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  1. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether......Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...

  2. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...

  3. Effect of different densities of silver nanoparticles on neuronal growth

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    Nissan, Ifat [Bar-Ilan University, Department of Chemistry (Israel); Schori, Hadas [Bar-Ilan University, Faculty of Engineering (Israel); Lipovsky, Anat [Bar-Ilan University, Department of Chemistry (Israel); Alon, Noa [Bar-Ilan University, Faculty of Engineering (Israel); Gedanken, Aharon, E-mail: gedanken@biu.ac.il [Bar-Ilan University, Department of Chemistry (Israel); Shefi, Orit, E-mail: orit.shefi@biu.ac.il [Bar-Ilan University, Faculty of Engineering (Israel)

    2016-08-15

    Nerve regeneration has become a subject of great interest, and much effort is devoted to the design and manufacturing of effective biomaterials. In this paper, we report the capability of surfaces coated with silver nanoparticles (AgNPs) to serve as platforms for nerve regeneration. We fabricated substrates coated with silver nanoparticles at different densities using sonochemistry, and grew neuroblastoma cells on the AgNPs. The effect of the different densities on the development of the neurites during the initiation and elongation growth phases was studied. We found that the AgNPs function as favorable anchoring sites for the neuroblastoma cells, significantly enhancing neurite outgrowth. One of the main goals of this study is to test whether the enhanced growth of the neurites is due to the mere presence of AgNPs or whether their topography also plays a vital role. We found that this phenomenon was repeated for all the tested densities, with a maximal effect for the substrates that are coated with 45 NPs/μm{sup 2}. We also studied the amount of reactive oxygen spices (ROS) in the presence of AgNPs as indicator of cell activation. Our results, combined with the well-known antibacterial effects of AgNPs, suggest that substrates coated with AgNP are attractive nanomaterials—with dual activity—for neuronal repair studies and therapeutics.Graphical Abstract.

  4. Neuronal Survival, Morphology and Outgrowth of Spiral Ganglion Neurons Using a Defined Growth Factor Combination.

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    Jana Schwieger

    Full Text Available The functionality of cochlear implants (CI depends, among others, on the number and excitability of surviving spiral ganglion neurons (SGN. The spatial separation between the SGN, located in the bony axis of the inner ear, and the CI, which is inserted in the scala tympani, results in suboptimal performance of CI patients and may be decreased by attracting the SGN neurites towards the electrode contacts. Neurotrophic factors (NTFs can support neuronal survival and neurite outgrowth.Since brain-derived neurotrophic factor (BDNF is well known for its neuroprotective effect and ciliary neurotrophic factor (CNTF increases neurite outgrowth, we evaluated if the combination of BDNF and CNTF leads to an enhanced neuronal survival with extended neurite outgrowth. Both NTFs were added in effective high concentrations (BDNF 50 ng/ml, CNTF 100 ng/ml, alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours.The neuronal survival and neurite outgrowth were significantly higher in SGN treated with the combination of the two NTFs compared to treatment with each factor alone. Additionally, with respect to the morphology, the combination of BDNF and CNTF leads to a significantly higher number of bipolar neurons and a decreased number of neurons without neurites in culture.The combination of BDNF and CNTF shows a great potential to increase the neuronal survival and the number of bipolar neurons in vitro and to regenerate retracted nerve fibers.

  5. Neuronal survival induced by neurotrophins requires calmodulin

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    Egea, Joaquim; Espinet, Carme; Soler, Rosa M.; Dolcet, Xavier; Yuste, Víctor J.; Encinas, Mario; Iglesias, Montserrat; Rocamora, Nativitat; Comella, Joan X.

    2001-01-01

    It has been reported that phosphoinositide 3-kinase (PI 3-kinase) and its downstream target, protein kinase B (PKB), play a central role in the signaling of cell survival triggered by neurotrophins (NTs). In this report, we have analyzed the involvement of Ca2+ and calmodulin (CaM) in the activation of the PKB induced by NTs. We have found that reduction of intracellular Ca2+ concentration or functional blockade of CaM abolished NGF-induced activation of PKB in PC12 cells. Similar results were obtained in cultures of chicken spinal cord motoneurons treated with brain-derived neurotrophic factor (BDNF). Moreover, CaM inhibition prevented the cell survival triggered by NGF or BDNF. This effect was counteracted by the transient expression of constitutive active forms of the PKB, indicating that CaM regulates NT-induced cell survival through the activation of the PKB. We have investigated the mechanisms whereby CaM regulates the activation of the PKB, and we have found that CaM was necessary for the proper generation and/or accumulation of the products of the PI 3-kinase in intact cells. PMID:11489918

  6. Concentration Dependent Actions of Glucocorticoids on Neuronal Viability and Survival

    NARCIS (Netherlands)

    Ábrahám, István M.; Meerlo, Peter; Luiten, Paul G.M.

    2006-01-01

    A growing body of evidence based on experimental data demonstrates that glucocorticoids (GCs) can play a potent role in the survival and death of neurons. However, these observations reflect paradoxical features of GCs, since these adrenal stress hormones are heavily involved in both

  7. Survival of adhering cortical neurons on polyethylenimine micropatterns

    NARCIS (Netherlands)

    Ruardij, T.G.; Goedbloed, M.H.; Rutten, Wim

    2001-01-01

    The influence of neuron-adhesive pattern geometry on long-term survival of cortical neural tissue (rat brain) was studied over a time period of 15 days. Microwells (depth 0.5 /spl mu/m) with diameters of 25, 50, 100 and 150 /spl mu/m and inter-microwell distances of 15, 30, 60 and 90 /spl mu/m, were

  8. Progranulin is expressed within motor neurons and promotes neuronal cell survival

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    Kay Denis G

    2009-10-01

    Full Text Available Abstract Background Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival. Results In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months. This is mediated at least in part through

  9. Vasoactive intestinal peptide and nitric oxide promote survival of adult rat myenteric neurons in culture

    DEFF Research Database (Denmark)

    Sandgren, Katarina; Lin, Zhong; Svenningsen, Åsa Fex

    2003-01-01

    adaptation. The aim of this study was to evaluate whether VIP and nitric oxide (NO) influence survival of cultured, dissociated myenteric neurons. Neuronal survival was evaluated after 0, 4, and 8 days in culture. Influence of VIP and NO on neuronal survival was examined after culturing in the presence...

  10. Sensory neurons in culture: Changing requirements for survival factors during embryonic development

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    Barde, Y.-A.; Edgar, D.; Thoenen, H.

    1980-01-01

    The effect of nerve growth factor (NGF) and medium conditioned by glioma cells (GCM) on the survival of chicken sensory neurons in culture was investigated. Neurons were isolated from embryos 8 days (E8) to 16 days (E16) old and the proportion of surviving neurons was determined after 2 days in culture. In the absence of NGF or GCM, essentially no neurons survived at any age. In the presence of NGF, survival increased from 25% of the neurons at E8 to 40% between E10 and E12 and then decreased to background level (5%) at E16. In contrast, in the presence of GCM, survival increased continuously from 10% of the neurons at E8 to 75% at E16. At early developmental stages, the effect of NGF and GCM together was greater than the sum of their individual effects: at E8, about 80% of the neurons survived, double the number expected for a simple additive effect. Thus, a significant proportion of chicken neurons from dorsal root ganglia require both NGF and GCM for survival, and this may well include neurons from the ventro-lateral population, which do not respond to NGF alone. As neurons matured, the double requirement progressively decreased and, by E16, NGF no longer increased the number of neurons over that surviving in response to GCM alone. The facts that rat brain extracts mimicked the effect of GCM and that the potency of the brain extracts of rat in the postnatal period increased in parallel with the development of the glial cells suggest that glial cells produce a factor(s) both immunologically and functionally different from NGF which supports the survival of sensory neurons. Images PMID:6928668

  11. The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus

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    Farzaneh Bagheri-abassi

    2015-07-01

    Full Text Available Objective(s:Silver nanoparticles (Ag-NPs are used widely in bedding, water purification, tooth paste and toys. These nanoparticles can enter into the body and move into the hippocampus. The aim of this study was to investigate the neurotoxicity of silver nanoparticles in the adult rat hippocampus. Materials and Methods:12 male Wistar rats were randomly divided into two experimental and control groups (6 rats in each group. Animals in the experimental group received Ag-NPs (30 mg/kg orally (gavage for 28 consecutive days. Control group in the same period was treated with distilled water via gavage. At the end of experiment, animals were deeply anesthetized, sacrificed, and their brains were collected from each group. Finally the brain sections were stained using toluidine blue and TUNEL. Then to compare the groups, dark neurons (DNs and apoptotic neurons were counted by morphometric method. Results: Results showed that the num­bers of DNs and apoptotic cells in the CA1, CA2, CA3, and dentate gyrus (DG of hippocampus significantly increased in the Ag-NPs group in comparison to the control group (P

  12. Survival and progression rates of large European silver eel Anguilla anguilla in late freshwater and early marine phases

    DEFF Research Database (Denmark)

    Aarestrup, Kim; Thorstad, Eva B.; Koed, Anders

    2010-01-01

    The population of European silver eel Anguilla anguilla has declined tremendously in the last decades. The cause of this decline is unknown, and it is necessary to investigate the migratory behaviour and survival rates of silver eels during the reproductive migration in order to understand...... was high in fresh water. However, 60% of eels were lost in the inner and outer fjord, supporting the hypothesis that mortality is large in the early phase of the marine migration and that fishing may be a major cause of mortality of silver eels. There was no indication that the slowest-migrating...... if the decline is related to factors acting during that migration. We estimated survival and progression rates of European silver eel migrating in the lower part of the River Gudenaa and during the first phase of the marine migration in the Randers Fjord in Denmark. Fifty migrating silver eel (total body length...

  13. Glial cell-line derived neurotrophic factor-dependent fusimotor neuron survival during development.

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    Whitehead, Jennifer; Keller-Peck, Cynthia; Kucera, Jan; Tourtellotte, Warren G

    2005-01-01

    Glial cell-line derived neurotrophic factor (GDNF) is a potent survival factor for motor neurons. Previous studies have shown that some motor neurons depend upon GDNF during development but this GDNF-dependent motor neuron subpopulation has not been characterized. We examined GDNF expression patterns in muscle and the impact of altered GDNF expression on the development of subtypes of motor neurons. In GDNF hemizygous mice, motor neuron innervation to muscle spindle stretch receptors (fusimotor neuron innervation) was decreased, whereas in transgenic mice that overexpress GDNF in muscle, fusimotor innervation to muscle spindles was increased. Facial motor neurons, which do not contain fusimotor neurons, were not changed in number when GDNF was over expressed by facial muscles during their development. Taken together, these data indicate that fusimotor neurons depend upon GDNF for survival during development. Since the fraction of cervical and lumbar motor neurons lost in GDNF-deficient mice at birth closely approximates the size of the fusimotor neuron pool, these data suggest that motor neuron loss in GDNF-deficient mice may be primarily of fusimotor neuron origin.

  14. Immune clearance of attenuated rabies virus results in neuronal survival with altered gene expression.

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    Emily A Gomme

    Full Text Available Rabies virus (RABV is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, to the absence of a permanent "mark" on once-infected cells that allow their identification long after viral clearance. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre to switch neurons constitutively expressing tdTomato (red to expression of a Cre-inducible EGFP (green, permanently marking neurons that had been infected in vivo. We used fluorescence microscopy and quantitative real-time PCR to measure the survival of neurons after viral clearance; we found that the vast majority of RABV-infected neurons survive both infection and immunological clearance. We were able to isolate these previously infected neurons by flow cytometry and assay their gene expression profiles compared to uninfected cells. We observed transcriptional changes in these "cured" neurons, predictive of decreased neurite growth and dysregulated microtubule dynamics. This suggests that viral clearance, though allowing for survival of neurons, may not restore them to their pre-infection functionality. Our data provide a proof-of-principle foundation to re-evaluate the etiology of human central nervous system diseases of unknown etiology: viruses may trigger permanent neuronal

  15. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years

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    Mendez, Ivar; Viñuela, Angel; Astradsson, Arnar

    2008-01-01

    Postmortem analysis of five subjects with Parkinson's disease 9-14 years after transplantation of fetal midbrain cell suspensions revealed surviving grafts that included dopamine and serotonin neurons without pathology. These findings are important for the understanding of the etiopathogenesis...

  16. Agonists of fibroblast growth factor receptor induce neurite outgrowth and survival of cerebellar granule neurons

    DEFF Research Database (Denmark)

    Li, Shizhong; Christensen, Claus; Køhler, Lene B

    2009-01-01

    Fibroblast growth factor receptor (FGFR) signaling is pivotal in the regulation of neurogenesis, neuronal differentiation and survival, and synaptic plasticity both during development and in adulthood. In order to develop low molecular weight agonists of FGFR, seven peptides, termed hexafins...

  17. Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP.

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    Zhang, Dawei; Yang, Shanzheng; Toledo, Enrique M; Gyllborg, Daniel; Saltó, Carmen; Carlos Villaescusa, J; Arenas, Ernest

    2017-08-22

    Parkinson's disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. We found that the extracellular matrix protein laminin-511 (LM511) promoted the survival and differentiation of mDA neurons. LM511 bound to integrin α3β1 and activated the transcriptional cofactor YAP. LM511-YAP signaling enhanced cell survival by inducing the expression of the microRNA miR-130a, which suppressed the synthesis of the cell death-associated protein PTEN. In addition, LM511-YAP signaling increased the expression of transcription factors critical for mDA identity, such as LMX1A and PITX3, and prevented the loss of mDA neurons in response to oxidative stress, a finding that warrants further investigation to assess therapeutic potential for PD patients. We propose that by enhancing LM511-YAP signaling, it may be possible to prevent mDA neuron degeneration in PD or enhance the survival of mDA neurons in cell replacement therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  18. Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy

    NARCIS (Netherlands)

    Cobben, J. M.; van der Steege, G.; Grootscholten, P.; de Visser, M.; Scheffer, H.; Buys, C. H.

    1995-01-01

    DNA studies in 103 spinal muscular atrophy (SMA) patients from The Netherlands revealed homozygosity for a survival motor neuron (SMN) deletion in 96 (93%) of 103. Neuronal apoptosis inhibitory protein deletions were found in 38 (37%) of 103 and occurred most frequently in SMA type I. SMN deletions

  19. Dicer expression is essential for adult midbrain dopaminergic neuron maintenance and survival

    OpenAIRE

    Pang, Xueyan; Hogan, Eric M.; Gao, Guangping; Gardner, Paul D.; Tapper, Andrew R.

    2013-01-01

    The type III RNAse, Dicer, is responsible for the processing of microRNA (miRNA) precursors into functional miRNA molecules, non-coding RNAs that bind to and target messenger RNAs for repression. Dicer expression is essential for mouse midbrain development and dopaminergic (DAergic) neuron maintenance and survival during the early post-natal period. However, the role of Dicer in adult mouse DAergic neuron maintenance and survival is unknown. To bridge this gap in knowledge, we selectively kno...

  20. Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival

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    Pellegrino, Christophe; Gubkina, Olena; Schaefer, Michael; Becq, Hélène; Ludwig, Anastasia; Mukhtarov, Marat; Chudotvorova, Ilona; Corby, Severine; Salyha, Yuriy; Salozhin, Sergey; Bregestovski, Piotr; Medina, Igor

    2011-01-01

    Abstract KCC2 is a neuron-specific potassium–chloride co-transporter controlling intracellular chloride homeostasis in mature and developing neurons. It is implicated in the regulation of neuronal migration, dendrites outgrowth and formation of the excitatory and inhibitory synaptic connections. The function of KCC2 is suppressed under several pathological conditions including neuronal trauma, different types of epilepsies, axotomy of motoneurons, neuronal inflammations and ischaemic insults. However, it remains unclear how down-regulation of the KCC2 contributes to neuronal survival during and after toxic stress. Here we show that in primary hippocampal neuronal cultures the suppression of the KCC2 function using two different shRNAs, dominant-negative KCC2 mutant C568A or DIOA inhibitor, increased the intracellular chloride concentration [Cl−]i and enhanced the toxicity induced by lipofectamine-dependent oxidative stress or activation of the NMDA receptors. The rescuing of the KCC2 activity using over-expression of the active form of the KCC2, but not its non-active mutant Y1087D, effectively restored [Cl−]i and enhanced neuronal resistance to excitotoxicity. The reparative effects of KCC2 were mimicked by over-expression of the KCC3, a homologue transporter. These data suggest an important role of KCC2-dependent potassium/chloride homeostasis under neurototoxic conditions and reveal a novel role of endogenous KCC2 as a neuroprotective molecule. PMID:21486764

  1. The effect of fluorescent nanodiamonds on neuronal survival and morphogenesis

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    Huang, Yung-An; Kao, Chun-Wei; Liu, Kuang-Kai; Huang, Hou-Syun; Chiang, Ming-Han; Soo, Ching-Ren; Chang, Huan-Cheng; Chiu, Tzai-Wen; Chao, Jui-I.; Hwang, Eric

    2014-11-01

    Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic applications. In previous studies, ND has been reported to have outstanding biocompatibility and high uptake rate in various cell types. ND containing nitrogen-vacancy centers exhibit fluorescence property is called fluorescent nanodiamond (FND), and has been applied for bio-labeling agent. However, the influence and application of FND on the nervous system remain elusive. In order to study the compatibility of FND on the nervous system, neurons treated with FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in primary neurons from either central (CNS) or peripheral nervous system (PNS); neither did intracranial injection of FND affect animal behavior. The neuronal uptake of FNDs was confirmed using flow cytometry and confocal microscopy. However, FND caused a concentration-dependent decrease in neurite length in both CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of neurite length was due to the spatial hindrance of FND on advancing axonal growth cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but interfere with neuronal morphogenesis, and should be taken into consideration when applications involve actively growing neurites (e.g. nerve regeneration).

  2. Social change affects the survival of new neurons in the forebrain of adult songbirds.

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    Lipkind, D; Nottebohm, F; Rado, R; Barnea, A

    2002-06-15

    Many new neurons are added to the adult avian brain. Most of them die 3-5 weeks after they are born (Nature (Lond.) 335 (1988) 353; J. Comp. Neurol 411 (1999) 487). Those that survive replace, numerically, older ones that have died (Neuron 25 (2000) 481). It has been suggested that the new neurons enhance the brain's ability to acquire new long-term memories (review in Sci. Am. 260 (1989) 74). If so, perhaps an increase in social complexity affects the survival of new neurons in a social species. To test this hypothesis, we treated adult zebra finches (Taeniopygia guttata) with [3H]-thymidine immediately before introducing them into one of three different social environments that differed in complexity and killed them 40 days later. There was a significant difference between experimental groups in the number of [3H]-labeled neurons in neostriatum caudale (NC), high vocal center (HVC) and Area X, three forebrain regions that are involved in vocal communication. In these regions, birds placed in a large heterosexual group had more new neurons than birds kept singly or as male-female pairs. Regulation of new neuron survival by extent of circuit use may be a general mechanism for ensuring that neuronal replacement is closely attuned to environmental change.

  3. Mineralocorticoid receptor overexpression facilitates differentiation and promotes survival of embryonic stem cell-derived neurons.

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    Munier, Mathilde; Law, Frédéric; Meduri, Geri; Le Menuet, Damien; Lombès, Marc

    2012-03-01

    Mineralocorticoid receptor (MR), highly expressed in the hippocampus, binds corticosteroid hormones and coordinately participates, with the glucocorticoid receptor, to the control of stress responses, memorization, and behavior. To investigate the impact of MR in neuronal survival, we generated murine embryonic stem (ES) cells that overexpress human MR (hMR) (P1-hMR) and are induced to differentiate into mature neurons. We showed that recombinant MR expression increased throughout differentiation and is 2-fold higher in P1-hMR ES-derived neurons compared with wild-type controls, whereas glucocorticoid receptor expression was unaffected. Although proliferation and early neuronal differentiation were comparable in P1-hMR and wild-type ES cells, MR overexpression was associated with higher late neuronal marker expression (microtubule-associated protein 2 and β-tubulin III). This was accompanied by a shift towards neuron survival with an increased ratio of anti- vs. proapoptotic molecules and 50% decreased caspase 3 activity. Knocking down MR overexpression by small interfering RNA drastically reversed neuroprotective effects with reduced Bcl(2)/Bax ratio and decreased microtubule-associated protein 2 expression. P1-hMR neurons were protected against oxidative stress-induced apoptosis through reduced caspase 3 activation and drastically increased Bcl(2)/Bax ratio and β-tubulin III expression. We demonstrated the involvement of MR in neuronal differentiation and survival and identify MR as an important neuroprotective mediator opening potential pharmacological strategies.

  4. Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation.

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    Huang, Xinghua; Chen, Mo; Ding, Yan; Wang, Qin

    2017-03-01

    Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo. © 2017 Wiley Periodicals, Inc.

  5. Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux.

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    Zhang, Mengting; Tao, Wufan; Yuan, Zengqiang; Liu, Yaobo

    2017-10-01

    The mammalian Ste20-like kinase 1 (Mst-1) is a serine-threonine kinase and a component of the Hippo tumor suppressor pathway, which reacts to pathologically relevant stress and regulates cell death. However, little is known about its role in spinal cord injury. Here, we found that p-Mst-1, the activated form of Mst-1, was induced in the post-traumatic spinal motor neurons. In vivo evidence demonstrated that Mst-1 deficiency promoted post-traumatic spinal motor neuron survival, Basso mouse scale scores, and synapse survival. Moreover, we found that autophagosome formation and autolysosome degradation enhanced by Mst-1 deficiency were crucial to attenuate the death of injured spinal motor neurons. Taken together, our findings demonstrate that Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux. © 2017 International Society for Neurochemistry.

  6. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  7. Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state.

    Directory of Open Access Journals (Sweden)

    C Devin Brisson

    Full Text Available Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a 'persistent vegetative state' where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by 'higher' hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT imaging in response to 10 minutes of oxygen/glucose deprivation (OGD revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1-10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival

  8. Schwann cell-derived factors support serotoninergic neuron survival and promote neurite outgrowth

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    R Pellitteri

    2009-12-01

    Full Text Available During embryogenesis and the postnatal period, neurons and glia interact in the development and differentiation of specific populations of nerve cells. Both in the peripheral (PNS and in the central nervous system (CNS, glial cells have been shown in various experimental conditions to constitute a favorable substrate for neural adhesion, neural polarity, shape and axonal extension, while numerous soluble molecules secreted by neurons influence the survival and differentiation of the glial cells themselves. The aim of the present work was to investigate the influence of postnatal Schwann cells (SC on embryonic serotoninergic (5-HT neurons of the raphe, in order to study the possible influence of the peripheral glia on the CNS neurons. Cultures of SC from sciatic nerve of postnatal rats and neurons from rat embryonic rhombencephalon were successfully established and cells were immunocytochemically characterized. The number of 5-HT neurons, and the number and length of their branches were quantified in the cultures of 5-HT neurons, in cultures added with Nerve Growth Factor (NGF and Insulin-like Growth Factor I (IGF-I, in co-cultures with SC and in cultures added with conditioned medium obtained from SC cultures. The results indicated that SC have the capacity to promote the survival and growth of 5-HT neurons in culture, and that this activity is mediated by soluble factors. Although the precise nature and mechanism of action of the growth factor or factors produced by SC in the presence of 5-HT neurons was not identified, our results add more data on the possible activity of the peripheral glia in promoting and enhancing the survival and outgrowth of the CNS neurons.

