreased in older F344/BN, but not F344 rats. Overall, the data demonstrate age- and strain-related alterations in GR astrocytic expression that may explain unique phenotypic differences in brain function observed in both strains. PMID:19249343

  5. Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development

    PubMed Central

    Hao, Marlene M.; Capoccia, Elena; Cirillo, Carla; Boesmans, Werend; Vanden Berghe, Pieter

    2017-01-01

    S100B is expressed in various types of glial cells and is involved in regulating many aspects of their function. However, little is known about its role during nervous system development. In this study, we investigated the effect of inhibiting the onset of S100B synthesis in the development of the enteric nervous system, a network of neurons and glia located in the wall of the gut that is vital for control of gastrointestinal function. Intact gut explants were taken from embryonic day (E)13.5 mice, the day before the first immunohistochemical detection of S100B, and cultured in the presence of arundic acid, an inhibitor of S100B synthesis, for 48 h. The effects on Sox10-immunoreactive enteric neural crest progenitors and Hu-immunoreactive enteric neurons were then analyzed. Culture in arundic acid reduced the proportion of Sox10+ cells and decreased cell proliferation. There was no change in the density of Hu+ enteric neurons, however, a small population of cells exhibited atypical co-expression of both Sox10 and Hu, which was not observed in control cultures. Addition of exogenous S100B to the cultures did not change Sox10+ cell numbers. Overall, our data suggest that cell-intrinsic intracellular S100B is important for maintaining Sox10 and proliferation of the developing enteric glial lineage. PMID:28280459

  6. Hormonal modulators of glial ABCA1 and apoE levels[S

    PubMed Central

    Fan, Jianjia; Shimizu, Yoko; Chan, Jeniffer; Wilkinson, Anna; Ito, Ayaka; Tontonoz, Peter; Dullaghan, Edie; Galea, Liisa A. M.; Pfeifer, Tom; Wellington, Cheryl L.

    2013-01-01

    Apolipoprotein E (apoE) is the major lipid carrier in the central nervous system. As apoE plays a major role in the pathogenesis of Alzheimer disease (AD) and also mediates repair pathways after several forms of acute brain injury, modulating the expression, secretion, or function of apoE may provide potential therapeutic approaches for several neurological disorders. Here we show that progesterone and a synthetic progestin, lynestrenol, significantly induce apoE secretion from human CCF-STTG1 astrocytoma cells, whereas estrogens and the progesterone metabolite allopregnanolone have negligible effects. Intriguingly, lynestrenol also increases expression of the cholesterol transporter ABCA1 in CCF-STTG1 astrocytoma cells, primary murine glia, and immortalized murine astrocytes that express human apoE3. The progesterone receptor inhibitor RU486 attenuates the effect of progestins on apoE expression in CCF-STTG1 astrocytoma cells but has no effect on ABCA1 expression in all glial cell models tested, suggesting that the progesterone receptor (PR) may participate in apoE but does not affect ABCA1 regulation.These results suggest that selective reproductive steroid hormones have the potential to influence glial lipid homeostasis through liver X receptor-dependent and progesterone receptor-dependent pathways. PMID:23999864

  7. Grafted bone marrow stromal cells: a contributor to glial repair after spinal cord injury.

    PubMed

    Zhang, Li-Xin; Yin, Yan-Mei; Zhang, Zhi-Qiang; Deng, Ling-Xiao

    2015-06-01

    In the CNS, astrocytes, oligodendrocytes and microglias are involved in not only development but also pathology such as spinal cord injury (SCI). Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Bone marrow stromal cells (BMSCs) represent a new therapeutic approach for SCI by enabling improved sensory and motor functions in animal models. Although transdifferentiation to spinal neurons was poor, because of their pleiotropic nature, the protective effects of BMSCs are broad and are primarily mediated through modulation of transdifferentiation into host spinal glial components. Transplantation of BMSCs can positively alter the spinal microenvironment and enhance recovery. The objective of this review is to discuss these and other related mechanisms. Since BMSCs transplantation has been applied in other clinical fields, we hope to provide useful clues for the clinical application of BMSCs to treat the SCI in the near future.

  8. Bioengineered 3D Glial Cell Culture Systems and Applications for Neurodegeneration and Neuroinflammation.

    PubMed

    Watson, P Marc D; Kavanagh, Edel; Allenby, Gary; Vassey, Matthew

    2017-02-01

    Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures. Given the complexity of the environment from which cells originate, and their various cell-cell and cell-matrix interactions, it is important to develop models that can be controlled and reproducible for drug discovery. 3D cell models have now been developed for almost all CNS cell types, including neurons, astrocytes, microglia, and oligodendrocyte cells. This review will highlight a number of current and emerging techniques for the culture of astrocytes and microglia, glial cell types with a critical role in neurodegenerative and neuroinflammatory conditions. We describe recent advances in glial cell culture using electrospun polymers and hydrogel macromolecules, and highlight how these novel culture environments influence astrocyte and microglial phenotypes in vitro, as compared to traditional 2D systems. These models will be explored to illuminate current trends in the techniques used to create 3D environments for application in research and drug discovery focused on astrocytes and microglial cells.

  9. Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling.

    PubMed

    Thyssen, Anne; Hirnet, Daniela; Wolburg, Hartwig; Schmalzing, Günther; Deitmer, Joachim W; Lohr, Christian

    2010-08-24

    Neurotransmitter release generally is considered to occur at active zones of synapses, and ectopic release of neurotransmitters has been demonstrated in a few instances. However, the mechanism of ectopic neurotransmitter release is poorly understood. We took advantage of the intimate morphological and functional proximity of olfactory receptor axons and specialized glial cells, olfactory ensheathing cells (OECs), to study ectopic neurotransmitter release. Axonal stimulation evoked purinergic and glutamatergic Ca(2+) responses in OECs, indicating ATP and glutamate release. In axons expressing synapto-pHluorin, stimulation evoked an increase in synapto-pHluorin fluorescence, indicative of vesicle fusion. Transmitter release was dependent on Ca(2+) and could be inhibited by bafilomycin A1 and botulinum toxin A. Ca(2+) transients in OECs evoked by ATP, axonal stimulation, and laser photolysis of NP-EGTA resulted in constriction of adjacent blood vessels. Our results indicate that ATP and glutamate are released ectopically by vesicles along axons and mediate neurovascular coupling via glial Ca(2+) signaling.

  10. Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia.

    PubMed

    Blum, E; Procacci, P; Conte, V; Sartori, P; Hanani, M

    2017-01-01

    Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopy was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injectio