  9. Trophic factors as modulators of motor neuron physiology and survival: implications for ALS therapy

    Directory of Open Access Journals (Sweden)

    Luis B Tovar-y-Romo

    2014-02-01

    Full Text Available Motor neuron physiology and development depend on a continuous and tightly regulated trophic support from a variety of cellular sources. Trophic factors guide the generation and positioning of motor neurons during every stage of the developmental process. As well, they are involved in axon guidance and synapse formation. Even in the adult spinal cord an uninterrupted trophic input is required to maintain neuronal functioning and protection from noxious stimuli. Among the trophic factors that have been demonstrated to participate in motor neuron physiology are vascular endothelial growth factor (VEGF, glial-derived neurotrophic factor (GDNF, ciliary neurotrophic factor (CNTF and insulin-like growth factor 1 (IGF-1. Upon binding to membrane receptors expressed in motor neurons or neighboring glia, these trophic factors activate intracellular signaling pathways that promote cell survival and have protective action on motor neurons, in both in vivo and in vitro models of neuronal degeneration. For these reasons these factors have been considered a promising therapeutic method for amyotrophic lateral sclerosis (ALS and other neurodegenerative diseases, although their efficacy in human clinical trials have not yet shown the expected protection. In this review we summarize experimental data on the role of these trophic factors in motor neuron function and survival, as well as their mechanisms of action. We also briefly discuss the potential therapeutic use of the trophic factors and why these therapies may have not been yet successful in the clinical use.

  10. Edited GluR2, a gatekeeper for motor neurone survival?

    Science.gov (United States)

    Buckingham, S D; Kwak, S; Jones, A K; Blackshaw, S E; Sattelle, D B

    2008-11-01

    Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder of motor neurones. Although the genetic basis of familial forms of ALS has been well explored, the molecular basis of sporadic ALS is less well understood. Recent evidence has linked sporadic ALS with the failure to edit key residues in ionotropic glutamate receptors, resulting in excessive influx of calcium ions into motor neurones which in turn triggers cell death. Here we suggest that edited AMPA glutamate (GluR2) receptor subunits serve as gatekeepers for motor neurone survival.

  11. Oestrogen receptors enhance dopamine neurone survival in rat midbrain.

    Science.gov (United States)

    Johnson, M L; Ho, C C; Day, A E; Walker, Q D; Francis, R; Kuhn, C M

    2010-04-01

    Previous findings in our laboratory and elsewhere have shown that ovariectomy of rats in adulthood attenuates cocaine-stimulated locomotor behaviour. Ovarian hormones enhance both cocaine-stimulated behaviour and increase dopamine overflow after psychomotor stimulants. The present study aimed to determine whether ovarian hormones have these effects in part by maintaining dopamine neurone number in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) and to investigate the roles of specific oestrogen receptors (ERs) in the maintenance of mesencephalic dopamine neurones. To accomplish this goal, we used unbiased stereological techniques to estimate the number of tyrosine hydroxylase-immunoreactive (TH-IR) cell bodies in midbrain regions of intact, ovariectomised and hormone-replaced female rats and mice. Animals received active or sham gonadectomy on postnatal day 60 and received vehicle, 17beta-oestradiol (E(2)) or selective ER agonists propyl-pyrazole-triol (PPT, ERalpha) or diarylpropionitrile (DPN, ERbeta) for 1 month post-surgery. In both rats and mice, ovariectomy reduced the number of TH-IR cells in the SNpc and VTA. Replacement with E(2), PPT or DPN prevented or attenuated the loss observed with ovariectomy in both rats and mice. An additional study using ER knockout mice revealed that adult female mice lacking ERalpha had fewer TH-IR cells in midbrain regions than wild-type mice, whereas mice lacking ERbeta had TH-IR cell counts comparable to wild-type. These findings suggest that, although both ER subtypes play a role in the maintenance of TH-IR cell number in the SNpc and VTA, ERalpha may play a more significant role.

  12. Androgen decreases dopamine neurone survival in rat midbrain.

    Science.gov (United States)

    Johnson, M L; Day, A E; Ho, C C; Walker, Q D; Francis, R; Kuhn, C M

    2010-04-01

    Clinical studies show that men are more likely to develop disorders affecting midbrain dopaminergic pathways, such as drug addiction and Parkinson's disease (PD). Although a great deal of focus has been given to the role of oestrogen in the maintenance of midbrain dopaminergic pathways, little is known about how testosterone influences these pathways. In the present study, we used stereological analysis of tyrosine hydroxylase-immunoreactive (TH-IR) cell bodies to determine how testosterone influences the dopaminergic cell bodies of the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Rats and mice were castrated at postnatal day (PN) 60, and these midbrain cell populations were counted on PN 90. One month after castration, TH-IR cell number had increased in the SNpc and VTA of rats and mice. Replacement with testosterone or the non-aromatisable analogue dihydrotestosterone (DHT) in castrated animals reduced TH-IR cell number in the SNpc and VTA in rats. In mice, the decrease of TH-IR cell number with testosterone or DHT replacement was observed only in the SNpc. The apparent increase in TH-IR neurone number after castration is not explained by an increase in TH expression because the number of nondopaminergic cells (TH-immunonegative, TH-IN) did not decrease proportionally after castration. TH-IN cell number did not change after castration or hormone replacement in rat or mouse SNpc or VTA. These findings suggest that testosterone may play a suppressive role in midbrain dopaminergic pathways.

  13. Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Liu, Kevin X; Edwards, Benjamin; Lee, Sheena; Finelli, Mattéa J; Davies, Ben; Davies, Kay E; Oliver, Peter L

    2015-05-01

    Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder characterized by the progressive loss of spinal motor neurons. While the aetiological mechanisms underlying the disease remain poorly understood, oxidative stress is a central component of amyotrophic lateral sclerosis and contributes to motor neuron injury. Recently, oxidation resistance 1 (OXR1) has emerged as a critical regulator of neuronal survival in response to oxidative stress, and is upregulated in the spinal cord of patients with amyotrophic lateral sclerosis. Here, we tested the hypothesis that OXR1 is a key neuroprotective factor during amyotrophic lateral sclerosis pathogenesis by crossing a new transgenic mouse line that overexpresses OXR1 in neurons with the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Interestingly, we report that overexpression of OXR1 significantly extends survival, improves motor deficits, and delays pathology in the spinal cord and in muscles of SOD1(G93A) mice. Furthermore, we find that overexpression of OXR1 in neurons significantly delays non-cell-autonomous neuroinflammatory response, classic complement system activation, and STAT3 activation through transcriptomic analysis of spinal cords of SOD1(G93A) mice. Taken together, these data identify OXR1 as the first neuron-specific antioxidant modulator of pathogenesis and disease progression in SOD1-mediated amyotrophic lateral sclerosis, and suggest that OXR1 may serve as a novel target for future therapeutic strategies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  14. Congenital cytoplasmic body myopathy with survival motor neuron gene deletion or Werdnig-Hoffmann disease

    DEFF Research Database (Denmark)

    Vajsar, J; Balslev, T; Ray, P N

    1998-01-01

    bodies. However, molecular analysis revealed a homozygous deletion of exons 7 and 8 of the survival motor neuron (SMN) gene, suggesting that the patient had Werdnig-Hoffmann disease. We recommend that every patient with congenital cytoplasmic body myopathy be tested for SMN gene deletion....

  15. Factors that Contribute to Neuron Survival and Neuron Growth after Injury

    Science.gov (United States)

    1993-02-03

    Feringa et aL, 1987). In many neural systems cell death after axotomy in neonates exceeds that which follows the same injury in adults (Prendergast and... Feringa ER, Pruitt JN, McBride RL, Vahising HL (1987) Changes in number and size of Clarke’s column neurons after cord transection. J. Neuropath...the generation and degeneration of hippocampal neuroarchitecture. J. Neurosci. 93728-3740. McBride RL, Feringa ER, Smith BE (1988) The fate of

  16. Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

    DEFF Research Database (Denmark)

    Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

    2017-01-01

    of the previous work aiming to test the hypothesis that rats subjected to ECS in combination with chronic restraint stress (CRS) display increased formation of new hippocampal neurons, which have a potential for long-term survival. Furthermore, using mediation analysis, we tested if an ECS-induced increase......U-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found...... that, while ECS increases neurogenesis, this formation of new neurons was not associated to ameliorated immobility in the FST. This implies that other ECS-induced effects than neurogenesis must be part of mediating the antidepressant action of ECS. Taken together, the results of the present study...

  17. Onset and spreading patterns of lower motor neuron involvements predict survival in sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Fujimura-Kiyono, Chieko; Kimura, Fumiharu; Ishida, Simon; Nakajima, Hideto; Hosokawa, Takafumi; Sugino, Masakazu; Hanafusa, Toshiaki

    2011-11-01

    To define patterns of spread through the order of lower motor neuron involvement (first, second or third order), relationships between interval or sites of affected areas from onset to involvement of a second region, and prognosis, including 5 year survival, normal preservation of motor function at onset of respiratory symptoms and cumulative occurrence of each region and direction of spread. 150 patients with sporadic amyotrophic lateral sclerosis (ALS) underwent follow-up at 3 month intervals until the appearance of respiratory symptoms. Symptom appearances were determined using the revised version of the ALS Functional Rating Scale. Median survival with combined type onset (two regions simultaneously) was shorter (18 months) than with bulbar onset (26 months, p=0.01). The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. 5 year survival rate was 21% for lower limb onset, 18% for upper limb onset and 16% for bulbar onset. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Early manifestations of bulbar symptoms within 1 year were associated with worse survival (pspread longitudinally to adjacent regions. Bulbar function remained preserved in 27%, lower limb function in 10% and upper limb function in 2.7%. The interval between onset and involvement of the second region is an important predictor of survival. The data support the contiguous anatomical propagation of lower motor neuron involvement in sporadic ALS.

  18. Targeted assessment of lower motor neuron burden is associated with survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Devine, Matthew S; Ballard, Emma; O'Rourke, Peter; Kiernan, Matthew C; Mccombe, Pamela A; Henderson, Robert D

    2016-01-01

    Estimating survival in amyotrophic lateral sclerosis (ALS) is challenging due to heterogeneity in clinical features of disease and a lack of suitable markers that predict survival. Our aim was to determine whether scoring of upper or lower motor neuron weakness is associated with survival. With this objective, 161 ALS subjects were recruited from two tertiary referral centres. Scoring of upper (UMN) and lower motor neuron (LMN) signs was performed, in addition to a brief questionnaire. Subjects were then followed until the censorship date. Univariate analysis was performed to identify variables associated with survival to either non-invasive ventilation (NIV) or death, which were then further characterized using Cox regression. Results showed that factors associated with reduced survival included older age, bulbar and respiratory involvement and shorter diagnostic delay (all p score was strongly associated with time to NIV or death (p ≤0.001) whereas UMN scores were poorly associated with survival. In conclusion, our results suggest that, early in disease assessment and in the context of other factors (age, bulbar, respiratory status), the burden of LMN weakness provides an accurate estimate of outcome. Such a scoring system could predict prognosis, and thereby aid in selection of patients for clinical trials.

  19. Survival of hippocampal and cortical neurons in a mixture of MEM+ and B27-supplemented neurobasal medium.

    Science.gov (United States)

    Xie, C; Markesbery, W R; Lovell, M A

    2000-03-01

    Serum-free B-27 supplemented neurobasal (NB) and a 10% fetal bovine serum-supplemented Eagle's minimum essential medium (MEM+) are used to culture rat embryonic hippocampal neurons for different purposes. Although NB medium leads to enhanced cell survival, it contains biological antioxidants and is not suitable for the study of free radical damage and oxidation in cultured neurons. MEM+ without additional antioxidants has been used widely in the study of free radical damage and oxidation, although it does not support optimum neuronal survival in culture. Serum in MEM+ leads to enhanced cell survival but also promotes glial cell proliferation. In this study, we used a new combination medium (NM-2) that consists of both NB and MEM+ for growing primary hippocampal and cortical neuronal cultures. NM-2 enhanced neuronal survival 78.9% for dissociated neurons at a density of 50 cells/mm(2) and 83.1% for 100 cells/mm(2), while decreasing glial cell proliferation to 2-3% and completely inhibiting oligodendrocytes. The NM-2 minimized the effectiveness of antioxidants in the medium to the neurotoxin 4-hydroxynonenal. It also decreased neuronal clumping and provided a more even distribution of neurons. Neurons survived for 4 weeks in NM-2 without changing the original medium. NM-2 provides a good environment for studies of free radical damage and oxidation of neurons. The combination incorporates the best of both NB and MEM+ that results in high neuron survival rate, low glial cell proliferation, reduced antioxidant level, and provides relatively pure cultures of hippocampal and cortical neurons.

  20. Neurotrophins in the ear: their roles in sensory neuron survival and fiber guidance.

    Science.gov (United States)

    Fritzsch, Bernd; Tessarollo, Lino; Coppola, Enzo; Reichardt, Louis F

    2004-01-01

    We review the history of neurotrophins in the ear and the current understanding of the function of neurotrophins in ear innervation, development and maintenance. Only two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), and their receptors, tyrosine kinase B (TrkB) and TrkC, appear to provide trophic support for inner ear sensory neuron afferents. Mice lacking either both receptors or both ligands lose essentially all sensory innervation of targets in the vestibular and auditory systems of the ear. Analyzes of single mutants show less complete and differential effects on innervation of the different sensory organs within the ear. BDNF and TrkB are most important for survival of vestibular sensory neurons whereas NT-3 and TrkC are most important for survival of cochlear sensory neurons. The largely complementary roles of BDNF to TrkB and NT-3 to TrkC signaling do not reflect specific requirements for innervation of different classes of hair cells. Most neurons express both receptors. Instead, the losses observed in single mutants are related to the spatio-temporal expression pattern of the two neurotrophins. In an area where only one neurotrophin is expressed at a particular time in development, the other neurotrophin is not present to compensate for this absence, resulting in death of neurons innervating that region. Decisive evidence for this suggestion is provided by transgenic mice in which the BDNF coding region has been inserted into the NT-3 gene, resulting in expression of BDNF instead of NT-3. The expression of BDNF in the spatio-temporal pattern of NT-3 results in survival of almost all neurons that are normally lost in the NT-3 mutant. Thus, BDNF and NT-3 have a high level of functional equivalence for inner ear sensory neuron survival. Further analysis of the patterns of afferent fiber losses in mutations that do not develop differentiated hair cells shows that the expression of neurotrophins is remarkably strong and can

  1. Oxidative DNA Damage in Neurons: Implication of Ku in Neuronal Homeostasis and Survival

    Directory of Open Access Journals (Sweden)

    Daniela De Zio

    2012-01-01

    Full Text Available Oxidative DNA damage is produced by reactive oxygen species (ROS which are generated by exogenous and endogenous sources and continuously challenge the cell. One of the most severe DNA lesions is the double-strand break (DSB, which is mainly repaired by nonhomologous end joining (NHEJ pathway in mammals. NHEJ directly joins the broken ends, without using the homologous template. Ku70/86 heterodimer, also known as Ku, is the first component of NHEJ as it directly binds DNA and recruits other NHEJ factors to promote the repair of the broken ends. Neurons are particularly metabolically active, displaying high rates of transcription and translation, which are associated with high metabolic and mitochondrial activity as well as oxygen consumption. In such a way, excessive oxygen radicals can be generated and constantly attack DNA, thereby producing several lesions. This condition, together with defective DNA repair systems, can lead to a high accumulation of DNA damage resulting in neurodegenerative processes and defects in neurodevelopment. In light of recent findings, in this paper, we will discuss the possible implication of Ku in neurodevelopment and in mediating the DNA repair dysfunction observed in certain neurodegenerations.

  2. APP regulates NGF receptor trafficking and NGF-mediated neuronal differentiation and survival.

    Directory of Open Access Journals (Sweden)

    Yun-wu Zhang

    Full Text Available β-Amyloid precursor protein (APP is a key factor in Alzheimer's disease (AD but its physiological function is largely undetermined. APP has been found to regulate retrograde transport of nerve growth factor (NGF, which plays a crucial role in mediating neuronal survival and differentiation. Herein, we reveal the mechanism underlying APP-mediated NGF trafficking, by demonstrating a direct interaction between APP and the two NGF receptors, TrkA and p75NTR. Downregulation of APP leads to reduced cell surface levels of TrkA/p75NTR and increased endocytosis of TrkA/p75NTR and NGF. In addition, APP-deficient cells manifest defects in neurite outgrowth and are more susceptible to Aβ-induced neuronal death at physiological levels of NGF. However, APP-deficient cells show better responses to NGF-stimulated differentiation and survival than control cells. This may be attributed to increased receptor endocytosis and enhanced activation of Akt and MAPK upon NGF stimulation in APP-deficient cells. Together, our results suggest that APP mediates endocytosis of NGF receptors through direct interaction, thereby regulating endocytosis of NGF and NGF-induced downstream signaling pathways for neuronal survival and differentiation.

  3. Survival, differentiation, and connectivity of ventral mesencephalic dopamine neurons following transplantation.

    Science.gov (United States)

    Thompson, Lachlan; Björklund, Anders

    2012-01-01

    The reconstruction of midbrain dopamine (DA) circuitry through intracerebral transplantation of new DA neurons contained in embryonic ventral mesencephalon (VM) is a promising therapeutic approach for Parkinson's disease (PD). Although some of the early open-label trials have provided proof-of-principal that VM grafts can provide sustained improvement of motor function in some patients, subsequent trials showed that the functional response can be highly variable. This chapter reviews an extensive body of basic and clinical research on the survival, differentiation, and connectivity of DA neurons in VM grafts, and also looks at how these parameters are affected by certain host- and donor-specific variables. We also review how technical advances in the tools available to study the integration of grafted DA neurons, such as transgenic reporter mice, have made significant contributions to our understanding of the capacity of different DA neuronal subtypes for target-directed growth and innervation of appropriate host brain structures. Our established and on-going understanding of the capacity of grafted DA neurons to structurally and functionally integrate following transplantation forms an important basis for the refinement and optimization of VM grafting procedures, and also the development of new procedures based on the use of stem cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials.

    Science.gov (United States)

    Hannan, Md Abdul; Kang, Ji-Young; Mohibbullah, Md; Hong, Yong-Ki; Lee, Hyunsook; Choi, Jae-Suk; Choi, In Soon; Moon, Il Soo

    2014-02-27

    Moringa oleifera Lam. (Moringaceae) by virtue of its high nutritional as well as ethnomedical values has been gaining profound interest both in nutrition and medicinal research. The leaf of this plant is used in ayurvedic medicine to treat paralysis, nervous debility and other nerve disorders. In addition, research evidence also suggests the nootropic as well as neuroprotective roles of Moringa oleifera leaf in animal models. The aim of the present study was to evaluate the effect of Moringa oleifera leaf in the primary hippocampal neurons regarding its neurotrophic and neuroprotective properties. The primary culture of embryonic hippocampal neurons was incubated with the ethanol extract of Moringa oleifera leaf (MOE). After an indicated time, cultures were either stained directly with a lipophilic dye, DiO, or fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for neurite maturation and synaptogenesis were performed using Image J software. Neuronal viability was evaluated using trypan blue exclusion and lactate dehydrogenase assays. MOE promoted neurite outgrowth in a concentration-dependent manner with an optimal concentration of 30 μg/mL. As a very initial effect, MOE significantly promoted the earlier stages of neuronal differentiation. Subsequently, MOE significantly increased the number and length of dendrites, the length of axon, and the number and length of both dendrite and axonal branches, and eventually facilitated synaptogenesis. The β-carotene, one major compound of MOE, promoted neuritogensis, but the increase was not comparable with the effect of MOE. In addition, MOE supported neuronal survival by protecting neurons from naturally occurring cell death in vitro. Our findings indicate that MOE promotes axodendritic maturation as well as provides neuroprotection suggesting a promising pharmacological importance of this nutritionally and ethnomedically important plant for the well-being of nervous system. Copyright

  5. Peptides modeled after the alpha-domain of metallothionein induce neurite outgrowth and promote survival of cerebellar granule neurons

    DEFF Research Database (Denmark)

    Asmussen, Johanne Wirenfeldt; Ambjørn, Malene; Bock, Elisabeth

    2009-01-01

    Metallothionein (MT) is a metal-binding protein capable of preventing oxidative stress and apoptotic cell death in the central nervous system of mammals, and hence is of putative therapeutic value in the treatment of neurodegenerative disorders. Recently, we demonstrated that a peptide modeled...... after the beta-domain of MT, EmtinB, induced neurite outgrowth and increased neuronal survival through binding to receptors of the low-density lipoprotein receptor family (LDLR). The present study identified two MT alpha-domain-derived peptide sequences termed EmtinAn and EmtinAc, each consisting of 14...... amino acids, as potent stimulators of neuronal differentiation and survival of primary neurons. In addition, we show that a peptide derived from the N-terminus of the MT beta-domain, EmtinBn, promotes neuronal survival. The neuritogenic and survival promoting effects of EmtinAc, similar to MT and Emtin...

  6. DELETIONS OF THE SURVIVAL MOTOR-NEURON GENE IN UNAFFECTED SIBLINGS OF PATIENTS WITH SPINAL MUSCULAR-ATROPHY

    NARCIS (Netherlands)

    COBBEN, JM; VANDERSTEEGE, G; GROOTSCHOLTEN, P; DEVISSER, M; SCHEFFER, H; BUYS, CHCM

    1995-01-01

    DNA studies in 103 spinal muscular atrophy (SMA) patients from The Netherlands revealed homozygosity for a survival motor neuron (SMN) deletion in 96 (93%) of 103. Neuronal apoptosis inhibitory protein deletions were found in 38 (37%) of 103 and occurred most frequently in SMA type I. SMN deletions

  7. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of); Jang, Deok-Jin [Department of Applied Biology, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711 (Korea, Republic of); Lee, Jin-A, E-mail: leeja@hnu.kr [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of)

    2013-08-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.

  8. PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival

    Directory of Open Access Journals (Sweden)

    Yunjong Lee

    2017-01-01

    Full Text Available Mutations in PTEN-induced putative kinase 1 (PINK1 and parkin cause autosomal-recessive Parkinson’s disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746 that plays an important role in dopamine cell loss through repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α promoter activity. Here, we show that PARIS links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival. PINK1 interacts with and phosphorylates serines 322 and 613 of PARIS to control its ubiquitination and clearance by parkin. PINK1 phosphorylation of PARIS alleviates PARIS toxicity, as well as repression of PGC-1α promoter activity. Conditional knockdown of PINK1 in adult mouse brains leads to a progressive loss of dopaminergic neurons in the substantia nigra that is dependent on PARIS. Altogether, these results uncover a function of PINK1 to direct parkin-PARIS-regulated PGC-1α expression and dopaminergic neuronal survival.

  9. Large-Scale Production of Adeno-Associated Viral Vector Serotype-9 Carrying the Human Survival Motor Neuron Gene.

    Science.gov (United States)

    Rashnonejad, Afrooz; Chermahini, Gholamhossein Amini; Li, Shaoyong; Ozkinay, Ferda; Gao, Guangping

    2016-01-01

    Recombinant AAV (rAAV) vectors are a suitable vector for gene therapy studies because of desired characteristics such as low immunogenicity, transfection of non-dividing and dividing cells, and long-term expression of the transgene. In this study, the large-scale production of single stranded (ss) and self-complementary (sc) AAV9 carrying the human survival motor neuron (SMN) gene (AAV9-SMN) suitable for in vivo gene therapy studies of SMA was described. SMN cDNA has been cloned into pAAV-CB6-PI and pAAVsc-CB6-PI with and without its specific UTRs, respectively. Both plasmids bear CMV enhancer/beta-actin (CB) promoter, CMV IE enhancer, and polyadenylation signal sequences. 2.5 μg of constructed pAAV-CB6-PI-SMN and pAAVsc-CB6-PI-SMN cause to, respectively, 4.853- and 2.321-fold increases in SMN protein levels in transfected cells compared to untransfected cells. Ss and scAAV9-SMN vectors were also produced from these plasmids by transient transfection of HEK293 cells using CaCl2 solution. The silver staining and electron microscopy analysis demonstrated good quality of both isolated vectors, ssAAV9-SMN and scAAV9-SMN, with the titers of 2.00E+13 and 1.00E+13 GC/ml. The results of this study show that, the plasmid containing UTR elements causes to twice more SMN gene expression in transfected cells. The quality control results show that both produced ss and scAAV9-SMN are suitable for in vivo studies.

  10. Cyclic AMP promotes axon regeneration, lesion repair and neuronal survival in lampreys after spinal cord injury.

    Science.gov (United States)

    Lau, Billy Y B; Fogerson, Stephanie M; Walsh, Rylie B; Morgan, Jennifer R

    2013-12-01

    Axon regeneration after spinal cord injury in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Increasing the levels of the second messenger cyclic adenosine monophosphate (cAMP) after spinal cord injury enhances axon regeneration across a wide variety of species, making it an excellent candidate molecule that has therapeutic potential. However, several important aspects of the cellular and molecular mechanisms by which cAMP enhances axon regeneration are still unclear, such as how cAMP affects axon growth patterns, the molecular components within growing axon tips, the lesion scar, and neuronal survival. To address these points, we took advantage of the large, identified reticulospinal (RS) neurons in lamprey, a vertebrate that exhibits robust axon regeneration after a complete spinal cord transection. Application of a cAMP analog, db-cAMP, at the time of spinal cord transection increased the number of axons that regenerated across the lesion site. Db-cAMP also promoted axons to regenerate in straighter paths, prevented abnormal axonal growth patterns, increased the levels of synaptotagmin within axon tips, and increased the number of axotomized neurons that survived after spinal cord injury, thereby increasing the pool of neurons available for regeneration. There was also a transient increase in the number of microglia/macrophages and improved repair of the lesion site. Taken together, these data reveal several new features of the cellular and molecular mechanisms underlying cAMP-mediated enhancement of axon regeneration, further emphasizing the positive roles for this conserved pathway. © 2013.

  11. Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

    Science.gov (United States)

    Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

    2013-01-01

    Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

  12. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena

    2008-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo) has - besides of its well known...... with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...... expression in brain tissue was measured by real time PCR. RESULTS: Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect...

  13. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models

    Science.gov (United States)

    Barmada, Sami J.; Serio, Andrea; Arjun, Arpana; Bilican, Bilada; Daub, Aaron; Ando, D. Michael; Tsvetkov, Andrey; Pleiss, Michael; Li, Xingli; Peisach, Daniel; Shaw, Christopher; Chandran, Siddharthan; Finkbeiner, Steven

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology—cytoplasmic inclusions rich in TDP43. Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause disease even if TDP43 lacks a mutation. Here we showed that individual neurons vary in their ability to clear TDP43 and are exquisitely sensitive to TDP43 levels. To measure TDP43 clearance, we developed and validated a single-cell optical method that overcomes the confounding effects of aggregation and toxicity, and discovered that pathogenic mutations significantly shorten TDP43 half-life. Novel compounds that stimulate autophagy improved TDP43 clearance and localization, and enhanced survival in primary murine neurons and in human stem cell–derived neurons and astrocytes harboring mutant TDP43. These findings indicate that the levels and localization of TDP43 critically determine neurotoxicity and show that autophagy induction mitigates neurodegeneration by acting directly on TDP43 clearance. PMID:24974230

  14. IMPACTS OF TISSUE-TYPE PLASMINOGEN ACTIVATOR (TPA ON NEURONAL SURVIVAL

    Directory of Open Access Journals (Sweden)

    Arnaud eChevilley

    2015-10-01

    Full Text Available Tissue-type plasminogen activator (tPA a serine protease is constituted of five functional domains through which it interacts with different substrates, binding proteins and receptors. In the last years, great interest has been given to the clinical relevance of targeting tPA in different diseases of the central nervous system, in particular stroke. Among its reported functions in the central nervous system, tPA displays both neurotrophic and neurotoxic effects. How can the protease mediate such opposite functions remain unclear but several hypotheses have been proposed. These include an influence of the degree of maturity and/or the type of neurons, of the level of tPA, of its origin (endogenous or exogenous or of its form (single chain tPA versus two chain tPA. In this review, we will provide a synthetic snapshot of our current knowledge regarding the natural history of tPA and discuss how it sustains its pleiotropic functions with focus on excitotoxic/ischemic neuronal death and neuronal survival.

  15. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    Science.gov (United States)

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. In vivo analysis of MEF2 transcription factors in synapse regulation and neuronal survival.

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    M Waseem Akhtar

    Full Text Available MEF2 (A-D transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer collateral pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for MEF2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/dTKO. Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the MEF2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that MEF2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of MEF2C isoform in the brain and suggest that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function.

  17. Type I vs type II spiral ganglion neurons exhibit differential survival and neuritogenesis during cochlear development

    Directory of Open Access Journals (Sweden)

    Housley Gary D

    2011-10-01

    Full Text Available Abstract Background The mechanisms that consolidate neural circuitry are a major focus of neuroscience. In the mammalian cochlea, the refinement of spiral ganglion neuron (SGN innervation to the inner hair cells (by type I SGNs and the outer hair cells (by type II SGNs is accompanied by a 25% loss of SGNs. Results We investigated the segregation of neuronal loss in the mouse cochlea using β-tubulin and peripherin antisera to immunolabel all SGNs and selectively type II SGNs, respectively, and discovered that it is the type II SGN population that is predominately lost within the first postnatal week. Developmental neuronal loss has been attributed to the decline in neurotrophin expression by the target hair cells during this period, so we next examined survival of SGN sub-populations using tissue culture of the mid apex-mid turn region of neonatal mouse cochleae. In organotypic culture for 48 hours from postnatal day 1, endogenous trophic support from the organ of Corti proved sufficient to maintain all type II SGNs; however, a large proportion of type I SGNs were lost. Culture of the spiral ganglion as an explant, with removal of the organ of Corti, led to loss of the majority of both SGN sub-types. Brain-derived neurotrophic factor (BDNF added as a supplement to the media rescued a significant proportion of the SGNs, particularly the type II SGNs, which also showed increased neuritogenesis. The known decline in BDNF production by the rodent sensory epithelium after birth is therefore a likely mediator of type II neuron apoptosis. Conclusion Our study thus indicates that BDNF supply from the organ of Corti supports consolidation of type II innervation in the neonatal mouse cochlea. In contrast, type I SGNs likely rely on additional sources for trophic support.

  18. Effects of silver nanoparticles on survival, biomass change and avoidance behaviour of the endogeic earthworm Allolobophora chlorotica.

    Science.gov (United States)

    Brami, C; Glover, A R; Butt, K R; Lowe, C N

    2017-07-01

    Increasing commercial application of silver nanoparticles (Ag NP) and subsequent presence in wastewater and sewage sludge has raised concerns regarding their effects in the aquatic and terrestrial environment. Several studies have employed standardised acute and chronic earthworm-based tests to establish the toxicological effects of Ag NP within soil. These studies have relied heavily on the use of epigiec earthworm species which may have limited ecological relevance in mineral soil. This study assessed the influence of Ag NP (uncoated 80nm powder) and AgNO3 on survival, change in biomass and avoidance behaviour in a soil dwelling (endogiec) species, Allolobophora chlorotica. Earthworms were exposed for 14 days to soils spiked with Ag NP or AgNO3 at 0, 12.5, 25, 50 and 100mgkg-1 either separately for survival and biomass measurement, or combined within a linear gradient to assess avoidance. Avoidance behaviour was shown to provide the most sensitive endpoint with an observable effect at an Ag NP/AgNO3 concentration of 12.5mgkg-1 compared with 50mgkg-1 for biomass change and 100mgkg-1 for survival. Greater mortality was observed in AgNO3 (66.7%) compared with Ag NP-spiked soils (12.5%) at 100mgkg-1, attributed to increased presence of silver ions. Although comparison of results with studies employing Eisenia fetida and Eisenia andrei suggest that the A. chlorotica response to Ag NP is more sensitive, further research employing both epigeic and endogeic earthworms under similar experimental conditions is required to confirm this observation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Orthodenticle is necessary for survival of a cluster of clonally related dopaminergic neurons in the Drosophila larval and adult brain

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    Pandey Rahul

    2011-10-01

    Full Text Available Abstract Background The dopaminergic (DA neurons present in the central brain of the Drosophila larva are spatially arranged in stereotyped groups that define clusters of bilaterally symmetrical neurons. These clusters have been classified according to anatomical criteria (position of the cell bodies within the cortex and/or projection pattern of the axonal tracts. However, information pertaining to the developmental biology, such as lineage relationship of clustered DA neurons and differential cell subtype-specific molecular markers and mechanisms of differentiation and/or survival, is currently not available. Results Using MARCM and twin-spot MARCM techniques together with anti-tyrosine hydroxylase immunoreactivity, we have analyzed the larval central brain DA neurons from a developmental point of view and determined their time of birth, their maturation into a DA neurotransmitter phenotype as well as their lineage relationships. In addition, we have found that the homeodomain containing transcription factor Orthodenticle (Otd is present in a cluster of clonally related DA neurons in both the larval and adult brain. Taking advantage of the otd hypomorphic mutation ocelliless (oc and the oc2-Gal4 reporter line, we have studied the involvement of orthodenticle (otd in the survival and/or cell fate specification of these post-mitotic neurons. Conclusions Our findings provide evidence of the presence of seven neuroblast lineages responsible for the generation of the larval central brain DA neurons during embryogenesis. otd is expressed in a defined group of clonally related DA neurons from first instar larvae to adulthood, making it possible to establish an identity relationship between the larval DL2a and the adult PPL2 DA clusters. This poses otd as a lineage-specific and differential marker of a subset of clonally related DA neurons. Finally, we show that otd is required in those DA neurons for their survival.

  20. High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation

    Directory of Open Access Journals (Sweden)

    Anne-Lieke F. van Deijk

    2017-08-01

    Full Text Available Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis –docosahexaenoic acid (DHA, uridine and choline– has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro. A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC, improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium, on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

  1. Purified mouse dopamine neurons thrive and function after transplantation into brain but require novel glial factors for survival in culture

    OpenAIRE

    Donaldson, A.E.; Marshall, C.E.; Yang, Ming; Suon, S.; Iacovitti, Lorraine

    2005-01-01

    Cell replacement therapy in Parkinson's disease depends on a reliable source of purified dopamine (DA) neurons (PDN) and the identification of factors relevant to their survival. Our goal was to genetically tag and purify by flow cytometry embryonic midbrain DA neurons from a transgenic mouse line carrying 11 kb of human tyrosine hydroxylase promoter driving expression of the enhanced green fluorescent protein (GFP) for studies in vivo and in vitro. A 99% purification of GFP+ cells was achiev...

  2. Purified mouse dopamine neurons thrive and function after transplantation into brain but require novel glial factors for survival in culture.

    Science.gov (United States)

    Donaldson, A E; Marshall, C E; Yang, Ming; Suon, S; Iacovitti, Lorraine

    2005-12-01

    Cell replacement therapy in Parkinson's disease depends on a reliable source of purified dopamine (DA) neurons (PDN) and the identification of factors relevant to their survival. Our goal was to genetically tag and purify by flow cytometry embryonic midbrain DA neurons from a transgenic mouse line carrying 11 kb of human tyrosine hydroxylase promoter driving expression of the enhanced green fluorescent protein(GFP) for studies in vivo and in vitro. A 99% purification of GFP+ cells was achieved. When transplanted into 6-hydroxydopamine-treated rat striatum, PDN survived, became well-integrated and produced recovery from amphetamine-induced motor behaviors. However, when grown in culture, PDN died within days of plating. No known growth factors prevented PDN death as did incubation with novel factors in glia/glial-conditioned media. We conclude that GFP-tagged DA neurons can be purified to homogeneity and can survive and function when grown with glial factors in vitro or after transplantation in vivo.

  3. Cytotoxicity of Botulinum Neurotoxins Reveals a Direct Role of Syntaxin 1 and SNAP-25 in Neuron Survival

    Science.gov (United States)

    Peng, Lisheng; Liu, Huisheng; Ruan, Hongyu; Tepp, William H.; Stoothoff, William H.; Brown, Robert H.; Johnson, Eric A.; Yao, Wei-Dong; Zhang, Su-Chun; Dong, Min

    2014-01-01

    Botulinum neurotoxins (BoNT/A-G) are well-known to act by blocking synaptic vesicle exocytosis. Whether BoNTs disrupt additional neuronal functions has not been addressed. Here we report that cleavage of syntaxin 1 (Syx 1) by BoNT/C and cleavage of SNAP-25 by BoNT/E both induce degeneration of cultured rodent and human neurons. Furthermore, although SNAP-25 cleaved by BoNT/A can still support neuron survival, it has reduced capacity to tolerate additional mutations and also fails to pair with syntaxin isoforms other than Syx 1. Syx 1 and SNAP-25 are well-known for mediating synaptic vesicle exocytosis, but we found that neuronal death is due to blockage of plasma membrane recycling processes that share Syx 1/SNAP-25 for exocytosis, independent of blockage of synaptic vesicle exocytosis. These findings reveal neuronal cytotoxicity for a subset of BoNTs and directly link Syx 1/SNAP-25 to neuron survival as the prevalent SNARE proteins mediating multiple fusion events on neuronal plasma membranes. PMID:23403573

  4. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  5. Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity

    Directory of Open Access Journals (Sweden)

    Martin Regensburger

    2014-01-01

    Full Text Available In Parkinson’s disease (PD and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.

  6. A novel cell immunoassay to measure survival of motor neurons protein in blood cells

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    Fischbeck Kenneth H

    2006-02-01

    Full Text Available Abstract Background The motor neuron degenerative disease spinal muscular atrophy (SMA is the leading genetic cause of infant mortality and is caused by mutations in the survival of motor neurons (SMN gene that reduce the expression levels of the SMN protein. A major goal of current therapeutic approaches is to increase SMN levels in SMA patients. The purpose of this study was to develop a reliable assay to measure SMN protein levels from peripheral blood samples. Methods We developed a novel cell immunoassay to quantitatively measure SMN levels from peripheral blood mononuclear cells (PBMCs using a single anti-SMN antibody. Results SMN levels determined by the cell immunoassay are comparable to levels determined by Western blot, but in contrast, the immunoassay does not involve cell lysis, requires a small amount of patient material, and can be done on a large number of samples simultaneously. SMN levels from PBMCs are not influenced by cell type heterogeneity. Conclusion SMN levels measured from total PBMCs provide an important snapshot of SMN protein expression, which should be a useful aid in SMA diagnosis, and a surrogate marker of efficacy of treatment in SMA clinical trials.

  7. The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly

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    Paul G. Donlin-Asp

    2017-02-01

    Full Text Available Spinal muscular atrophy (SMA is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs. SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3′ UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP complexes that associate with the cytoskeleton to facilitate trafficking. We have identified defects in mRNP assembly in cells and tissues from SMA disease models and patients that depend on the SMN Tudor domain and explain the observed deficiency in mRNA localization and local translation, providing insight into SMA pathogenesis as a ribonucleoprotein (RNP-assembly disorder.

  8. Retinoblastoma protein controls growth, survival and neuronal migration in human cerebral organoids.

    Science.gov (United States)

    Matsui, Takeshi; Nieto-Estévez, Vanesa; Kyrychenko, Sergii; Schneider, Jay W; Hsieh, Jenny

    2017-03-15

    The tumor suppressor retinoblastoma protein (RB) regulates S-phase cell cycle entry via E2F transcription factors. Knockout (KO) mice have shown that RB plays roles in cell migration, differentiation and apoptosis, in developing and adult brain. In addition, the RB family is required for self-renewal and survival of human embryonic stem cells (hESCs). Since little is known about the role of RB in human brain development, we investigated its function in cerebral organoids differentiated from gene-edited hESCs lacking RB. We show that RB is abundantly expressed in neural stem and progenitor cells in organoids at 15 and 28 days of culture. RB loss promoted S-phase entry in DCX + cells and increased apoptosis in Sox2 + neural stem and progenitor cells, and in DCX + and Tuj1 + neurons. Associated with these cell cycle and pro-apoptotic effects, we observed increased CCNA2 and BAX gene expression, respectively. Moreover, we observed aberrant Tuj1 + neuronal migration in RB-KO organoids and upregulation of the gene encoding VLDLR, a receptor important in reelin signaling. Corroborating the results in RB-KO organoids in vitro , we observed ectopically localized Tuj1 + cells in RB-KO teratomas grown in vivo Taken together, these results identify crucial functions for RB in the cerebral organoid model of human brain development. © 2017. Published by The Company of Biologists Ltd.

  9. TRANSGENIC GDNF POSITIVELY INFLUENCES PROLIFERATION, DIFFERENTIATION, MATURATION AND SURVIVAL OF MOTOR NEURONS PRODUCED FROM MOUSE EMBRYONIC STEM CELLS.

    Directory of Open Access Journals (Sweden)

    Daniel Édgar Cortés

    2016-09-01

    Full Text Available Embryonic stem cells (ESC are pluripotent and thus can differentiate into every cell type present in the body. Directed differentiation into motor neurons has been described for pluripotent cells. Although neurotrophic factors promote neuronal survival, their role in neuronal commitment is elusive. Here, we developed double-transgenic lines of mouse ESC that constitutively produce Glial cell-derived neurotrophic factor (GDNF and also contain a GFP reporter, driven by HB9, which is expressed only by postmitotic motor neurons. After lentiviral transduction, ESC lines integrated and expressed the human GDNF gene without altering pluripotency markers before differentiation. Further, GDNF-ESC showed significantly higher spontaneous release of this neurotrophin to the medium, when compared to controls. To study motor neuron induction, control and GDNF cell lines were grown as embryoid bodies and stimulated with retinoic acid and Sonic Hedgehog. In GDNF-overexpressing cells, a significant increase of proliferative Olig2+ precursors, which are specified as spinal motor neurons, was found. Accordingly, GDNF increases the yield of cells with the pan motor neuronal markers HB9, monitored by GFP expression, and Isl1. At terminal differentiation, almost all differentiated neurons express phenotypic markers of motor neurons in GDNF cultures, with lower proportions in control cells. To test if the effects of GDNF were present at early differentiation stages, exogenous recombinant human GDNF was added to control ESC, also resulting in enhanced motor neuron differentiation. This effect was abolished by the co-addition of neutralizing anti-GDNF antibodies, strongly suggesting that differentiating ESC are responsive to GDNF. Using the HB9::GFP reporter, motor neurons were selected for electrophysiological recordings. Motor neurons differentiated from GDNF-ESC, compared to control motor neurons, showed greater electrophysiological maturation, characterized by

  10. Evaluation of silver diamine fluoride application in children and factors associated with arrested caries survival

    Science.gov (United States)

    Chandra, L.; Rahardjo, A.; Adiatman, M.; Darwita, R.; Maharani, D. A.; Callea, M.

    2017-08-01

    Dental caries is one of the most prevalent infectious diseases in children in Indonesia. Therefore, a solution to overcome caries is needed. Evaluate Silver diamine fluoride (SDF) application for overcoming caries in children and determine factors related to the percentage of arrested caries after SDF application. Cohort study for evaluation and a cross-sectional study; 115 children aged 3-5 years who had active dentin caries were the subjects. Caries risk factors were measured by questionnaires filled out by subjects’ parents. Active caries treated with SDF had odds ratios of 9.9 and 6.8 of being arrested after 3 and 10 months, respectively, when compared with those not treated. Conclusion: SDF is effective in arresting caries and decreasing toothaches suffered by children, thus potentially increasing children’s quality of life.

  11. Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.

    Science.gov (United States)

    Nafar, F; Clarke, J P; Mearow, K M

    2017-05-01

    Alzheimer's disease is a progressive neurodegenerative disease that has links with other conditions that can often be modified by dietary and life-style interventions. In particular, coconut oil has received attention as having potentially having benefits in lessening the cognitive deficits associated with Alzheimer's disease. In a recent report, we showed that neuron survival in cultures co-treated with coconut oil and Aβ was rescued compared to cultures exposed only to Aβ. Here we investigated treatment with Aβ for 1, 6 or 24 h followed by addition of coconut oil for a further 24 h, or treatment with coconut oil for 24 h followed by Aβ exposure for various periods. Neuronal survival and several cellular parameters (cleaved caspase 3, synaptophysin labeling and ROS) were assessed. In addition, the influence of these treatments on relevant signaling pathways was investigated with Western blotting. In terms of the treatment timing, our data indicated that coconut oil rescues cells pre-exposed to Aβ for 1 or 6 h, but is less effective when the pre-exposure has been 24 h. However, pretreatment with coconut oil prior to Aβ exposure showed the best outcomes. Treatment with octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment. Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. This was supported by observations that a PI3-Kinase inhibitor blocked the rescue effect of CoOil on Aβ amyloid toxicity. Further studies into the mechanisms of action of coconut oil and its constituent medium chain fatty acids are warranted

  12. Amantadine improves cognitive outcome and increases neuronal survival after fluid percussion traumatic brain injury in rats.

    Science.gov (United States)

    Wang, Tao; Huang, Xian-Jian; Van, Ken C; Went, Gregory T; Nguyen, Jack T; Lyeth, Bruce G

    2014-02-15

    This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. Amantadine or saline control was administered intraperitoneally, starting at 1 h after TBI followed by dosing three times daily for 16 consecutive days at 15, 45, and 135 mg/kg/day. Terminal blood draws were obtained from TBI rats at the time of euthanasia at varying time points after the last amantadine dose. Pharmacokinetics analysis confirmed that the doses of AMT achieved serum concentrations similar to those observed in humans receiving therapeutic doses (100-400 mg/day). Acquisition of spatial learning and memory retention was assessed using the Morris water maze (MWM) on days 12-16 after TBI. Brain tissues were collected and stained with Cresyl-violet for long-term cell survival analysis. Treatment with 135mg/kg/day of AMT improved acquisition of learning and terminal cognitive performance on MWM. The 135-mg/kg/day dosing of AMT increased the numbers of surviving CA2-CA3 pyramidal neurons at day 16 post-TBI. Overall, the data showed that clinically relevant dosing schedules of AMT affords neuroprotection and significantly improves cognitive outcome after experimental TBI, suggesting that it has the potential to be developed as a novel treatment of human TBI.

  13. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin Volmer

    2003-01-01

    The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein...... kinase (MAPK) pathway and an increase in intracellular Ca2+ levels. Stimulation of neurones with the synthetic NCAM-ligand, C3, induces neurite outgrowth through signalling pathways similar to the pathways activated through physiological, homophilic NCAM-stimulation. We present here data indicating...... indicating a survival-promoting effect of NCAM-stimulation by C3 on cerebellar and dopaminergic neurones induced to undergo apoptosis. This protective effect of C3 included an inhibition of both DNA-fragmentation and caspase-3 activation. The survival-promoting effect of NCAM-stimulation was also shown...

  14. The Gemin associates of survival motor neuron are required for motor function in Drosophila.

    Directory of Open Access Journals (Sweden)

    Rebecca Borg

    Full Text Available Membership of the survival motor neuron (SMN complex extends to nine factors, including the SMN protein, the product of the spinal muscular atrophy (SMA disease gene, Gemins 2-8 and Unrip. The best-characterised function of this macromolecular machine is the assembly of the Sm-class of uridine-rich small nuclear ribonucleoprotein (snRNP particles and each SMN complex member has a key role during this process. So far, however, only little is known about the function of the individual Gemin components in vivo. Here, we make use of the Drosophila model organism to uncover loss-of-function phenotypes of Gemin2, Gemin3 and Gemin5, which together with SMN form the minimalistic fly SMN complex. We show that ectopic overexpression of the dead helicase Gem3(ΔN mutant or knockdown of Gemin3 result in similar motor phenotypes, when restricted to muscle, and in combination cause lethality, hence suggesting that Gem3(ΔN overexpression mimics a loss-of-function. Based on the localisation pattern of Gem3(ΔN, we predict that the nucleus is the primary site of the antimorphic or dominant-negative mechanism of Gem3(ΔN-mediated interference. Interestingly, phenotypes induced by human SMN overexpression in Drosophila exhibit similarities to those induced by overexpression of Gem3(ΔN. Through enhanced knockdown we also uncover a requirement of Gemin2, Gemin3 and Gemin5 for viability and motor behaviour, including locomotion as well as flight, in muscle. Notably, in the case of Gemin3 and Gemin5, such function also depends on adequate levels of the respective protein in neurons. Overall, these findings lead us to speculate that absence of any one member is sufficient to arrest the SMN-Gemins complex function in a nucleocentric pathway, which is critical for motor function in vivo.

  15. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

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    Young-Mi Lim

    Full Text Available Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1 is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1 and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.

  16. Regulation of tyrosine kinase B activity by the Cyp46/cholesterol loss pathway in mature hippocampal neurons: relevance for neuronal survival under stress and in aging.

    Science.gov (United States)

    Sodero, Alejandro O; Trovò, Laura; Iannilli, Francesca; Van Veldhoven, Paul; Dotti, Carlos G; Martin, Mauricio G

    2011-03-01

    It is well established that memory formation and retention involve the coordinated flow of information from the post-synaptic site of particular neuronal populations to the nucleus, where short and long-lasting modifications of gene expression occur. With age, mnemonic, motor and sensorial alterations occur, and it is believed that extra failures in the mechanisms used for memory formation and storage are the cause of neurodegenerative pathologies like Alzheimer's disease. A prime candidate responsible for damage and loss of function during aging is the accumulation of reactive oxygen species, derived from normal oxidative metabolism. However, dysfunction in the aged brain is not paralleled by an increase in neuronal death, indicative that the brain is better suited to fight against the death signals generated from reactive oxygen species than against loss-of-function stimuli. A main aim of this laboratory is to understand how neurons perform and survive in the constitutive stress background represented by aging. In this report, we summarize our recent findings in relation to survival. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  17. Activating transcription factor 5 (ATF5) is essential for the maturation and survival of mouse basal vomeronasal sensory neurons.

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    Nakano, Haruo; Iida, Yoshitaka; Suzuki, Makoto; Aoki, Marie; Umemura, Mariko; Takahashi, Shigeru; Takahashi, Yuji

    2016-03-01

    Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of transcription factors, which is highly expressed in olfactory chemosensory tissues, the main olfactory epithelium and vomeronasal epithelium (VNE) in mice. The vomeronasal sensory neurons in the VNE detect pheromones in order to regulate social behaviors such as mating and aggression; however, the physiological role of ATF5 in the vomeronasal sensory system remains unknown. In this study, we found that the differentiation of mature vomeronasal sensory neurons, assessed by olfactory marker protein expression, was inhibited in ATF5-deficient VNE. In addition, many apoptotic vomeronasal sensory neurons were evident in ATF5-deficient VNE. The vomeronasal sensory neurons consist of two major types of neuron expressing either vomeronasal 1 receptor (V1r)/Gαi2 or vomeronasal 2 receptor (V2r)/Gαo. We demonstrated that the differentiation, survival and axonal projection of V2r/Gαo-type rather than V1r/Gαi2-type vomeronasal sensory neurons were severely inhibited in ATF5-deficient VNE. These results suggest that ATF5 is one of the transcription factors crucial for the vomeronasal sensory formation.

  18. An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons

    DEFF Research Database (Denmark)

    Neiiendam, Johanne Louise; Køhler, Lene Boding; Christensen, Claus

    2004-01-01

    factor receptor (FGFR). NCAM-mediated adhesion leads to activation of various intracellular signal transduction pathways, including the Ras-mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PI3K)-Akt pathways. A synthetic peptide derived from the second fibronectin type III...... of the FGL peptide are shown to depend on activation of FGFR and the MAPK and PI3K intracellular signalling pathways, all three kinases being necessary for the effects of FGL on neurite outgrowth and neuronal survival....

  19. Molecular determinants of survival motor neuron (SMN protein cleavage by the calcium-activated protease, calpain.

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    Jennifer L Fuentes

    2010-12-01

    Full Text Available Spinal muscular atrophy (SMA is a leading genetic cause of childhood mortality, caused by reduced levels of survival motor neuron (SMN protein. SMN functions as part of a large complex in the biogenesis of small nuclear ribonucleoproteins (snRNPs. It is not clear if defects in snRNP biogenesis cause SMA or if loss of some tissue-specific function causes disease. We recently demonstrated that the SMN complex localizes to the Z-discs of skeletal and cardiac muscle sarcomeres, and that SMN is a proteolytic target of calpain. Calpains are implicated in muscle and neurodegenerative disorders, although their relationship to SMA is unclear. Using mass spectrometry, we identified two adjacent calpain cleavage sites in SMN, S192 and F193. Deletion of small motifs in the region surrounding these sites inhibited cleavage. Patient-derived SMA mutations within SMN reduced calpain cleavage. SMN(D44V, reported to impair Gemin2 binding and amino-terminal SMN association, drastically inhibited cleavage, suggesting a role for these interactions in regulating calpain cleavage. Deletion of A188, a residue mutated in SMA type I (A188S, abrogated calpain cleavage, highlighting the importance of this region. Conversely, SMA mutations that interfere with self-oligomerization of SMN, Y272C and SMNΔ7, had no effect on cleavage. Removal of the recently-identified SMN degron (Δ268-294 resulted in increased calpain sensitivity, suggesting that the C-terminus of SMN is important in dictating availability of the cleavage site. Investigation into the spatial determinants of SMN cleavage revealed that endogenous calpains can cleave cytosolic, but not nuclear, SMN. Collectively, the results provide insight into a novel aspect of the post-translation regulation of SMN.

  20. Potential Involvement of Snail Members in Neuronal Survival and Astrocytic Migration during the Gecko Spinal Cord Regeneration

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    Yongjun Wang

    2017-04-01

    Full Text Available Certain regenerative vertebrates such as fish, amphibians and reptiles are capable of regenerating spinal cord after injury. Most neurons of spinal cord will survive from the injury and regrow axons to repair circuits with an absence of glial scar formation. However, the underlying mechanisms of neuronal anti-apoptosis and glia-related responses have not been fully clarified during the regenerative process. Gecko has becoming an inspiring model to address spinal cord regeneration in amniotes. In the present study, we investigated the regulatory roles of Snail family members, the important transcriptional factors involved in both triggering of the cell migration and cell survival, during the spontaneous spinal cord regeneration. Both Snail1 and Snail3 have been shown to promote neuronal survival and astrocytic migration via anti-apoptotic and GTPases signaling following gecko tail amputation. Transforming growth factor-beta (TGFβ, together with other cytokines were involved in inducing expression of Snail protein. Our data indicate a conserved function of Snail proteins in embryonic development and tissue regeneration, which may provide clues for CNS repair in the mammals.

  1. (R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model.

    Science.gov (United States)

    Weng, Yi-Hsin; Chen, Chu-Yu; Lin, Kun-Jun; Chen, Ying-Ling; Yeh, Tu-Hsueh; Hsiao, Ing-Tsung; Chen, Ing-Jou; Lu, Chin-Song; Wang, Hung-Li

    2016-01-01

    Mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our results suggest that altered expression of these genes involved in regulating neuronal survival may contribute to the pathogenesis of (R1441C) LRRK2-induced PD. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.

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    Taesup Cho

    Full Text Available Neural stem cell (NSC replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP, one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR via systemic application of the receptor antagonist, 3-[(R-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP. Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF and its consequent activation of tropomysosin receptor kinase B (TrkB receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases.

  3. ATF6alpha promotes astroglial activation and neuronal survival in a chronic mouse model of Parkinson's disease.

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    Koji Hashida

    Full Text Available Accumulating evidence suggests a crucial role for the unfolded protein response (UPR in Parkinson's disease (PD. In this study, we investigated the relevance of the UPR in a mouse model of chronic MPTP/probenecid (MPTP/P injection, which causes severe and persistent degeneration of dopaminergic neurons. Enhanced activation of the UPR branches, including ATF6α and PERK/eIF2α/ATF4, was observed after MPTP/P injections into mice. Deletion of the ATF6α gene accelerated neuronal degeneration and ubiquitin accumulation relatively early in the MPTP/P injection course. Surprisingly, astroglial activation was strongly suppressed, and production of the brain-derived neurotrophic factor (BDNF and anti-oxidative genes, such as heme oxygenase-1 (HO-1 and xCT, in astrocytes were reduced in ATF6α -/- mice after MPTP/P injections. Decreased BDNF expression in ATF6α -/- mice was associated with decreased expression of GRP78, an ATF6α-dependent molecular chaperone in the ER. Decreased HO-1 and xCT levels were associated with decreased expression of the ATF4-dependent pro-apoptotic gene CHOP. Consistent with these results, administration of the UPR-activating reagent tangeretin (5,6,7,8,4'-pentamethoxyflavone; IN19 into mice enhanced the expression of UPR-target genes in both dopaminergic neurons and astrocytes, and promoted neuronal survival after MPTP/P injections. These results suggest that the UPR is activated in a mouse model of chronic MPTP/P injection, and contributes to the survival of nigrostriatal dopaminergic neurons, in part, through activated astrocytes.

  4. PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.

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    Alison Wood-Kaczmar

    2008-06-01

    Full Text Available Parkinson's disease (PD is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.

  5. Spatial learning and neurogenesis: Effects of cessation of wheel running and survival of novel neurons by engagement in cognitive tasks.

    Science.gov (United States)

    Motta-Teixeira, Lívia Clemente; Takada, Silvia Honda; Machado-Nils, Aline Vilar; Nogueira, Maria Inês; Xavier, Gilberto Fernando

    2016-06-01

    Physical exercise stimulates cell proliferation in the adult dentate gyrus and facilitates acquisition and/or retention of hippocampal-dependent tasks. It is established that regular physical exercise improves cognitive performance. However, it is unclear for how long these benefits last after its interruption. Independent groups of rats received both free access to either unlocked (EXE Treatment) or locked (No-EXE Treatment) running wheels for 7 days, and daily injections of bromodeoxyuridine (BrdU) in the last 3 days. After a time delay period of either 1, 3, or 6 weeks without training, the animals were tested in the Morris water maze (MWM) either in a working memory task dependent on hippocampal function (MWM-HD) or in a visible platform searching task, independent on hippocampal function (MWM-NH). Data confirmed that exposure of rats to 7 days of spontaneous wheel running increases cell proliferation and neurogenesis. In contrast, neurogenesis was not accompanied by significant improvements of performance in the working memory version of the MWM. Longer time delays between the end of exercise and the beginning of cognitive training in the MWM resulted in lower cell survival; that is, the number of novel surviving mature neurons was decreased when this delay was 6 weeks as compared with when it was 1 week. In addition, data showed that while exposure to the MWM-HD working memory task substantially increased survival of novel neurons, exposure to the MWM-NH task did not, thus indicating that survival of novel dentate gyrus neurons depends on the engagement of this brain region in performance of cognitive tasks. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. The water extract of Liuwei dihuang possesses multi-protective properties on neurons and muscle tissue against deficiency of survival motor neuron protein.

    Science.gov (United States)

    Tseng, Yu-Ting; Jong, Yuh-Jyh; Liang, Wei-Fang; Chang, Fang-Rong; Lo, Yi-Ching

    2017-10-15

    Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease. This study aimed to investigate the potential protection of LWDH-WE on SMN deficiency-induced neurodegeneration and muscle weakness. The effects of LWDH-WE on SMN deficiency-induced neurotoxicity and muscle atrophy were examined by using SMN-deficient NSC34 motor neuron-like cells and SMA-like mice, respectively. Inducible SMN-knockdown NSC34 motor neuron-like cells were used to mimic SMN-deficient condition. Doxycycline (1 µg/ml) was used to induce SMN deficiency in stable NSC34 cell line carrying SMN-specific shRNA. SMAΔ7 mice were used as a severe type of SMA mouse model. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Apoptotic cells and neurite length were observed by inverted microscope. Protein expressions were examined by western blots. Muscle strength of animals was evaluated by hind-limb suspension test. LWDH-WE significantly increased SMN protein level, mitochondrial membrane potential and cell viability of SMN-deficient NSC34 cells. LWDH-WE attenuated SMN deficiency-induced down-regulation of B-cell lymphoma-2 (Bcl-2) and up-regulation of cytosolic cytochrome c and cleaved caspase-3. Moreover, LWDH-WE prevented SMN deficiency-induced inhibition of neurite outgrowth and activation of Ras homolog gene family, member A (RhoA)/ Rho-associated protein kinase (ROCK2)/ phospho

  7. trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation

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    Yan Fu

    2017-01-01

    Full Text Available Background. Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled. trans-cinnamaldehyde (TCA isolated from the stem bark of Cinnamomum cassia possesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells. Results. To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS- induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1β and recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects. Conclusions. Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

  8. Netrin-1 Mediates Neuronal Survival Through PIKE-L Interaction With the Dependence Receptor UNC5B

    Science.gov (United States)

    Tang, Xiaoling; Jang, Sung-Wuk; Okada, Masashi; Chan, Chi-Bun; Feng, Yue; Liu, Yu; Luo, Shi-Wen; Hong, Yan; Rama, Nicolas; Xiong, Wen-cheng; Mehlen, Patrick; Ye, Keqiang

    2010-01-01

    Netrins, a family of secreted molecules, play critical roles in axon guidance and cell migration during neuronal development 1,2. In addition to its role as a chemotropic molecule, netrin-1 also acts as a survival factor 3–7. Both UNC5 (i.e. UNC5A, B, C or D) and DCC are transmembrane receptors for netrin-18,9. In the absence of netrin-1, DCC and UNC5 act as dependence receptors and trigger apoptosis 3,6,10. However, how netrin-1 suppresses the apoptotic activity of the receptors remains elusive. Here, we show that netrin-1 induces interaction of UNC5B with the brain specific GTPase PIKE-L. This interaction triggers activation of PI 3-kinase signaling, prevents UNC5B’s pro-apoptotic activity and enhances neuronal survival. Moreover, this process tightly relies on Fyn as PIKE-L is tyrosine phosphorylated in response to netrin-1 and the netrin-1-mediated interaction of UNC5B with PIKE-L is inhibited in Fyn null mice. Thus, PIKE-L acts as a downstream survival effector for netrin-1 through UNC5B in the nervous system. PMID:18469807

  9. Inhibition of the Jak-STAT pathway prevents CNTF-mediated survival of axotomized oxytocinergic magnocellular neurons in organotypic cultures of the rat supraoptic nucleus

    Science.gov (United States)

    Askvig, Jason M.; Lo, David Y.; Sudbeck, Adam W.; Behm, Kathryn E.; Leiphon, Laura J.; Watt, John A.

    2012-01-01

    Previous studies have demonstrated that ciliary neurotrophic factor (CNTF) enhances survival and process outgrowth from magnocellular neurons in the paraventricular (PVN) and the supraoptic (SON) nuclei. However, the mechanisms by which CNTF facilitates these processes remain to be determined. Therefore, the aim of this study was to identify the immediate signal transduction events that occur within the rat SON following administration of exogenous rat recombinant CNTF (rrCNTF) and to determine the contribution of those intracellular signaling pathway(s) to neuronal survival and process outgrowth, respectively. Immunohistochemical and Western blot analysis demonstrated that axonal injury and acute unilateral pressure injection of 100 ng/μl of rrCNTF directly over the rat SON resulted in a rapid and transient increase in phosphorylated-STAT3 (pSTAT3) in astrocytes but not neurons in the SON in vivo. Utilizing rat hypothalamic organotypic explant cultures, we then demonstrated that administration of 25 ng/ml rrCNTF for 14 days significantly increased the survival and process outgrowth of OT magnocellular neurons. In addition, pharmacological inhibition of the Jak-STAT pathway via AG490 and cucurbitacin I significantly reduced the survival of OT magnocellular neurons in the SON and PVN; however, the contribution of the Jak-STAT pathway to CNTF-mediated process outgrowth remains to be determined. Together, these data indicate that CNTF-induced survival of OT magnocellular neurons is mediated indirectly through astrocytes via the Jak-STAT signaling pathway. PMID:23123407

  10. The contribution of ciliary neurotrophic factor receptors to adult motor neuron survival in vivo is specific to insult type and distinct from that for embryonic motor neurons.

    Science.gov (United States)

    Lee, Nancy; Rydyznski, Carolyn E; Spearry, Rachel P; Robitz, Rachel; Maclennan, A John

    2013-10-01

    Exogenous ciliary neurotrophic factor (CNTF) promotes motor neuron (MN) survival following trauma and in genetic models of MN disease. Unconditional disruption of the mouse CNTF receptor α (CNTFRα) gene leads to MN loss, demonstrating a developmental role for endogenous CNTF receptor signaling. These data also suggest that CNTF receptors may promote adult MN survival and that appropriately manipulating the receptors could effectively treat adult MN disorders. This effort would greatly benefit from a better understanding of the roles played by CNTF receptors in adult MNs. We have previously found that adult onset disruption of CNTFRα in facial MNs of "floxed CNTFRα" mice by AAV-Cre vector injection leads to significantly more MN loss than in identically treated controls. While indicating that CNTF receptors can promote adult MN survival, the data did not distinguish between potential roles in MN maintenance versus roles in protecting MNs from the injection associated trauma or the toxicity of the chronic Cre recombinase (Cre) produced by the AAV-Cre. Here we used an inducible Cre gene construct to produce adult-onset CNTFRα disruption in facial MNs without the traumatic and toxic effects of the AAV-Cre procedure. The MNs survive without CNTFRα, even when challenged by facial nerve crush or the injection-associated trauma, thereby suggesting, in conjunction with our previous study, that endogenous CNTF receptor signaling can protect MNs against toxic insult, such as that produced by chronic Cre. The data also indicate that in vivo CNTF receptors play very different roles in adult and embryonic MNs. © 2013 Wiley Periodicals, Inc.

  11. Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

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    Florence Kermen

    Full Text Available BACKGROUND: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days, but not a massed (within day, learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. CONCLUSION/SIGNIFICANCE: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

  12. Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant Loechrig.

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    Mandy Cook

    Full Text Available loechrig (loe mutant flies are characterized by progressive neuronal degeneration, behavioral deficits, and early death. The mutation is due to a P-element insertion in the gene for the γ-subunit of the trimeric AMP-activated protein kinase (AMPK complex, whereby the insertion affects only one of several alternative transcripts encoding a unique neuronal isoform. AMPK is a cellular energy sensor that regulates a plethora of signaling pathways, including cholesterol and isoprenoid synthesis via its downstream target hydroxy-methylglutaryl (HMG-CoA reductase. We recently showed that loe interferes with isoprenoid synthesis and increases the prenylation and thereby activation of RhoA. During development, RhoA plays an important role in neuronal outgrowth by activating a signaling cascade that regulates actin dynamics. Here we show that the effect of loe/AMPKγ on RhoA prenylation leads to a hyperactivation of this signaling pathway, causing increased phosphorylation of the actin depolymerizating factor cofilin and accumulation of filamentous actin. Furthermore, our results show that the resulting cytoskeletal changes in loe interfere with neuronal growth and disrupt axonal integrity. Surprisingly, these phenotypes were enhanced by expressing the Slingshot (SSH phosphatase, which during development promotes actin depolymerization by dephosphorylating cofilin. However, our studies suggest that in the adult SSH promotes actin polymerization, supporting in vitro studies using human SSH1 that suggested that SSH can also stabilize and bundle filamentous actin. Together with the observed increase in SSH levels in the loe mutant, our experiments suggest that in mature neurons SSH may function as a stabilization factor for filamentous actin instead of promoting actin depolymerization.

  13. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

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    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  14. A Three-Dimensional Culture System with Matrigel Promotes Purified Spiral Ganglion Neuron Survival and Function In Vitro.

    Science.gov (United States)

    Yan, Wenqing; Liu, Wenwen; Qi, Jieyu; Fang, Qiaojun; Fan, Zhaomin; Sun, Gaoying; Han, Yuechen; Zhang, Daogong; Xu, Lei; Wang, Mingming; Li, Jianfeng; Chen, Fangyi; Liu, Dong; Chai, Renjie; Wang, Haibo

    2017-03-10

    In vitro culture of spiral ganglion neurons (SGNs) is a useful approach to investigate numerous aspects of neuronal behavior and to identify potential therapeutic targets for SGN protection and regeneration. However, the isolation of SGNs and the long-term maintenance of their structure and function in vitro remain challenging. In this study, we isolated SGNs from Bhlhb5-cre and Rosa26-tdTomato mice with fluorescence-activated cell sorting and determined the cell purity. We then encapsulated the pure SGNs in matrigel and cultured the SGNs in vitro. We found that the three-dimensional (3D)-matrigel culture environment significantly suppressed apoptosis and improved SGN survival in vitro, which enabled the long-term culture of SGNs for up to 6 months. The 3D-matrigel system also significantly promoted neurite outgrowth of the SGNs, increased the cells' polarity, promoted the area of growth cones, and significantly increased the synapse density of the SGNs. More importantly, the 3D-matrigel system helped to maintain and promote the electrophysiological properties of the SGNs. In conclusion, the 3D-matrigel culture system promoted the survival of purified SGNs in vitro and maintained their morphological structure and function and thus could be a useful tool for studying the physiology and pathophysiology of purified SGNs in long-term culture.

  15. Action potential changes associated with the inhibitory effects on voltage-gated sodium current of hippocampal CA1 neurons by silver nanoparticles.

    Science.gov (United States)

    Liu, Zhaowei; Ren, Guogang; Zhang, Tao; Yang, Zhuo

    2009-10-29

    Nano-sized materials are now being used in medicine, biotechnology, energy, and environmental technology. Although a wide and growing number of applications for nanomaterials exist, there are limited studies available on toxicity of nanoparticles for their human risk and environmental assessment. The aim of this study was to investigate the effects of silver nanoparticles (nano-Ag) on voltage-activated sodium currents in hippocampal CA1 neurons. Nano-Ag was tested at increasing concentrations (10(-6), 5 x 10(-6), 10(-5) g/ml). The research results showed that only nano-Ag (10(-5) g/ml) reduced the amplitude of voltage-gated sodium current (I(Na)). The nano-Ag particles produced a hyperpolarizing shift in the activation-voltage curve of I(Na) and also delayed the recovery of I(Na) from inactivation. Action potential properties and the pattern of repetitive firing were examined using whole cell current-clamp recordings. Peak amplitude and overshoot of the evoked single action potential were decreased and half-width was increased in the present of the 10(-5) g/ml nano-Ag solution, and the firing rate of repetitive firing had no change. The results suggest that nano-Ag may alter the action potential of hippocampal CA1 neurons by depressing voltage-gated sodium current.

  16. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Müller Anke

    2010-06-01

    Full Text Available Abstract Background Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC and Cannabidiol (CBD fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1 deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail. Results THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX-expressing intermediate progenitor cells. Conclusion CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.

  17. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats.

    Science.gov (United States)

    Cai, Jingli; Yang, Ming; Poremsky, Elizabeth; Kidd, Sarah; Schneider, Jay S; Iacovitti, Lorraine

    2010-07-01

    Cell replacement therapy could be an important treatment strategy for Parkinson's disease (PD), which is caused by the degeneration of dopamine neurons in the midbrain (mDA). The success of this approach greatly relies on the discovery of an abundant source of cells capable of mDAergic function in the brain. With the paucity of available human fetal tissue, efforts have increasingly focused on renewable stem cells. Human induced pluripotent stem (hiPS) cells offer great promise in this regard. If hiPS cells can be differentiated into authentic mDA neuron, hiPS could provide a potential autologous source of transplant tissue when generated from PD patients, a clear advantage over human embryonic stem (hES) cells. Here, we report that mDA neurons can be derived from a commercially available hiPS cell line, IMR90 clone 4, using a modified hES differentiation protocol established in our lab. These cells express all the markers (Lmx1a, Aldh1a1, TH, TrkB), follow the same mDA lineage pathway as H9 hES cells, and have similar expression levels of DA and DOPAC. Moreover, when hiPS mDA progenitor cells are transplanted into 6-OHDA-lesioned PD rats, they survive long term and many develop into bona fide mDA neurons. Despite their differentiation and integration into the brain, many Nestin+ tumor-like cells remain at the site of the graft. Our data suggest that as with hES cells, selecting the appropriate population of mDA lineage cells and eliminating actively dividing hiPS cells before transplantation will be critical for the future success of hiPS cell replacement therapy in PD patients.

  18. The melanoma-linked "redhead" MC1R influences dopaminergic neuron survival.

    Science.gov (United States)

    Chen, Xiqun; Chen, Hongxiang; Cai, Waijiao; Maguire, Michael; Ya, Bailiu; Zuo, Fuxing; Logan, Robert; Li, Hui; Robinson, Katey; Vanderburg, Charles R; Yu, Yang; Wang, Yinsheng; Fisher, David E; Schwarzschild, Michael A

    2017-03-01

    Individuals with Parkinson disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo. Genetic and pharmacological approaches were employed to manipulate MC1R, and nigrostriatal dopaminergic integrity was determined by comprehensive behavioral, neurochemical, and neuropathological measures. MC1Re/e mice, which carry an inactivating mutation of MC1R and mimic the human redhead phenotype, have compromised nigrostriatal dopaminergic neuronal integrity, and they are more susceptible to dopaminergic neuron toxins 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, a selective MC1R agonist protects against MPTP-induced dopaminergic neurotoxicity. Our findings reveal a protective role of MC1R in the nigrostriatal dopaminergic system, and they provide a rationale for MC1R as a potential therapeutic target for Parkinson disease. Together with its established role in melanoma, MC1R may represent a common pathogenic pathway for melanoma and Parkinson disease. Ann Neurol 2017;81:395-406. © 2016 American Neurological Association.

  19. Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Asmussen, Johanne W; Lindstam, Mats

    2007-01-01

    of cell death (Bim(S)). Finally, evidence is provided that MT and EmtinB activate extracellular signal-regulated kinase, protein kinase B, and cAMP response element binding protein. Altogether, these results strongly suggest that MT and EmtinB induce their neuronal effects through direct binding......Accumulating evidence suggests that metallothionein (MT)-I and -II promote neuronal survival and regeneration in vivo. The present study investigated the molecular mechanisms underlying the differentiation and survival-promoting effects of MT and a peptide modeled after MT, EmtinB. Both MT...... and EmtinB directly stimulated neurite outgrowth and promoted survival in vitro using primary cultures of cerebellar granule neurons. In addition, expression and surface localization of megalin, a known MT receptor, and the related lipoprotein receptor-related protein-1 (LRP) are demonstrated in cerebellar...

  20. Differential Neuronal Vulnerability varies according to Specific Cardiopulmonary Bypass Insult in a Porcine Survival Model

    Science.gov (United States)

    Ishibashi, Nobuyuki; Iwata, Yusuke; Okamura, Toru; Zurakowski, David; Lidov, Hart G.W.; Jonas, Richard A.

    2010-01-01

    Objective We investigated whether the degree of vulnerability of different areas in the developing brain varies according to the specific mechanism of the insults caused by cardiopulmonary bypass. Methods A meta-analysis of two experimental studies (n = 80) was conducted. The end points of the otherwise identical studies were tissue oxygen index in experiment one while cerebral micro-vessel vasoconstriction and inflammatory response of endothelial cells were directly visualized in the second study. We assigned ultra-low flow bypass at 25°C for 60 min as Control; circulatory arrest at 25°C for 60 min as ischemic stress under circulatory arrest (Ischemia-CA); and ultra-low flow bypass at 34°C for 60 min as the stress under ultra-low flow bypass (Ischemia-ULF). Histological neuronal damage was the primary outcome. Secondary measures included neurological recovery. Results Vasoconstriction following ischemia and inflammation after bypass were independent predictors of severe histological damage. The caudate nucleus was significantly vulnerable to Ischemia-CA and was significantly influenced by vasoconstriction. In contrast, the hippocampus was significantly vulnerable to Ischemia-ULF. The different forms of ischemic insults did not influence Purkinje cells, while Purkinje damage significantly correlated with inflammation. Tissue oxygen index had the ability to differentiate accurately regional damage. Neurological recovery under Ischemia-CA was significantly worse compared with Ischemia-ULF. Neurological recovery correlated with neuronal damage in the caudate nucleus, but did not correlate with damage in the hippocampus. Conclusion Neuronal vulnerability in different areas of the developing brain varies according to mechanisms of bypass-induced ischemic stress. Certain regional damage may not be apparent in assessing acute neurological recovery. PMID:20434176

  1. Newborn neurons in the olfactory bulb selected for long-term survival through olfactory learning are prematurely suppressed when the olfactory memory is erased.

    Science.gov (United States)

    Sultan, Sébastien; Rey, Nolwen; Sacquet, Joelle; Mandairon, Nathalie; Didier, Anne

    2011-10-19

    A role for newborn neurons in olfactory memory has been proposed based on learning-dependent modulation of olfactory bulb neurogenesis in adults. We hypothesized that if newborn neurons support memory, then they should be suppressed by memory erasure. Using an ecological approach in mice, we showed that behaviorally breaking a previously learned odor-reward association prematurely suppressed newborn neurons selected to survive during initial learning. Furthermore, intrabulbar infusions of the caspase pan-inhibitor ZVAD (benzyloxycarbonyl-Val-Ala-Asp) during the behavioral odor-reward extinction prevented newborn neurons death and erasure of the odor-reward association. Newborn neurons thus contribute to the bulbar network plasticity underlying long-term memory.

  2. RhoA as a target to promote neuronal survival and axon regeneration

    Directory of Open Access Journals (Sweden)

    Jianli Hu

    2017-01-01

    Full Text Available Paralysis following spinal cord injury (SCI is due to failure of axonal regeneration. It is believed that the capacities of neurons to regrow their axons are due partly to their intrinsic characteristics, which in turn are greatly influenced by several types of inhibitory molecules that are present, or even increased in the extracellular environment of the injured spinal cord. Many of these inhibitory molecules have been studied extensively in recent years. It has been suggested that the small GTPase RhoA is an intracellular convergence point for signaling by these extracellular inhibitory molecules, but due to the complexity of the central nervous system (CNS in mammals, and the limitation of pharmacological tools, the specific roles of RhoA are unclear. By exploiting the anatomical and technical advantages of the lamprey CNS, we recently demonstrated that RhoA knockdown promotes true axon regeneration through the lesion site after SCI. In addition, we found that RhoA knockdown protects the large, identified reticulospinal neurons from apoptosis after their axons were axotomized in spinal cord. Therefore, manipulation of the RhoA signaling pathway may be an important approach in the development of treatments that are both neuroprotective and axon regeneration-promoting, to enhance functional recovery after SCI.

  3. Survival of motor neurone protein is required for normal postnatal development of the spleen.

    Science.gov (United States)

    Thomson, Alison K; Somers, Eilidh; Powis, Rachael A; Shorrock, Hannah K; Murphy, Kelley; Swoboda, Kathryn J; Gillingwater, Thomas H; Parson, Simon H

    2017-02-01

    Spinal muscular atrophy (SMA), traditionally described as a predominantly childhood form of motor neurone disease, is the leading genetic cause of infant mortality. Although motor neurones are undoubtedly the primary affected cell type, the severe infantile form of SMA (Type I SMA) is now widely recognised to represent a multisystem disorder where a variety of organs and systems in the body are also affected. Here, we report that the spleen is disproportionately small in the 'Taiwanese' murine model of severe SMA (Smn -/- ;SMN2 tg/0 ), correlated to low levels of cell proliferation and increased cell death. Spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganised fibrotic architecture. Histologically distinct white pulp failed to form and this was reflected in an almost complete absence of B lymphocytes necessary for normal immune function. In addition, megakaryoctyes persisted in the red pulp. However, the vascular density remained unchanged in SMA spleen. Assessment of the spleen in SMA patients with the infantile form of the disease indicated a range of pathologies. We conclude that development of the spleen fails to occur normally in SMA mouse models and human patients. Thus, further analysis of immune function is likely to be required to fully understand the full extent of systemic disease pathology in SMA. © 2016 Anatomical Society.

  4. Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases

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    Matthew E R Butchbach

    2016-03-01

    Full Text Available Proximal spinal muscular atrophy (SMA, a leading genetic cause of infant death worldwide, is an early-onset, autosomal recessive neurodegenerative disease characterized by the loss of spinal α-motor neurons. This loss of α-motor neurons is associated with muscle weakness and atrophy. SMA can be classified into five clinical grades based on age of onset and severity of the disease. Regardless of clinical grade, proximal SMA results from the loss or mutation of SMN1 (survival motor neuron 1 on chromosome 5q13. In humans a large tandem chromosomal duplication has lead to a second copy of the SMN gene locus known as SMN2. SMN2 is distinguishable from SMN1 by a single nucleotide difference that disrupts an exonic splice enhancer in exon 7. As a result, most of SMN2 mRNAs lack exon 7 (SMNΔ7 and produce a protein that is both unstable and less than fully functional. Although only 10-20% of the SMN2 gene product is fully functional, increased genomic copies of SMN2 inversely correlates with disease severity among individuals with SMA. Because SMN2 copy number influences disease severity in SMA, there is prognostic value in accurate measurement of SMN2 copy number from patients being evaluated for SMA. This prognostic value is especially important given that SMN2 copy number is now being used as an inclusion criterion for SMA clinical trials. In addition to SMA, copy number variations (CNVs in the SMN genes can affect the clinical severity of other neurological disorders including amyotrophic lateral sclerosis (ALS and progressive muscular atrophy (PMA. This review will discuss how SMN1 and SMN2 CNVs are detected and why accurate measurement of SMN1 and SMN2 copy numbers is relevant for SMA and other neurodegenerative diseases.

  5. Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus

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    Natalia Avaliani

    2017-01-01

    Full Text Available Direct conversion of human somatic cells to induced neurons (iNs, using lineage-specific transcription factors has opened new opportunities for cell therapy in a number of neurological diseases, including epilepsy. In most severe cases of epilepsy, seizures often originate in the hippocampus, where populations of inhibitory interneurons degenerate. Thus, iNs could be of potential use to replace these lost interneurons. It is not known, however, if iNs survive and maintain functional neuronal properties for prolonged time periods in in vivo. We transplanted human fibroblast-derived iNs into the adult rat hippocampus and observed a progressive morphological differentiation, with more developed dendritic arborisation at six months as compared to one month. This was accompanied by mature electrophysiological properties and fast high amplitude action potentials at six months after transplantation. This proof-of-principle study suggests that human iNs can be developed as a candidate source for cell replacement therapy in temporal lobe epilepsy.

  6. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  7. Dual and multi-drug delivery nanoparticles towards neuronal survival and synaptic repair

    Directory of Open Access Journals (Sweden)

    Angelina Angelova

    2017-01-01

    Full Text Available Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor (BDNF and its high-affinity tropomyosin-related kinase receptor (TrkB present strong interest for nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF is regarded as the neurotrophic factor of highest therapeutic significance. However, BDNF has delivery problems as a protein drug. The enhanced activation of the transcription factor CREB (cAMP response element-binding protein has been evidenced to increase the BDNF gene expression and hence the production of endogenous BDNF. We assume that BDNF delivery by nanocarriers and mitochondrial protection may provide high potential for therapeutic amelioration of the neuroregenerative strategies. Beneficial therapeutic outcomes may be expected for synergistic dual or multi-drug action aiming at (i neurotrophic protein regulation in the central and peripheral nervous systems, and (ii diminishment of the production of reactive oxygen species (ROS and the oxidative damage in mitochondria. Our research strategy is based on a nanoarchitectonics approach for the design of nanomedicine assemblies by hierarchical self-assembly. We explore nanoarchitectonics concepts in soft-matter nanotechnology towards preparation of biodegradable self-assembled lipid nanostructures for safe neuro-therapeutic applications of multi-target nanomedicines.

  8. Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy

    DEFF Research Database (Denmark)

    Schwartz, M; Sørensen, N; Hansen, F J

    1997-01-01

    In an analysis of 30 families affected by spinal muscular atrophy (SMA) we have used the solid-phase minisequencing method to determine the ratio between the number of telomeric and centromeric copies of the survival motor neuron gene (SMN and cBCD541 respectively) on normal and SMA chromosomes...

  9. Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Roland; Fransson, Anette; Fjord-Larsen, Lone

    2012-01-01

    properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast......Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved...... protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked...

  10. Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons.

    Science.gov (United States)

    Naoi, Makoto; Maruyama, Wakako; Shamoto-Nagai, Masayo

    2017-12-26

    Type A and B monoamine oxidases (MAO-A, -B) mediate and modulate intracellular signal pathways for survival or death of neuronal cells. MAO-A is associated with development of neuronal architecture, synaptic activity, and onset of psychiatric disorders, including depression, and antisocial aggressive impulsive behaviors. MAO-B produces hydrogen peroxide and plays a vital role in neuronal loss of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. This review presents a novel role of MAO-A and B, their substrates and inhibitors, and hydrogen peroxide in brain function and neuronal survival and death. MAO-A activity is regulated not only by genetic factor, but also by environmental factors, including stress, hormonal deregulation, and food factors. MAO-A activity fluctuates by genetic-environmental factors, modulates the neuronal response to the stimuli, and affects behavior and emotional activities. MAO-B inhibitors selegiline and rasagiline protect neurons via increase expression of anti-apoptotic Bcl-2 and pro-survival neurotrophic factors in human neuroblastoma SH-SY5Y and glioblastoma U118MG cell lines. MAO-A knockdown suppressed the rasagiline-induced gene expression in SH-SY5Y cells, whereas MAO-B silencing enhanced the basal- and selegiline-induced gene expression in U118MG cells. MAO-A and B were shown to function as a mediator or repressor of gene expression, respectively. Further study on cellular mechanism underlying regulation of signal pathways by MAO-A and B may bring us a new insight on the role of MAOs in decision of neuronal fate and the development of novel therapeutic strategy may be expected for neuropsychiatric disorders.

  11. Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kirby, Janine; Ning, Ke; Ferraiuolo, Laura; Heath, Paul R; Ismail, Azza; Kuo, Su-Wei; Valori, Chiara F; Cox, Laura; Sharrack, Basil; Wharton, Stephen B; Ince, Paul G; Shaw, Pamela J; Azzouz, Mimoun

    2011-02-01

    Gene expression profiling has been used previously with spinal cord homogenates and laser capture microdissected motor neurons to determine the mechanisms involved in neurodegeneration in amyotrophic lateral sclerosis. However, while cellular and animal model work has focused on superoxide dismutase 1-related amyotrophic lateral sclerosis, the transcriptional profile of human mutant superoxide dismutase 1 motor neurons has remained undiscovered. The aim of this study was to apply gene expression profiling to laser captured motor neurons from human superoxide dismutase 1-related amyotrophic lateral sclerosis and neurologically normal control cases, in order to determine those pathways dysregulated in human superoxide dismutase 1-related neurodegeneration and to establish potential pathways suitable for therapeutic intervention. Identified targets were then validated in cultured cell models using lentiviral vectors to manipulate the expression of key genes. Microarray analysis identified 1170 differentially expressed genes in spinal cord motor neurons from superoxide dismutase 1-related amyotrophic lateral sclerosis, compared with controls. These genes encoded for proteins in multiple functional categories, including those involved in cell survival and cell death. Further analysis determined that multiple genes involved in the phosphatidylinositol-3 kinase signalling cascade were differentially expressed in motor neurons that survived the disease process. Functional experiments in cultured cells and primary motor neurons demonstrate that manipulating this pathway by reducing the expression of a single upstream target, the negative phosphatidylinositol-3 kinase regulator phosphatase and tensin homology, promotes a marked pro-survival effect. Therefore, these data indicate that proteins in the phosphatidylinositol-3 kinase pathway could represent a target for therapeutic manipulation in motor neuron degeneration.

  12. Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

    Science.gov (United States)

    Jones, Clinton

    2013-01-01

    α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts. PMID:25278776

  13. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models.

    Science.gov (United States)

    Inoue, Haruhisa; Lin, Ling; Lee, Xinhua; Shao, Zhaohui; Mendes, Shannon; Snodgrass-Belt, Pamela; Sweigard, Harry; Engber, Tom; Pepinsky, Blake; Yang, Lichuan; Beal, M Flint; Mi, Sha; Isacson, Ole

    2007-09-04

    The nervous system-specific leucine-rich repeat Ig-containing protein LINGO-1 is associated with the Nogo-66 receptor complex and is endowed with a canonical EGF receptor (EGFR)-like tyrosine phosphorylation site. Our studies indicate that LINGO-1 expression is elevated in the substantia nigra of Parkinson's disease (PD) patients compared with age-matched controls and in animal models of PD after neurotoxic lesions. LINGO-1 expression is present in midbrain dopaminergic (DA) neurons in the human and rodent brain. Therefore, the role of LINGO-1 in cell damage responses of DA neurons was examined in vitro and in experimental models of PD induced by either oxidative (6-hydroxydopamine) or mitochondrial (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity. In LINGO-1 knockout mice, DA neuron survival was increased and behavioral abnormalities were reduced compared with WT. This neuroprotection was accompanied by increased Akt phosphorylation (p-Akt). Similar neuroprotective in vivo effects on midbrain DA neurons were obtained in WT mice by blocking LINGO-1 activity using LINGO-1-Fc protein. Neuroprotection and enhanced neurite growth were also demonstrated for midbrain DA neurons in vitro. LINGO-1 antagonists (LINGO-1-Fc, dominant negative LINGO-1, and anti-LINGO-1 antibody) improved DA neuron survival in response to MPP+ in part by mechanisms that involve activation of the EGFR/Akt signaling pathway through a direct inhibition of LINGO-1's binding to EGFR. These results show that inhibitory agents of LINGO-1 activity can protect DA neurons against degeneration and indicate a role for the leucine-rich repeat protein LINGO-1 and related classes of proteins in the pathophysiological responses of midbrain DA neurons in PD.

  14. Survival, excitability, and transfection of retinal neurons in an organotypic culture of mature zebrafish retina.

    Science.gov (United States)

    Kustermann, Stefan; Schmid, Susanne; Biehlmaier, Oliver; Kohler, Konrad

    2008-05-01

    Over the last 20 years, the zebrafish has become an important model organism for research on retinal function and development. Many retinal diseases do not become apparent until the later stages of life. This means that it is important to be able to analyze (gene) function in the mature retina. To meet this need, we have established an organotypic culture system of mature wild-type zebrafish retinas in order to observe changes in retinal morphology. Furthermore, cell survival during culture has been monitored by determining apoptosis in the tissue. The viability and excitability of ganglion cells have been tested at various time points in vitro by patch-clamp recordings, and retinal functionality has been assessed by measuring light-triggered potentials at the ganglion cell site. Since neurogenesis is persistent in adult zebrafish retinas, we have also monitored proliferating cells during culture by tracking their bromodeoxyuridine uptake. Reverse genetic approaches for probing the function of adult zebrafish retinas are not yet available. We have therefore established a rapid and convenient protocol for delivering plasmid DNA or oligonucleotides by electroporation to the retinal tissue in vitro. The organotypic culture of adult zebrafish retinas presented here provides a reproducible and convenient method for investigating the function of drugs and genes in the retina under well-defined conditions in vitro.

  15. Distinct Effects of miR-210 Reduction on Neurogenesis: Increased Neuronal Survival of Inflammation But Reduced Proliferation Associated with Mitochondrial Enhancement.

    Science.gov (United States)

    Voloboueva, Ludmila A; Sun, Xiaoyun; Xu, Lijun; Ouyang, Yi-Bing; Giffard, Rona G

    2017-03-15

    Neurogenesis is essential to brain development and plays a central role in the response to brain injury. Stroke and head trauma stimulate proliferation of endogenous neural stem cells (NSCs); however, the survival of young neurons is sharply reduced by postinjury inflammation. Cellular mitochondria are critical to successful neurogenesis and are a major target of inflammatory injury. Mitochondrial protection was shown to improve survival of young neurons. This study tested whether reducing cellular microRNA-210 (miR-210) would enhance mitochondrial function and improve survival of young murine neurons under inflammatory conditions. Several studies have demonstrated the potential of miR-210 inhibition to enhance and protect mitochondrial function through upregulation of mitochondrial proteins. Here, miR-210 inhibition significantly increased neuronal survival and protected the activity of mitochondrial enzymes cytochrome c oxidase and aconitase in differentiating NSC cultures exposed to inflammatory mediators. Unexpectedly, we found that reducing miR-210 significantly attenuated NSC proliferation upon induction of differentiation. Further investigation revealed that increased mitochondrial function suppressed the shift to primarily glycolytic metabolism and reduced mitochondrial length characteristic of dividing cells. Activation of AMP-regulated protein kinase-retinoblastoma signaling is important in NSC proliferation and the reduction of this activation observed by miR-210 inhibition is one mechanism contributing to the reduced proliferation. Postinjury neurogenesis occurs as a burst of proliferation that peaks in days, followed by migration and differentiation over weeks. Our studies suggest that mitochondrial protective miR-210 inhibition should be delayed until after the initial burst of proliferation, but could be beneficial during the prolonged differentiation stage.SIGNIFICANCE STATEMENT Increasing the success of endogenous neurogenesis after brain injury

  16. Survival of motor neuron protein downregulates miR-9 expression in patients with spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Li-Ting Wang

    2014-05-01

    Full Text Available Spinal muscular atrophy (SMA is a lethal hereditary disease caused by homozygous absence of the survival of the motor neuron (SMN 1 gene (SMN1, and it is the leading genetic cause of infant mortality. The severity of SMA is directly correlated with SMN protein levels in affected patients; however, the cellular regulatory mechanisms for SMN protein expression are not completely understood. In this study, we investigated the regulatory effects between SMN expression and miR-9a, a downstream noncoding small RNA. Using an inducible SMN short hairpin RNA interference (shRNAi system in NSC 34 and human skin fibroblast cells, cellular miR-9 levels and SMN protein repression were time-dependently upregulated. Conversely, cellular miR-9 levels decreased when HeLa cells were transfected with SMN protein fused with green fluorescent protein. In SMA-like mice spinal cords and human primary skin fibroblasts isolated from patients with different degrees of SMA, human SMN exhibited a disease severity-dependent decrease, whereas cellular miR-9 levels increased. These results clearly suggested that cellular SMN proteins regulated miR-9 expression and that miR-9 expression was related to SMA severity. Thus, miR-9 may be a marker for SMA prognosis.

  17. Direct effects of HIV-1 Tat on excitability and survival of primary dorsal root ganglion neurons: possible contribution to HIV-1-associated pain.

    Directory of Open Access Journals (Sweden)

    Xianxun Chi

    Full Text Available The vast majority of people living with human immunodeficiency virus type 1 (HIV-1 have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG neurons. We demonstrated that HIV-1 Tat triggered rapid and sustained enhancement of the excitability of small-diameter rat primary DRG neurons, which was accompanied by marked reductions in the rheobase and resting membrane potential (RMP, and an increase in the resistance at threshold (R(Th. Such Tat-induced DRG hyperexcitability may be a consequence of the inhibition of cyclin-dependent kinase 5 (Cdk5 activity. Tat rapidly inhibited Cdk5 kinase activity and mRNA production, and roscovitine, a well-known Cdk5 inhibitor, induced a very similar pattern of DRG hyperexcitability. Indeed, pre-application of Tat prevented roscovitine from having additional effects on the RMP and action potentials (APs of DRGs. However, Tat-mediated actions on the rheobase and R(Th were accelerated by roscovitine. These results suggest that Tat-mediated changes in DRG excitability are partly facilitated by Cdk5 inhibition. In addition, Cdk5 is most abundant in DRG neurons and participates in the regulation of pain signaling. We also demonstrated that HIV-1 Tat markedly induced apoptosis of primary DRG neurons after exposure for longer than 48 h. Together, this work indicates that HIV-1 proteins are capable of producing pain signaling through direct actions on excitability and survival of sensory neurons.

  18. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  19. Aging Triggers Cytoplasmic Depletion and Nuclear Translocation of the E3 Ligase Mahogunin: A Function for Ubiquitin in Neuronal Survival.

    Science.gov (United States)

    Benvegnù, Stefano; Mateo, María Inés; Palomer, Ernest; Jurado-Arjona, Jerónimo; Dotti, Carlos G

    2017-05-04

    A decline in proteasome function is causally connected to neuronal aging and aging-associated neuropathologies. By using hippocampal neurons in culture and in vivo, we show that aging triggers a reduction and a cytoplasm-to-nucleus redistribution of the E3 ubiquitin ligase mahogunin (MGRN1). Proteasome impairment induces MGRN1 monoubiquitination, the key post-translational modification for its nuclear entry. One potential mechanism for MGRN1 monoubiquitination is via progressive deubiquitination at the proteasome of polyubiquitinated MGRN1. Once in the nucleus, MGRN1 potentiates the transcriptional cellular response to proteotoxic stress. Inhibition of MGRN1 impairs ATF3-mediated neuronal responsiveness to proteosomal stress and increases neuronal stress, while increasing MGRN1 ameliorates signs of neuronal aging, including cognitive performance in old animals. Our results imply that, among others, the strength of neuronal survival in a proteasomal deterioration background, like during aging, depends on the fine-tuning of ubiquitination-deubiquitination. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effects of dibutyryl cyclic-AMP on survival and neuronal differentiation of neural stem/progenitor cells transplanted into spinal cord injured rats.

    Directory of Open Access Journals (Sweden)

    Howard Kim

    Full Text Available Neural stem/progenitor cells (NSPCs have great potential as a cell replacement therapy for spinal cord injury. However, poor control over transplant cell differentiation and survival remain major obstacles. In this study, we asked whether dibutyryl cyclic-AMP (dbcAMP, which was shown to induce up to 85% in vitro differentiation of NSPCs into neurons would enhance survival of transplanted NSPCs through prolonged exposure either in vitro or in vivo through the controlled release of dbcAMP encapsulated within poly(lactic-co-glycolic acid (PLGA microspheres and embedded within chitosan guidance channels. NSPCs, seeded in fibrin scaffolds within the channels, differentiated in vitro to betaIII-tubulin positive neurons by immunostaining and mRNA expression, in response to dbcAMP released from PLGA microspheres. After transplantation in spinal cord injured rats, the survival and differentiation of NSPCs was evaluated. Untreated NSPCs, NSPCs transplanted with dbcAMP-releasing microspheres, and NSPCs pre-differentiated with dbcAMP for 4 days in vitro were transplanted after rat spinal cord transection and assessed 2 and 6 weeks later. Interestingly, NSPC survival was highest in the dbcAMP pre-treated group, having approximately 80% survival at both time points, which is remarkable given that stem cell transplantation often results in less than 1% survival at similar times. Importantly, dbcAMP pre-treatment also resulted in the greatest number of in vivo NSPCs differentiated into neurons (37±4%, followed by dbcAMP-microsphere treated NSPCs (27±14% and untreated NSPCs (15±7%. The reverse trend was observed for NSPC-derived oligodendrocytes and astrocytes, with these populations being highest in untreated NSPCs. This combination strategy of stem cell-loaded chitosan channels implanted in a fully transected spinal cord resulted in extensive axonal regeneration into the injury site, with improved functional recovery after 6 weeks in animals implanted with

  1. Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning

    DEFF Research Database (Denmark)

    Køhler, Lene B; Christensen, Claus; Rossetti, Clara

    2010-01-01

    Neural cell adhesion molecule (NCAM)-mediated cell adhesion results in activation of intracellular signaling cascades that lead to cellular responses such as neurite outgrowth, neuronal survival, and modulation of synaptic activity associated with cognitive processes. The crystal structure...... of the immunoglobulin (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM homophilic adhesion. The present study addressed the biological significance of the so called dense zipper formation of NCAM. Two peptides, termed dennexinA and dennexinB, were modeled after the contact interfaces...... between Ig1 and Ig3 and between Ig2 and Ig2, respectively, observed in the crystal structure. Although the two dennexin peptides differed in amino acid sequence, they both modulated cell adhesion, reflected by inhibition of NCAM-mediated neurite outgrowth. Both dennexins also promoted neuronal survival...

  2. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

    Directory of Open Access Journals (Sweden)

    Chung-Hsiang Liu

    2012-01-01

    Full Text Available Uncaria rhynchophylla (UR, which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA- induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus

  3. The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C.

    Science.gov (United States)

    Loers, Gabriele; Astafiev, Steven; Hapiak, Yuliya; Saini, Vedangana; Mishra, Bibhudatta; Gul, Sheraz; Kaur, Gurcharan; Schachner, Melitta; Theis, Thomas

    2017-08-01

    Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues. It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM). PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions. In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury. In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay. Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735. Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries. © 2017 International Society for Neurochemistry.

  4. Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss.

    Science.gov (United States)

    He, Qiang; Jia, Zhanwei; Zhang, Ying; Ren, Xiumin

    2017-03-01

    We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin-induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  5. Kidins220/ARMS downregulation by excitotoxic activation of NMDARs reveals its involvement in neuronal survival and death pathways

    National Research Council Canada - National Science Library

    López-Menéndez, Celia; Gascón, Sergio; Sobrado, Mónica; Vidaurre, Oscar G; Higuero, Alonso M; Rodríguez-Peña, Angeles; Iglesias, Teresa; Díaz-Guerra, Margarita

    2009-01-01

    .... Here, we identify an association between these proteins and discover that excitotoxicity, a specific form of neuronal death induced by NMDAR overstimulation, dramatically decreases Kidins220/ARMS...

  6. Extracellular vesicles from a muscle cell line (C2C12 enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34

    Directory of Open Access Journals (Sweden)

    Roger D. Madison

    2014-02-01

    Full Text Available Introduction: There is renewed interest in extracellular vesicles over the past decade or 2 after initially being thought of as simple cellular garbage cans to rid cells of unwanted components. Although there has been intense research into the role of extracellular vesicles in the fields of tumour and stem cell biology, the possible role of extracellular vesicles in nerve regeneration is just in its infancy. Background: When a peripheral nerve is damaged, the communication between spinal cord motor neurons and their target muscles is disrupted and the result can be the loss of coordinated muscle movement. Despite state-of-the-art surgical procedures only approximately 10% of adults will recover full function after peripheral nerve repair. To improve upon such results will require a better understanding of the basic mechanisms that influence axon outgrowth and the interplay between the parent motor neuron and the distal end organ of muscle. It has previously been shown that extracellular vesicles are immunologically tolerated, display targeting ligands on their surface, and can be delivered in vivo to selected cell populations. All of these characteristics suggest that extracellular vesicles could play a significant role in nerve regeneration. Methods: We have carried out studies using 2 very well characterized cell lines, the C2C12 muscle cell line and the motor neuron cell line NSC-34 to ask the question: Do extracellular vesicles from muscle influence cell survival and/or neurite outgrowth of motor neurons? Conclusion: Our results show striking effects of extracellular vesicles derived from the muscle cell line on the motor neuron cell line in terms of neurite outgrowth and survival.

  7. Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34).

    Science.gov (United States)

    Madison, Roger D; McGee, Christopher; Rawson, Renee; Robinson, Grant A

    2014-01-01

    There is renewed interest in extracellular vesicles over the past decade or 2 after initially being thought of as simple cellular garbage cans to rid cells of unwanted components. Although there has been intense research into the role of extracellular vesicles in the fields of tumour and stem cell biology, the possible role of extracellular vesicles in nerve regeneration is just in its infancy. When a peripheral nerve is damaged, the communication between spinal cord motor neurons and their target muscles is disrupted and the result can be the loss of coordinated muscle movement. Despite state-of-the-art surgical procedures only approximately 10% of adults will recover full function after peripheral nerve repair. To improve upon such results will require a better understanding of the basic mechanisms that influence axon outgrowth and the interplay between the parent motor neuron and the distal end organ of muscle. It has previously been shown that extracellular vesicles are immunologically tolerated, display targeting ligands on their surface, and can be delivered in vivo to selected cell populations. All of these characteristics suggest that extracellular vesicles could play a significant role in nerve regeneration. We have carried out studies using 2 very well characterized cell lines, the C2C12 muscle cell line and the motor neuron cell line NSC-34 to ask the question: Do extracellular vesicles from muscle influence cell survival and/or neurite outgrowth of motor neurons? Our results show striking effects of extracellular vesicles derived from the muscle cell line on the motor neuron cell line in terms of neurite outgrowth and survival.

  8. Survival and growth of neurons with enkephalin-like immunoreactivity in fetal brain areas grafted to the anterior chamber of the eye.

    Science.gov (United States)

    Björklund, H; Hoffer, B J; Palmer, M R; Seiger, A; Olson, L

    1983-12-01

    Areas of fetal rat brain and spinal cord known to contain enkephalin-like immunoreactive cell bodies and/or terminal fields were transplanted to the anterior chamber of the eye of adult rats. Enkephalin-like immunoreactive neurons survive and produce an enkephalin-like immunoreactive fiber network within grafts of spinal cord, ventral medulla oblongata, ventrolateral pons, tectum, locus coeruleus, substantia nigra and the areas containing columna fornicis and globus pallidus. Although single intraocular grafts of neocortex do not apparently contain enkephalin-like immunoreactive fibers, such grafts contain a variable amount of sparsely distributed enkephalin-like fibers when sequentially grafted in oculo with either locus coeruleus or spinal cord. Combinations of locus coeruleus and globus pallidus contained a rich enkephalin fiber network in the locus coeruleus part and a sparse innervation of the globus pallidus part. We conclude that enkephalin-like immunoreactive neurons in small areas of fetal rat brain can be successfully transplanted to the anterior chamber of the eye. They are able to survive and develop to maturity in complete isolation from the rest of the brain. In general, the enkephalin-like immunoreactive fiber density in the various single grafts approximated that of their brain counterparts in situ. Fiber formation can be reinitiated in mature enkephalin-like immunoreactive neurons by addition of new brain target areas. Thus, the technique permits establishment of isolated, defined enkephalin systems and pathways accessible to functional analysis.

  9. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice.

    Science.gov (United States)

    Hong, Zhen-Yi; Yu, Shuang-Shuang; Wang, Zhi-Jun; Zhu, Yi-Zhun

    2015-08-07

    SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  10. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Zhen-Yi Hong

    2015-08-01

    Full Text Available SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson’s disease and Alzheimer’s disease (AD. In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1 double-transgenic mice without affecting amyloid-β (Aβ burden. In addition, decreases in cAMP-response element-binding protein (CREB phosphorylation, brain-derived neurotrophic factor (BDNF and tropomyosin-related kinase B (TrkB phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  11. Extension of the biotic ligand model of acute toxicity to a physiologically-based model of the survival time of rainbow trout (Oncorhynchus mykiss) exposed to silver.

    Science.gov (United States)

    Paquin, Paul R; Zoltay, Viktoria; Winfield, Richard P; Wu, Kuen Benjamin; Mathew, Rooni; Santore, Robert C; Di Toro, Dominic M

    2002-09-01

    Chemical speciation controls the bioavailability and toxicity of metals in aquatic systems and regulatory agencies are recognizing this as they develop updated water quality criteria (WQC) for metals. The factors that affect bioavailability may be quantitatively evaluated with the biotic ligand model (BLM). Within the context of the BLM framework, the 'biotic ligand' is the site where metal binding results in the manifestation of a toxic effect. While the BLM does account for the speciation and complexation of dissolved metal in solution, and competition among the free metal ion and other cations for binding sites at the biotic ligand, it does not explicitly consider either the physiological effects of metals on aquatic organisms, or the direct effect of water chemistry parameters such as pH, Ca(2+)and Na(+) on the physiological state of the organism. Here, a physiologically-based model of survival time is described. In addition to incorporating the effects of water chemistry on metal availability to the organism, via the BLM, it also considers the interaction of water chemistry on the physiological condition of the organism, independent of its effect on metal availability. At the same time it explicitly considers the degree of interaction of these factors with the organism and how this affects the rate at which cumulative damage occurs. An example application of the model to toxicity data for rainbow trout exposed to silver is presented to illustrate how this framework may be used to predict survival time for alternative exposure durations. The sodium balance model (SBM) that is described herein, a specific application of a more generic ion balance model (IBM) framework, adds a new physiological dimension to the previously developed BLM. As such it also necessarily adds another layer of complexity to this already useful predictive framework. While the demonstrated capability of the SBM to predict effects in relation to exposure duration is a useful feature of this

  12. Critical role of astrocytic interleukin-17 A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice

    Science.gov (United States)

    Lin, Y; Zhang, J-C; Yao, C-Y; Wu, Y; Abdelgawad, A F; Yao, S-L; Yuan, S-Y

    2016-01-01

    The brain and the immune system interact in complex ways after ischemic stroke, and the long-term effects of immune response associated with stroke remain controversial. As a linkage between innate and adaptive immunity, interleukin-17 A (IL-17 A) secreted from gamma delta (γδ) T cells has detrimental roles in the pathogenesis of acute ischemic stroke. However, to date, the long-term actions of IL-17 A after stroke have not been investigated. Here, we found that IL-17 A showed two distinct peaks of expression in the ischemic hemisphere: the first occurring within 3 days and the second on day 28 after stroke. Our data also showed that astrocyte was the major cellular source of IL-17 A that maintained and augmented subventricular zone (SVZ) neural precursor cells (NPCs) survival, neuronal differentiation, and subsequent synaptogenesis and functional recovery after stroke. IL-17 A also promoted neuronal differentiation in cultured NPCs from the ischemic SVZ. Furthermore, our in vitro data revealed that in primary astrocyte cultures activated astrocytes released IL-17 A via p38 mitogen-activated protein kinase (MAPK). Culture media from reactive astrocytes increased neuronal differentiation of NSCs in vitro. Blockade of IL-17 A with neutralizing antibody prevented this effect. In addition, after screening for multiple signaling pathways, we revealed that the p38 MAPK/calpain 1 signaling pathway was involved in IL-17 A-mediated neurogenesis in vivo and in vitro. Thus, our results reveal a previously uncharacterized property of astrocytic IL-17 A in the maintenance and augment of survival and neuronal differentiation of NPCs, and subsequent synaptogenesis and spontaneous recovery after ischemic stroke. PMID:27336717

  13. Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus.

    Directory of Open Access Journals (Sweden)

    Natalie J Groves

    Full Text Available Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD deficiency in BALB/c mice was associated with (a adult hippocampal neurogenesis at baseline, b following 6 weeks of voluntary wheel running and (c a depressive-like phenotype on the forced swim test (FST, which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX, and incorporation of 5-Bromo-2'-Deoxyuridine (BrdU within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.

  14. Expression of exogenous LIN28 contributes to proliferation and survival of mouse primary cortical neurons in vitro.

    Science.gov (United States)

    Bhuiyan, M I H; Lee, J-H; Kim, S Y; Cho, K-O

    2013-09-17

    LIN28, an RNA-binding protein, is known to be involved in the regulation of many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. In this study, we investigated the effect of constitutively expressing exogenous LIN28 on neuronal cell proliferation and viability in vitro. Plasmids containing LIN28-green fluorescent protein (GFP) or GFP were introduced into the embryonic mouse brains at E14.5 by in utero electroporation. Two days after electroporation, embryonic cortices were harvested and cultured. It was found that transfected cells stably overexpressed LIN28 in vitro. Viability curve from live cell imaging showed that the number of GFP-expressing cells decreased over time in line with naive primary cortical neurons. In contrast, the number of LIN28-GFP-overexpressing neurons initially increased and remained high at later time-points in culture than GFP-expressing cells. Double immunofluorescence showed that at an early time in culture, the number of Ki-67/GFP double-positive cells was higher in the LIN28-GFP group than that of controls. Moreover, there were significantly lower numbers of condensed nuclei/GFP- and cleaved caspase-3/GFP-positive cells in the LIN28-GFP groups compared to control GFP. Furthermore, it was confirmed that the LIN28-GFP-expressing cells at days in vitro (DIV)13 were neuronal nuclei (NeuN)-positive mature neurons. Finally, the expression of insulin-like growth factor 2 (IGF-2) was induced in LIN28-expressing primary cortical neurons, which was not detected in controls. Taken together, our results indicate that the expression of exogenous LIN28 can promote the proliferation of neural progenitor cells and exert prosurvival effect on primary cortical neurons by inhibiting caspase-dependent apoptosis, possibly via upregulation of IGF-2. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Systemic administration of valproic acid and zonisamide promotes the survival and differentiation of induced pluripotent stem cell–derived dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    Tatsuya eYoshikawa

    2013-02-01

    Full Text Available Cell replacement therapy using embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs is a promising strategy for the treatment of neurologic diseases such as Parkinson’s disease (PD. However, a limiting factor for effective cell transplantation is the low survival rate of grafted cells, especially neurons. In this study, we modified the host environment and investigated whether the simultaneous administration of soluble factors can improve the survival and differentiation of murine iPSC-derived dopaminergic (DA neurons in host brains. With the goal of applying this technology in clinical settings in the near future, we selected drugs that were already approved for clinical use. The drugs included two commonly used anticonvulsants, valproic acid (VPA and zonisamide (ZNS, and estradiol (E2, also known as biologically active estrogen. Following neural induction of murine iPSCs, we collected neural progenitor cells by sorting PSA-NCAM+ cells, then treated the PSA-NCAM+ cells with drugs for four days. An immunofluorescence study revealed that 0.01 mM and 0.1 mM of VPA and 10 nM of E2 increased the percentage of tyrosine hydroxylase+ (TH: a DA neuron marker cells in vitro. Furthermore, 0.1 mM of VPA increased the percentage of TH+ cells that simultaneously express the midbrain markers FOXA2 and NURR1. Next, in order to determine the effects of the drugs in vivo, the iPSC-derived NPCs were transplanted into the striata of intact SD rats. The animals received intraperitoneal injections of one of the drugs for four weeks, then were subjected to an immunofluorescence study. VPA administration (150 mg/kg/daily increased the number of NeuN+ postmitotic neurons and TH+ DA neurons in the grafts. Furthermore, VPA (150 mg/kg/daily and ZNS (30 mg/kg/daily increased the number of TH+FOXA2+ midbrain DA neurons. These results suggest that the systemic administration of VPA and ZNS may improve the efficiency of cell replacement therapy using i

  16. Increasing levels of wild-type CREB up-regulates several activity-regulated inhibitor of death (AID genes and promotes neuronal survival

    Directory of Open Access Journals (Sweden)

    Tan Yan-Wei

    2012-05-01

    Full Text Available Abstract Background CREB (cAMP-response element binding protein is the prototypical signal-regulated transcription factor. In neurons, it is the target of the synaptic activity-induced nuclear calcium-calcium/calmodulin dependent protein kinase (CaMK IV signaling pathway that controls the expression of genes important for acquired neuroprotection as well as other long-lasting adaptive processes in the nervous system. The function of CREB as a transcriptional activator is controlled by its phosphorylation on serine 133, which can be catalyzed by CaMKIV and leads to the recruitment of the co-activator, CREB binding protein (CBP. Activation of CBP function by nuclear calcium-CaMKIV signaling is a second regulatory step required for CREB/CBP-mediated transcription. Results Here we used recombinant adeno-associated virus (rAAV to increase the levels of wild type CREB or to overexpress a mutant version of CREB (mCREB containing a serine to alanine mutation at position amino acid 133 in mouse hippocampal neurons. Increasing the levels of CREB was sufficient to boost neuroprotective activity even under basal conditions (i.e., in the absence of stimulation of synaptic activity. In contrast, overexpression of mCREB increased cell death. The ratio of phospho(serine 133CREB to CREB immunoreactivity in unstimulated hippocampal neurons was similar for endogenous CREB and overexpressed wild type CREB and, as expected, dramatically reduced for overexpressed mCREB. A gene expression analysis revealed that increased expression of CREB but not that of mCREB in hippocampal neurons led to elevated expression levels of bdnf as well as that of several members of a previously characterized set of Activity-regulated Inhibitor of Death (AID genes, which include atf3, btg2, gadd45β, and gadd45γ. Conclusions Our findings indicate that the expression levels of wild type CREB are a critical determinant of the ability of hippocampal neurons to survive harmful conditions

  17. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin V

    2003-01-01

    that phosphatidylinositol 3-kinase (PI3K) is required for NCAM-mediated neurite outgrowth from PC12-E2 cells and from cerebellar and dopaminergic neurones in primary culture, and that the thr/ser kinase Akt/protein kinase B (PKB) is phosphorylated downstream of PI3K after stimulation with C3. Moreover, we present data...... to be dependent on PI3K.......The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein...

  18. In Vitro Modulation of TrkB Receptor Signaling upon Sequential Delivery of Curcumin-DHA Loaded Carriers Towards Promoting Neuronal Survival.

    Science.gov (United States)

    Guerzoni, Luis P B; Nicolas, Valérie; Angelova, Angelina

    2017-02-01

    To in vitro investigate the capacity of carrier-free and lipid-nanoparticle (NP)-encapsulated phytochemical compounds to prevent neuronal damage through neurotrophin potentiating activities. Delivery of molecules promoting the neurotrophin receptor signaling in the central nervous system (CNS) present ongoing interest for combination therapy development. Super-resolution Stimulated Emission Depletion (STED) microscopy imaging and flow cytometry analysis were employed to study the expression of the neurotrophin TrkB receptor in a neuronal cell model, which is highly responsive to binding of brain-derived neurotrophic factor (BDNF). Dual drug-loaded nanoparticle formulations, prepared by self-assembly of lyotropic lipids and PEGylated amphiphile derivatives, were delivered to differentiated human neuroblastoma SH-SY5Y cells subjected to degenerative conditions. The expression of BDNF in the intra and extracellular domains was quantified by ELISA and flow cytometry after sequential treatment of the degenerating SH-SY5Y cells by neurotherapeutic formulations. Flow cytometry was also used to assess the phosphorylation of the transcription factor cAMP response element-binding protein (CREB) in the intracellular domain as a result of the treatment by nanoformulations. Over time, dual drug formulations (curcumin and docosahexaenoic acid (DHA)) promoted the neuronal survival and repair processes through enhanced BDNF secretion and increased phosphorylation of CREB as compared to untreated degenerating cells.

  19. Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats.

    Science.gov (United States)

    Cao, Jia-Yu; Lin, Yong; Han, Yan-Fei; Ding, Sheng-Hao; Fan, Yi-Ling; Pan, Yao-Hua; Zhao, Bing; Guo, Qin-Hua; Sun, Wen-Hua; Wan, Jie-Qing; Tong, Xiao-Ping

    2018-02-06

    Nerve growth factor (NGF) has been reported to prevent neuronal damage and contributes to the functional recovery in animal brain injury models and human ischemic disease as well. We aimed to investigate a potential therapeutic effect of NGF gene treatment in ischemic stroke and to estimate the functional recovery both at the cellular and cognitive levels in an ischemia rat model. After microinjection of pseudolentivirus-delivered β-NGF into an established ischemic stroke model in rats (tMCAO), we estimated neuronal cell apoptosis with TUNEL labeling and neurogenesis by cell proliferation marker Ki67 staining in both ischemic core and penumbra of striatum. Furthermore, we used behavioral functional tests, Morris water maze performance, to evaluate cognitive functional recovery in vivo and propose a potential underlying mechanism. We found that pseudolentivirus-mediated delivery of β-NGF gene into the brain induced high expression in striatum of the infarct core area after ischemia in rats. The β-NGF overexpression in the striatal infarction core after ischemia not only improved neuronal survival by reducing cell apoptosis and increasing cell proliferation, but also rescued cognitive functional impairment through upregulation of GAP-43 protein expression in tMCAO rat model of ischemia. This study demonstrates a potential β-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients. © 2018 John Wiley & Sons Ltd.

  20. Resistance of subventricular neural stem cells to chronic hypoxemia despite structural disorganization of the germinal center and impairment of neuronal and oligodendrocyte survival

    Science.gov (United States)

    d’Anglemont de Tassigny, Xavier; Sirerol-Piquer, M Salomé; Gómez-Pinedo, Ulises; Pardal, Ricardo; Bonilla, Sonia; Capilla-Gonzalez, Vivian; López-López, Ivette; De la Torre-Laviana, Francisco Javier; García-Verdugo, José Manuel; López-Barneo, José

    2015-01-01

    Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone) characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These findings help explain the effects of hypoxia on adult neurogenesis and provide new perspectives on brain responsiveness to persistent hypoxemia. PMID:27774479

  1. Systemic Administration of Mesenchymal Stem Cells Increases Neuron Survival after Global Cerebral Ischemia In Vivo (2VO

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    Luisa Perasso

    2010-01-01

    Full Text Available Although many studies have shown that administration of stem cells after focal cerebral ischemia improves brain damage, very little data are available concerning the damage induced by global cerebral ischemia. The latter causes neuronal death in selectively vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats transient global ischemia was induced using bilateral common carotid artery occlusion for 20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to investigate histological damage. MSC did not fully protect against ischemic damage, as the number of viable neurons in this group was lower than in normal (sham-operated rats. However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally higher than in rats that had been subjected to ischemia but not treated with MSC. We conclude that intravenous administration of MSC after transient global ischemia reduces hippocampal damage.

  2. Does the survival motor neuron copy number variation play a role in the onset and severity of sporadic amyotrophic lateral sclerosis in Malians?

    Science.gov (United States)

    Sangare, Modibo; Dicko, Ilo; Guinto, Cheick Oumar; Sissoko, Adama; Dembele, Kekouta; Coulibaly, Youlouza; Coulibaly, Siaka Y; Landoure, Guida; Diallo, Abdallah; Dolo, Mamadou; Dolo, Housseini; Maiga, Boubacar; Traore, Moussa; Karembe, Mamadou; Traore, Kadiatou; Toure, Amadou; Sylla, Mariam; Togora, Arouna; Coulibaly, Souleymane; Traore, Sékou Fantamady; Hendrickson, Brant; Bricceno, Katherine; Schindler, Alice B; Kokkinis, Angela; Meilleur, Katherine G; Sangho, Hammadoun Ali; Diakite, Brehima; Kassogue, Yaya; Coulibaly, Yaya Ibrahim; Burnett, Barrington; Maiga, Youssoufa; Doumbia, Seydou; Fischbeck, Kenneth H

    2016-06-01

    Spinal muscular atrophy (SMA) and sporadic amyotrophic lateral sclerosis (SALS) are both motor neuron disorders. SMA results from the deletion of the survival motor neuron ( SMN ) 1 gene. High or low SMN1 copy number and the absence of SMN2 have been reported as risk factors for the development or severity of SALS. To investigate the role of SMN gene copy number in the onset and severity of SALS in Malians. We determined the SMN1 and SMN2 copy number in genomic DNA samples from 391 Malian adult volunteers, 120 Yoruba from Nigeria, 120 Luyha from Kenya and 74 U.S. Caucasians using a Taqman quantitative PCR assay. We evaluated the SALS risk based on the estimated SMA protein level using the Veldink formula ( SMN1 copy number + 0.2 ∗  SMN2 copy number). We also characterized the disease natural history in 15 ALS patients at the teaching hospital of Point G, Bamako, Mali. We found that 131 of 391 (33.5%) had an estimated SMN protein expression of ≤ 2.2; 60 out of 391 (15.3%) had an estimated SMN protein expression < 2 and would be at risk of ALS and the disease onset was as early as 16 years old. All 15 patients were male and some were physically handicapped within 1-2 years in the disease course. Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.

  3. Resistance of subventricular neural stem cells to chronic hypoxemia despite structural disorganization of the germinal center and impairment of neuronal and oligodendrocyte survival

    Directory of Open Access Journals (Sweden)

    d’Anglemont de Tassigny X

    2015-06-01

    Full Text Available Xavier d'Anglemont de Tassigny,1,* M Salomé Sirerol-Piquer,2,3,* Ulises Gómez-Pinedo,4 Ricardo Pardal,1 Sonia Bonilla,1 Vivian Capilla-Gonzalez,2 Ivette López-López,1 Francisco Javier De la Torre-Laviana,1 José Manuel García-Verdugo,2,3 José López-Barneo1,3 1Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain; 2Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain; 3Network Center of Biomedical Research on Neurodegenerative Diseases (CIBERNED, Spain; 4Laboratory of Regenerative Medicine, San Carlos Institute of Health Investigation, Madrid, Spain *These authors contributed equally to this work Abstract: Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These

  4. Silver Nanoparticles

    Science.gov (United States)

    Khaydarov, R. R.; Khaydarov, R. A.; Estrin, Y.; Evgrafova, S.; Scheper, T.; Endres, C.; Cho, S. Y.

    The bactericidal effect of silver nanoparticles obtained by a novel electrochemical method on Escherichia coli, Staphylococcus aureus, Aspergillus niger and Penicillium phoeniceum cultures has been studied. The tests conducted have demonstrated that synthesized silver nanoparticles — when added to water paints or cotton fabrics — show a pronounced antibacterial/antifungal effect. It was shown that smaller silver nanoparticles have a greater antibacterial/antifungal efficacy. The paper also provides a review of scientific literature with regard to recent developments in the field of toxicity of silver nanoparticles and its effect on environment and human health.

  5. Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

    Science.gov (United States)

    Kuo, Yung-Chih; Lin, Che-Yu; Li, Jay-Shake; Lou, Yung-I

    2017-01-01

    Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer’s disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood–brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD. PMID:28280340

  6. Inactivation of glycogen synthase kinase-3beta and up-regulation of LINGO-1 are involved in LINGO-1 antagonist regulated survival of cerebellar granular neurons.

    Science.gov (United States)

    Zhao, Xiang-Hui; Jin, Wei-Lin; Wu, Jiang; Mi, Sha; Ju, Gong

    2008-08-01

    LINGO-1 has been critically implicated in the central regulation of CNS axon regeneration and oligodendrocyte maturation. We have recently demonstrated that pretreatment with LINGO-1 antagonist (LINGO-1-Fc) inhibited low potassium-induced cerebellar granular neurons (CGNs) apoptosis. In the present study, we examined the neuroprotective mechanism of LINGO-1-Fc by Western blot and in situ GST pull-down assay. CGN cultures were preincubated in medium with LINGO-1-Fc or control protein at the concentration of 10 mug/ml for 2 h and then switched to low potassium medium in the presence of corresponding proteins. Cultures were harvested at indicated time intervals for successive analysis. Several apoptosis-associated signaling factors, GSK-3beta, ERK1/2, and Rho GTPases, were observed to be activated in response to potassium deprivation and the activation/dephosphorylation of GSK-3beta was suppressed by LINGO-1-Fc pretreatment compared with control group. Besides, the endogenous LINGO-1 expression level of CGN cultures was augmented by low potassium stimuli and restrained by LINGO-1 antagonist treatment. Although the protein level of p75(NTR) and Nogo-A were down-regulated in different patterns during apoptosis, neither of them was affected by LINGO-1-Fc application. Taken together, these results suggest a new mechanism of LINGO-1 antagonist regulated neuronal survival involving protein synthesis of LINGO-1 and inactivation of GSK-3 pathway.

  7. The sirtuin inhibitor nicotinamide enhances neuronal cell survival during acute anoxic injury through AKT, BAD, PARP, and mitochondrial associated "anti-apoptotic" pathways.

    Science.gov (United States)

    Chong, Zhao-Zhong; Lin, Shi-Hua; Li, Faqi; Maiese, Kenneth

    2005-10-01

    Understanding the role of nicotinamide (NIC) in different cell systems represents a significant challenge in several respects. Recently, NIC has been reported to have diverse roles during cell biology. In the absence of NIC, sirtuin protein activity is enhanced and pyrazinamidase/nicotinamidase 1 (PNC1) expression, an enzyme that deaminates NIC to convert NIC into nicotinic acid, is increased to lead to lifespan extension during calorie restriction, at least in yeast. Yet, NIC may be critical for cell survival as well as the modulation of inflammatory injury during both experimental models as well as in clinical studies. We therefore investigated some of the underlying signal transduction pathways that could be critical for the determination of the neuroprotective properties of NIC. We examined neuronal injury by trypan blue exclusion, DNA fragmentation, phosphatidylserine (PS) exposure, Akt1 phosphorylation, Bad phosphorylation, mitochondrial membrane potential, caspase activity, cleavage of poly(ADP-ribose) polymerase (PARP), and mitogen-activated protein kinases (MAPKs) phosphorylation. Application of NIC (12.5 mM) significantly increased neuronal survival from 38 -/+ 3% of anoxia treated alone to 68 +/- 3%, decreased DNA fragmentation and membrane PS exposure from 67 -/+ 4% and 61 -/+ 5% of anoxia treated alone to 30 +/- 4% and 26 +/- 4% respectively. We further demonstrate that NIC functions through Akt1 activation, Bad phosphorylation, and the downstream modulation of mitochrondrial membrane potential, cytochrome c release, caspase 1, 3, and 8 - like activities, and PARP integrity to prevent genomic DNA degradation and PS externalization during anoxia. Yet, NIC does not alter the activity of either the MAPKs p38 or JNK, suggesting that protection by NIC during anoxia is independent of the p38 and JNK pathways. Additional investigations targeted to elucidate the cellular pathways responsible for the ability of NIC to modulate both lifespan extension and

  8. Mouse survival motor neuron alleles that mimic SMN2 splicing and are inducible rescue embryonic lethality early in development but not late.

    Directory of Open Access Journals (Sweden)

    Suzan M Hammond

    Full Text Available Spinal muscular atrophy (SMA is caused by low survival motor neuron (SMN levels and patients represent a clinical spectrum due primarily to varying copies of the survival motor neuron-2 (SMN2 gene. Patient and animals studies show that disease severity is abrogated as SMN levels increase. Since therapies currently being pursued target the induction of SMN, it will be important to understand the dosage, timing and cellular requirements of SMN for disease etiology and potential therapeutic intervention. This requires new mouse models that can induce SMN temporally and/or spatially. Here we describe the generation of two hypomorphic Smn alleles, Smn(C-T-Neo and Smn(2B-Neo. These alleles mimic SMN2 exon 7 splicing, titre Smn levels and are inducible. They were specifically designed so that up to three independent lines of mice could be generated, herein we describe two. In a homozygous state each allele results in embryonic lethality. Analysis of these mutants indicates that greater than 5% of Smn protein is required for normal development. The severe hypomorphic nature of these alleles is caused by inclusion of a loxP-flanked neomycin gene selection cassette in Smn intron 7, which can be removed with Cre recombinase. In vitro and in vivo experiments demonstrate these as inducible Smn alleles. When combined with an inducible Cre mouse, embryonic lethality caused by low Smn levels can be rescued early in gestation but not late. This provides direct genetic evidence that a therapeutic window for SMN inductive therapies may exist. Importantly, these lines fill a void for inducible Smn alleles. They also provide a base from which to generate a large repertoire of SMA models of varying disease severities when combined with other Smn alleles or SMN2-containing mice.

  9. Exposure to extremely low frequency (50 Hz electromagnetic field changes the survival rate and morphometric characteristics of neurosecretory neurons of the earthworm Eisenia foetida (Oligochaeta under illumination stress

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    Banovački Zorana

    2013-01-01

    Full Text Available An in vivo model was set up to establish the behavioral stress response (rate of survival and morphometric characteristics of A1 protocerebral neurosecretory neurons (cell size of Eisenia foetida (Oligochaeta as a result of the synergetic effect of extremely low frequency electromagnetic fields (ELF-EMF - 50 Hz, 50 μT, 17 V/m and 50 Hz, 150 μT, 17 V/m, respectively and constant illumination (420-450 lux. If combined, these two stressors significantly (p<0.05 increased the survival rate of E. foetida in the 150 μT-exposed animals, because of delayed caudal autotomy reflex, an indicator of stress response. In addition, morphometric analysis indicated that there were changes in the protocerebral neurosecretory cells after exposure to the ELF-EMF. The present data support the view that short-term ELF-EMF exposure in “windows” of intensity is likely to stimulate the immune and neuroendocrine response of E. foetida.

  10. The tyrosine kinase receptor Tyro3 enhances lifespan and neuropeptide Y (Npy neuron survival in the mouse anorexia (anx mutation

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    Dennis Y. Kim

    2017-05-01

    Full Text Available Severe appetite and weight loss define the eating disorder anorexia nervosa, and can also accompany the progression of some neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS. Although acute loss of hypothalamic neurons that produce appetite-stimulating neuropeptide Y (Npy and agouti-related peptide (Agrp in adult mice or in mice homozygous for the anorexia (anx mutation causes aphagia, our understanding of the factors that help maintain appetite regulatory circuitry is limited. Here we identify a mutation (C19T that converts an arginine to a tryptophan (R7W in the TYRO3 protein tyrosine kinase 3 (Tyro3 gene, which resides within the anx critical interval, as contributing to the severity of anx phenotypes. Our observation that, like Tyro3−/− mice, anx/anx mice exhibit abnormal secondary platelet aggregation suggested that the C19T Tyro3 variant might have functional consequences. Tyro3 is expressed in the hypothalamus and other brain regions affected by the anx mutation, and its mRNA localization appeared abnormal in anx/anx brains by postnatal day 19 (P19. The presence of wild-type Tyro3 transgenes, but not an R7W-Tyro3 transgene, doubled the weight and lifespans of anx/anx mice and near-normal numbers of hypothalamic Npy-expressing neurons were present in Tyro3-transgenic anx/anx mice at P19. Although no differences in R7W-Tyro3 signal sequence function or protein localization were discernible in vitro, distribution of R7W-Tyro3 protein differed from that of Tyro3 protein in the cerebellum of transgenic wild-type mice. Thus, R7W-Tyro3 protein localization deficits are only detectable in vivo. Further analyses revealed that the C19T Tyro3 mutation is present in a few other mouse strains, and hence is not the causative anx mutation, but rather an anx modifier. Our work shows that Tyro3 has prosurvival roles in the appetite regulatory circuitry and could also provide useful insights towards the development of interventions

  11. Survival of Cochlear Spiral Ganglion Neurons Improved In vivo by Anti-miR204 via TMPRSS3.

    Science.gov (United States)

    Peng, A; Li, Y; Pan, X; Ge, S; Wang, Q; Li, S; Zhu, G; Liu, J

    2015-05-08

    Sensorineural hearing loss (SNHL) is caused by damage to hair cells followed by degeneration of the spiral ganglion neurons (SGNs), and cochlear implanting is an effective treatment. Unfortunately, the progressive hearing loss is still found due to ongoing degeneration of cochlear SGNs. The aim of this study was to investigate the neuroprotective effect of anti-miR204 on SGNs in vivo. Our recent in vitro work suggested that anti-miR204 could be a potential therapeutic strategy in SNHL via rescue cochlear SGNs. In order to further our knowledge of miR204 on SGNs in vivo, we made a kanamycin ototoxicity model and then virus containing the anti-miR204 gene (AAV1-anti-miR204) was microinjected into the cochlear of the model to monitor the effect. The SGNs were rescued by anti-miR204 in the kanamycin ototoxicity mouse group compared to the sham group. Moreover, expression of TMPRSS3 in SGNs was saved by anti-miR204 treatment. Anti-miR204 might be an alternate way to alleviate the degeneration of cochlear SGNs of kanamycin ototoxicity mice.

  12. Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning.

    Science.gov (United States)

    Inta, Dragos; Lang, Undine E; Borgwardt, Stefan; Meyer-Lindenberg, Andreas; Gass, Peter

    2017-05-01

    The implication of neuroinflammation in schizophrenia, sustained by recent genetic evidence, represents one of the most exciting topics in schizophrenia research. Drugs which inhibit microglia activation, especially the classical tetracycline antibiotic minocycline are currently under investigation as alternative antipsychotics. However, recent studies demonstrated that microglia activation is not only a hallmark of neuroinflammation, but plays important roles during brain development. Inhibition of microglia activation by minocycline was shown to induce extensive neuronal cell death and to impair subventricular zone (SVZ) neurogenesis and synaptic pruning in the early postnatal and adolescent rodent brain, respectively. These deleterious effects contrast with the neuroprotective actions of minocycline at adult stages. They are of potential importance for schizophrenia, since minocycline triggers similar pro-apoptotic effects in the developing brain as NMDA receptor (NMDAR) antagonists, known to induce long-term schizophrenia-like abnormalities. Moreover, altered postnatal neurogenesis, recently described in the human striatum, was proposed to induce striatal dopamine dysregulation associated with schizophrenia. Finally, the effect of minocycline on synapse remodeling is of interest considering the recently reported strong genetic association of the pruning-regulating complement factor gene C4A with schizophrenia. This raises the exciting possibility that in conditions of hyperactive synaptic pruning, as supposed in schizophrenia, the inhibitory action of minocycline turns into a beneficial effect, with relevance for early therapeutic interventions. Altogether, these data support a differential view on microglia activation and its inhibition. Further studies are needed to clarify the relevance of these results for the pathogenesis of schizophrenia and the use of minocycline as antipsychotic drug. © The Author 2016. Published by Oxford University Press on behalf of

  13. Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation.

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    Marc P Forrest

    Full Text Available Haploinsufficiency of TCF4 causes Pitt-Hopkins syndrome (PTHS: a severe form of mental retardation with phenotypic similarities to Angelman, Mowat-Wilson and Rett syndromes. Genome-wide association studies have also found that common variants in TCF4 are associated with an increased risk of schizophrenia. Although TCF4 is transcription factor, little is known about TCF4-regulated processes in the brain. In this study we used genome-wide expression profiling to determine the effects of acute TCF4 knockdown on gene expression in SH-SY5Y neuroblastoma cells. We identified 1204 gene expression changes (494 upregulated, 710 downregulated in TCF4 knockdown cells. Pathway and enrichment analysis on the differentially expressed genes in TCF4-knockdown cells identified an over-representation of genes involved in TGF-β signaling, epithelial to mesenchymal transition (EMT and apoptosis. Among the most significantly differentially expressed genes were the EMT regulators, SNAI2 and DEC1 and the proneural genes, NEUROG2 and ASCL1. Altered expression of several mental retardation genes such as UBE3A (Angelman Syndrome, ZEB2 (Mowat-Wilson Syndrome and MEF2C was also found in TCF4-depleted cells. These data suggest that TCF4 regulates a number of convergent signaling pathways involved in cell differentiation and survival in addition to a subset of clinically important mental retardation genes.

  14. HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation.

    Science.gov (United States)

    Hao le, Thi; Duy, Phan Q; An, Min; Talbot, Jared; Iyer, Chitra C; Wolman, Marc; Beattie, Christine E

    2017-11-29

    Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43, is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA.SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding

  15. A Drosophila Model of Spinal Muscular Atrophy Uncouples snRNP Biogenesis Functions of Survival Motor Neuron from Locomotion and Viability Defects

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    Kavita Praveen

    2012-06-01

    Full Text Available The spinal muscular atrophy (SMA protein, survival motor neuron (SMN, functions in the biogenesis of small nuclear ribonucleoproteins (snRNPs. SMN has also been implicated in tissue-specific functions; however, it remains unclear which of these is important for the etiology of SMA. Smn null mutants display larval lethality and show significant locomotion defects as well as reductions in minor-class spliceosomal snRNAs. Despite these reductions, we found no appreciable defects in the splicing of mRNAs containing minor-class introns. Transgenic expression of low levels of either wild-type or an SMA patient-derived form of SMN rescued the larval lethality and locomotor defects; however, snRNA levels were not restored. Thus, the snRNP biogenesis function of SMN is not a major contributor to the phenotype of Smn null mutants. These findings have major implications for SMA etiology because they show that SMN's role in snRNP biogenesis can be uncoupled from the organismal viability and locomotor defects.

  16. Dephosphorylation of survival motor neurons (SMN) by PPM1G/PP2Cγ governs Cajal body localization and stability of the SMN complex

    Science.gov (United States)

    Petri, Sebastian; Grimmler, Matthias; Over, Sabine; Fischer, Utz; Gruss, Oliver J.

    2007-01-01

    The survival motor neuron (SMN) complex functions in maturation of uridine-rich small nuclear ribonucleoprotein (RNP) particles. SMN mediates the cytoplasmic assembly of Sm proteins onto uridine-rich small RNAs, and then participates in targeting RNPs to nuclear Cajal bodies (CBs). Recent studies have suggested that phosphorylation might control localization and function of the SMN complex. Here, we show that the nuclear phosphatase PPM1G/PP2Cγ interacts with and dephosphorylates the SMN complex. Small interfering RNA knockdown of PPM1G leads to an altered phosphorylation pattern of SMN and Gemin3, loss of SMN from CBs, and reduced stability of SMN. Accumulation in CBs is restored upon overexpression of catalytically active, but not that of inactive, PPM1G. This demonstrates that PPM1G's phosphatase activity is necessary to maintain SMN subcellular distribution. Concomitant knockdown of unr interacting protein (unrip), a component implicated in cytoplasmic retention of the SMN complex, also rescues the localization defects. Our data suggest that an interplay between PPM1G and unrip determine compartment-specific phosphorylation patterns, localization, and function of the SMN complex. PMID:17984321

  17. Purple sweet potato color alleviates D-galactose-induced brain aging in old mice by promoting survival of neurons via PI3K pathway and inhibiting cytochrome C-mediated apoptosis.

    Science.gov (United States)

    Lu, Jun; Wu, Dong-mei; Zheng, Yuan-lin; Hu, Bin; Zhang, Zi-feng

    2010-05-01

    Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, protects brain function against oxidative stress induced by D-galactose (D-gal) (Sigma-Aldrich, St. Louis, MO, USA). Our data showed that PSPC enhanced open-field activity, decreased step-through latency, and improved spatial learning and memory ability in D-gal-treated old mice by decreasing advanced glycation end-products' (AGEs) formation and the AGE receptor (RAGE) expression, and by elevating Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (Sigma-Aldrich) and catalase (CAT) expression and activity. Cleavage of caspase-3 and increased terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated old mice were inhibited by PSPC, which might be attributed to its antioxidant property. PSPC also suppressed the activation of c-Jun NH(2)-terminal kinase (JNK) and the release of cytochrome c from mitochondria that counteracted the onset of neuronal apoptosis in D-gal-treated old mice. Furthermore, it was demonstrated that phosphoinositide 3-kinase (PI3K) activation was required for PSPC to promote the neuronal survival accompanied with phosphorylation and activation of Akt and p44/42 mitogen-activated protein kinase (MAPK) by using PI3K inhibitor LY294002 (Cell Signaling Technology, Inc., Beverly, MA, USA), implicating a neuronal survival mechanism. The present results suggest that neuronal survival promoted by PSPC may be a potentially effective method to enhance resistance of neurons to age-related disease.

  18. A peptide derived from the CD loop-D helix region of ciliary neurotrophic factor (CNTF) induces neuronal differentiation and survival by binding to the leukemia inhibitory factor (LIF) receptor and common cytokine receptor chain gp130

    DEFF Research Database (Denmark)

    Rathje, Mette; Pankratova, Stanislava; Nielsen, Janne

    2011-01-01

    Ciliary neurotrophic factor (CNTF) induces neuronal differentiation and promotes the survival of various neuronal cell types by binding to a receptor complex formed by CNTF receptor a (CNTFRa), gp130, and the leukemia inhibitory factor (LIF) receptor (LIFR). The CD loop-D helix region of CNTF has...... that these receptors are involved in the effects of cintrofin. The C-terminal part of the peptide, corresponding to the D helix region of CNTF, was shown to be essential for the neuritogenic action of the peptide. CNTF and LIF induced neurite outgrowth in CGNs plated on laminin-coated slides. On uncoated slides, CNTF...... similar to those induced by CNTF and may be a valuable survival agent with possible therapeutic potential....

  19. Russell-Silver syndrome

    Science.gov (United States)

    Silver-Russell syndrome; Silver syndrome; RSS; Russell-Silver syndrome ... One in 10 children with this syndrome has a problem involving chromosome 7. In other people with the syndrome, it may affect chromosome 11. Most of the time, it ...

  20. Laminin α5 substrates promote survival, network formation and functional development of human pluripotent stem cell-derived neurons in vitro.

    Science.gov (United States)

    Hyysalo, Anu; Ristola, Mervi; Mäkinen, Meeri E-L; Häyrynen, Sergei; Nykter, Matti; Narkilahti, Susanna

    2017-10-01

    Laminins are one of the major protein groups in the extracellular matrix (ECM) and specific laminin isoforms are crucial for neuronal functions in the central nervous system in vivo. In the present study, we compared recombinant human laminin isoforms (LN211, LN332, LN411, LN511, and LN521) and laminin isoform fragment (LN511-E8) in in vitro cultures of human pluripotent stem cell (hPSC)-derived neurons. We showed that laminin substrates containing the α5-chain are important for neuronal attachment, viability and network formation, as detected by phase contrast imaging, viability staining, and immunocytochemistry. Gene expression analysis showed that the molecular mechanisms involved in the preference of hPSC-derived neurons for specific laminin isoforms could be related to ECM remodeling and cell adhesion. Importantly, the microelectrode array analysis revealed the widest distribution of electrophysiologically active neurons on laminin α5 substrates, indicating most efficient development of neuronal network functionality. This study shows that specific laminin α5 substrates provide a controlled in vitro culture environment for hPSC-derived neurons. These substrates can be utilized not only to enhance the production of functional hPSC-derived neurons for in vitro applications like disease modeling, toxicological studies, and drug discovery, but also for the production of clinical grade hPSC-derived cells for regenerative medicine applications. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. The basic helix-loop-helix transcription factor Nex-1/Math-2 promotes neuronal survival of PC12 cells by modulating the dynamic expression of anti-apoptotic and cell cycle regulators.

    Science.gov (United States)

    Uittenbogaard, Martine; Chiaramello, Anne

    2005-02-01

    The basic helix-loop-helix transcription factor Nex1/Math-2 belongs to the NeuroD subfamily, which plays a critical role during neuronal differentiation and maintenance of the differentiated state. Previously, we demonstrated that Nex1 is a key regulatory component of the nerve growth factor (NGF) pathway. Further supporting this hypothesis, this study shows that Nex1 has survival-inducing properties similar to NGF, as Nex1-overexpressing PC12 cells survive in the absence of trophic factors. We dissected the molecular mechanism by which Nex1 confers neuroprotection upon serum removal and found that constitutive expression of Nex1 maintained the expression of specific G1 phase cyclin-dependent kinase inhibitors and concomitantly induced a dynamic expression profile of key anti-apoptotic regulators. This study provides the first evidence of the underlying mechanism by which a member of the NeuroD-subfamily promotes an active anti-apoptotic program essential to the survival of neurons. Our results suggest that the survival program may be viewed as an integral component of the intrinsic programming of the differentiated state.

  2. A peptide derived from the CD loop-D helix region of ciliary neurotrophic factor (CNTF) induces neuronal differentiation and survival by binding to the leukemia inhibitory factor (LIF) receptor and common cytokine receptor chain gp130.

    Science.gov (United States)

    Rathje, Mette; Pankratova, Stanislava; Nielsen, Janne; Gotfryd, Kamil; Bock, Elisabeth; Berezin, Vladimir

    2011-12-01

    Ciliary neurotrophic factor (CNTF) induces neuronal differentiation and promotes the survival of various neuronal cell types by binding to a receptor complex formed by CNTF receptor α (CNTFRα), gp130, and the leukemia inhibitory factor (LIF) receptor (LIFR). The CD loop-D helix region of CNTF has been suggested to be important for the cytokine interaction with LIFR. We designed a peptide, termed cintrofin, that encompasses this region. Surface plasmon resonance analysis demonstrated that cintrofin bound to LIFR and gp130, but not to CNTFRα, with apparent KD values of 35 nM and 1.1 nM, respectively. Cintrofin promoted the survival of cerebellar granule neurons (CGNs), in which cell death was induced either by potassium withdrawal or H2O2 treatment. Cintrofin induced neurite outgrowth from CGNs, and this effect was inhibited by specific antibodies against both gp130 and LIFR, indicating that these receptors are involved in the effects of cintrofin. The C-terminal part of the peptide, corresponding to the D helix region of CNTF, was shown to be essential for the neuritogenic action of the peptide. CNTF and LIF induced neurite outgrowth in CGNs plated on laminin-coated slides. On uncoated slides, CNTF and LIF had no neuritogenic effect but were able to inhibit cintrofin-induced neuronal differentiation, indicating that cintrofin and cytokines compete for the same receptors. In addition, cintrofin induced the phosphorylation of STAT3, Akt, and ERK, indicating that it exerts cell signaling properties similar to those induced by CNTF and may be a valuable survival agent with possible therapeutic potential. Copyright © 2011 Elsevier GmbH. All rights reserved.

  3. Biosynthesis of silver nanoparticles

    African Journals Online (AJOL)

    SIMBU

    2013-05-22

    May 22, 2013 ... exposure to silver can cause agyrosis and argyria also; it is toxic to mammalian cells (Gong et al., 2007). The current investigation supports that use of silver ion or metallic silver as well as, silver nanoparticles can be exploited in medicine for burn treatment, dental materials, coating stainless steel materials, ...

  4. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.

    Directory of Open Access Journals (Sweden)

    Cendrine Tourette

    2014-06-01

    Full Text Available The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD. Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT in several models of Huntington's disease (HD. Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.

  5. Does the survival motor neuron copy number variation play a role in the onset and severity of sporadic amyotrophic lateral sclerosis in Malians?

    Directory of Open Access Journals (Sweden)

    Modibo Sangare

    2016-06-01

    Conclusion: Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.

  6. Bunina bodies in motor and non-motor neurons revisited: a pathological study of an ALS patient after long-term survival on a respirator.

    Science.gov (United States)

    Kimura, Tadashi; Jiang, Haishan; Konno, Takuya; Seto, Makiko; Iwanaga, Keisuke; Tsujihata, Mitsuhiro; Satoh, Akira; Onodera, Osamu; Kakita, Akiyoshi; Takahashi, Hitoshi

    2014-08-01

    Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs) found in the remaining lower motor neurons (LMNs) of patients with sporadic amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular pathology. We examined a case of SALS, unassociated with TDP-43 or C9ORF72 mutation, of 12 years duration in a 75-year-old man, who had received artificial respiratory support for 9 years, and showed widespread multisystem degeneration with TDP-43 pathology. Interestingly, in this patient, many NCIs reminiscent of BBs were observed in the oculomotor nucleus, medullary reticular formation and cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not been previously described, we performed ultrastructural and immunohistochemical studies of these NCIs to gain further insight into the nature of BBs. In each region, the ultrastructural features of these NCIs were shown to be identical to those of BBs previously described in LMNs. These three regions and the relatively well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were immunostained with antibodies against cystatin C (CC) and TDP-43. Importantly, it was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs, but not of non-motor neurons, and that in the cerebellar dentate nucleus, the ratio of neurons with BBs and TDP-43 inclusions/neurons with BBs was significantly lower than in other regions. These findings suggest that the occurrence of BBs with CC immunoreactivity is intrinsically associated with the particular cellular properties of LMNs, and that the mechanism responsible for the formation of BBs is distinct from that for TDP-43 inclusions. © 2014 Japanese Society of Neuropathology.

  7. MicroNeurotrophins Improve Survival in Motor Neuron-Astrocyte Co-Cultures but Do Not Improve Disease Phenotypes in a Mutant SOD1 Mouse Model of Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Kelly E Glajch

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a neurodegenerative disease caused by loss of motor neurons. ALS patients experience rapid deterioration in muscle function with an average lifespan of 3-5 years after diagnosis. Currently, the most effective therapeutic only extends lifespan by a few months, thus highlighting the need for new and improved therapies. Neurotrophic factors (NTFs are important for neuronal development, maintenance, and survival. NTF treatment has previously shown efficacy in pre-clinical ALS models. However, clinical trials using NTFs produced no major improvements in ALS patients, due in part to the limited blood brain barrier (BBB penetration. In this study we assessed the potential neuroprotective effects of a novel class of compounds known as MicroNeurotrophins (MNTs. MNTs are derivatives of Dehydroepiandrosterone (DHEA, an endogenous neurosteroid that can cross the BBB and bind to tyrosine kinase receptors mimicking the pro-survival effects of NTFs. Here we sought to determine whether MNTs were neuroprotective in two different models of ALS. Our results demonstrate that BNN27 (10 μM attenuated loss of motor neurons co-cultured with astrocytes derived from human ALS patients with SOD1 mutations via the reduction of oxidative stress. Additionally, in the G93A SOD1 mouse, BNN27 (10 mg/kg treatment attenuated motor behavioral impairment in the paw grip endurance and rotarod tasks at postnatal day 95 in female but not male mice. In contrast, BNN27 (10 mg/kg and 50 mg/kg treatment did not alter any other behavioral outcome or neuropathological marker in male or female mice. Lastly, BNN27 was not detected in post-mortem brain or spinal cord tissue of treated mice due to the rapid metabolism of BNN27 by mouse hepatocytes relative to human hepatocytes. Together, these findings demonstrate that BNN27 treatment failed to yield significant neuroprotective effects in the G93A SOD1 model likely due to its rapid rate of metabolism in

  8. Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases

    Science.gov (United States)

    Engstrom, Anna; Wang, Hao; Xia, Zhengui

    2015-01-01

    Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults. PMID:25967738

  9. Tempol moderately extends survival in a hSOD1(G93A ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A forms.

    Directory of Open Access Journals (Sweden)

    Edlaine Linares

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1(G93A . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS.

  10. Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway

    Directory of Open Access Journals (Sweden)

    Cheng-Chen Zhang

    2017-07-01

    Full Text Available Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6 and one new natural product (2 together with five known compounds (1,3–5,7 were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1 and a cyathane diterpenoid, erincine A (3, not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.

  11. Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway.

    Science.gov (United States)

    Zhang, Cheng-Chen; Cao, Chen-Yu; Kubo, Miwa; Harada, Kenichi; Yan, Xi-Tao; Fukuyama, Yoshiyasu; Gao, Jin-Ming

    2017-07-30

    Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound ( 6 ) and one new natural product ( 2 ) together with five known compounds ( 1 , 3 - 5 , 7 ) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester ( 1 ) and a cyathane diterpenoid, erincine A ( 3 ), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3 -promoted NGF-induced neurite outgrowth in PC12 cells.

  12. Optimization of silver-dielectric-silver nanoshell for sensing applications

    Energy Technology Data Exchange (ETDEWEB)

    Shirzaditabar, Farzad; Saliminasab, Maryam [Department of Physics, Razi University, Kermanshah 67144-15111 (Iran, Islamic Republic of)

    2013-08-15

    In this paper, resonance light scattering (RLS) properties of a silver-dielectric-silver nanoshell, based on quasi-static approach and plasmon hybridization theory, are investigated. Scattering spectrum of silver-dielectric-silver nanoshell has two intense and clearly separated RLS peaks and provides a potential for biosensing based on surface plasmon resonance and surface-enhanced Raman scattering. The two RLS peaks in silver-dielectric-silver nanoshell are optimized by tuning the geometrical dimensions. In addition, the optimal geometry is discussed to obtain the high sensitivity of silver-dielectric-silver nanoshell. As the silver core radius increases, the sensitivity of silver-dielectric-silver nanoshell decreases whereas increasing the middle dielectric thickness increases the sensitivity of silver-dielectric-silver nanoshell.

  13. Dielectric elastomeric bimorphs using electrolessly deposited silver electrodes

    Science.gov (United States)

    Goh, Simon Chun-Kiat; Lau, Gih-Keong

    2010-04-01

    Metallic thin films, which are widely used for micro-electronics circuits, are seldom used as the electrodes for dielectric elastomer actuators (DEA). This is because metalized film restrains the lateral strain of soft dielectric elastomer. In this paper, we demonstrated utilizing metalized elastomeric layers to make a bimorph capable of a large bending. A compliant silver electrode is deposited on onto a VHB tape (F-9469 PC) using electroless deposition method, as for mirror silvering. The deposited silver is 200 nm thick and highly conductively though having an uneven surface. A silvered DEA bimorph is made of an active layer of silvered VHB elastomers and a passive layer of polydimethylsiloxane (PDMS). Experiments show that the silvered dielectric elastomer actuator is capable of producing a large bending, with a curvature of 32 mm for a 20 mm length at a driving voltage of 3000V. In addition, the electrolessly silvered elastomeric capacitor (130 μm thick VHB as dielectric) exhibits a breakdown voltage of 4kV, higher than 2kV of the silver-greased capacitor. In addition, the silvered VHB layer is found to be able to self clear after electrical breakdown. It remains functional at a lower voltage after surviving an electrical breakdown.

  14. Endocannabinoid CB1 receptor activation upon global ischemia adversely impact recovery of reward and stress signaling molecules, neuronal survival and behavioral impulsivity.

    Science.gov (United States)

    Knowles, Megan Dunbar; de la Tremblaye, Patricia Barra; Azogu, Idu; Plamondon, Hélène

    2016-04-03

    Global cerebral ischemia in rodents, which mimics cardiac arrest in humans, is associated with a surge in endocannabinoids and increased transmission of dopamine and glutamate leading to excitotoxic cell death. The current study assessed the role of CB1 receptor activation at the moment of an ischemic insult on ensuing regulation of stress and reward signaling molecules, neuronal injury and anxiety-like behavior. Male Wistar rats were separated into 4 groups (n=10/group); sham and ischemic rats administered the CB1 endocannabinoid receptor antagonist AM251 (2mg/kg, i.p.) 30min prior to global cerebral ischemia, and vehicle-treated counterparts. The effects of CB1 receptor blockade on corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2), tyrosine hydroxylase (TH) and dopamine receptor 1 (DRD1) signaling expression, together with CA1 neuronal damage and anxiety-like behaviors were assessed. Our findings show attenuated CA1 injury and behavioral deficits in AM251-treated ischemic rats. AM251-pretreatment also partially or completely reversed ischemia-induced alterations in TH-ir expression at the hippocampus, ventral tegmental area (VTA), nucleus accumbens (NAc) and basolateral amygdala (BLA), normalized DRD1-ir at the medial forebrain bundle, and diminished BLA and PVN-CRH expression. All groups showed comparable vGluT2 expression at the BLA and PVN-parvocellular subdivision. These findings support a determinant role of CB1 receptor activation at time of ischemia on functional recovery. They also support "state-dependent" effects of endocannabinoids, raising considerations in the development of effective molecules to regulate HPA axis function and mood disorders following cardiac arrest and stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Whole-Body Exposure to (28)Si-Radiation Dose-Dependently Disrupts Dentate Gyrus Neurogenesis and Proliferation in the Short Term and New Neuron Survival and Contextual Fear Conditioning in the Long Term.

    Science.gov (United States)

    Whoolery, Cody W; Walker, Angela K; Richardson, Devon R; Lucero, Melanie J; Reynolds, Ryan P; Beddow, David H; Clark, K Lyles; Shih, Hung-Ying; LeBlanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Ahn, Francisca; Bulin, Sarah E; DeCarolis, Nathan A; Rivera, Phillip D; Chen, Benjamin P C; Yun, Sanghee; Eisch, Amelia J

    2017-11-01

    neurogenesis indices in male and female mice, although only male mice showed fewer surviving BrdU(+) cells in the long-term group. Fluorescent immunolabeling and confocal phenotypic analysis revealed that most surviving BrdU(+) cells in the long-term group expressed the neuronal marker NeuN, definitively confirming that exposure to 1 Gy (28)Si radiation decreased the number of surviving adult-generated neurons in male mice relative to both 0- and 0.2-Gy-irradiated mice. For hippocampal function assessment, 9-week-old male C57BL/6J mice received whole-body (28)Si-particle exposure and were then assessed long-term for performance on contextual and cued fear conditioning. In the context test the animals that received 0.2 Gy froze less relative to control animals, suggesting decreased hippocampal-dependent function. However, in the cued fear conditioning test, animals that received 1 Gy froze more during the pretone portion of the test, relative to controls and 0.2-Gy-irradiated mice, suggesting enhanced anxiety. Compared to previously reported studies, these data suggest that (28)Si-radiation exposure damages neurogenesis, but to a lesser extent than (56)Fe radiation and that low-dose (28)Si exposure induces abnormalities in hippocampal function, disrupting fear memory but also inducing anxiety-like behavior. Furthermore, exposure to (28)Si radiation decreased new neuron survival in long-term male groups but not females suggests that sex may be an important factor when performing brain health risk assessment for astronauts traveling in space.

  16. Intranasal PRGF-Endoret enhances neuronal survival and attenuates NF-κB-dependent inflammation process in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Orive, Gorka; Carro, Eva

    2015-04-10

    Parkinson's disease is a common neurodegenerative disorder of unknown pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Oxidative stress, microglial activation and inflammatory responses seem to contribute to the pathogenesis. Recent data showed that growth factors mediate neuroprotection in rodent models of Parkinson's disease, modulating pro-inflammatory processes. Based on our recent studies showing that plasma rich in growth factors (PRGF-Endoret) mediates neuroprotection as inflammatory moderator in Alzheimer's disease, in the present study we examined the effects of plasma rich in growth factors (PRGF-Endoret) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse as a translational therapeutic approach for Parkinson's disease. We found substantial neuroprotection by PRGF-Endoret in our model of Parkinson's disease, which resulted in diminished inflammatory responses and improved motor performance. Additionally, these effects were associated with robust reduction in nuclear transcription factor-κB (NF-κB) activation, and nitric oxide (NO), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) expression in the substantia nigra. We propose that PRGF-Endoret can prevent dopaminergic degeneration via an NF-κB-dependent signaling process. As the clinical safety profile of PRGF-Endoret is already established, these data suggest that PRGF-Endoret provides a novel neuroprotective strategy for Parkinson's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. The H3K27 Demethylase JMJD3 Is Required for Maintenance of the Embryonic Respiratory Neuronal Network, Neonatal Breathing, and Survival

    Directory of Open Access Journals (Sweden)

    Thomas Burgold

    2012-11-01

    Full Text Available JMJD3 (KDM6B antagonizes Polycomb silencing by demethylating lysine 27 on histone H3. The interplay of methyltransferases and demethylases at this residue is thought to underlie critical cell fate transitions, and the dynamics of H3K27me3 during neurogenesis posited for JMJD3 a critical role in the acquisition of neural fate. Despite evidence of its involvement in early neural commitment, however, its role in the emergence and maturation of the mammalian CNS remains unknown. Here, we inactivated Jmjd3 in the mouse and found that its loss causes perinatal lethality with the complete and selective disruption of the pre-Bötzinger complex (PBC, the pacemaker of the respiratory rhythm generator. Through genetic and electrophysiological approaches, we show that the enzymatic activity of JMJD3 is selectively required for the maintenance of the PBC and controls critical regulators of PBC activity, uncovering an unanticipated role of this enzyme in the late structuring and function of neuronal networks.

  18. Human axonal survival of motor neuron (a-SMN) protein stimulates axon growth, cell motility, C-C motif ligand 2 (CCL2), and insulin-like growth factor-1 (IGF1) production.

    Science.gov (United States)

    Locatelli, Denise; Terao, Mineko; Fratelli, Maddalena; Zanetti, Adriana; Kurosaki, Mami; Lupi, Monica; Barzago, Maria Monica; Uggetti, Andrea; Capra, Silvia; D'Errico, Paolo; Battaglia, Giorgio S; Garattini, Enrico

    2012-07-27

    Spinal muscular atrophy is a fatal genetic disease of motoneurons due to loss of full-length survival of motor neuron protein, the main product of the disease gene SMN1. Axonal SMN (a-SMN) is an alternatively spliced isoform of SMN1, generated by retention of intron 3. To study a-SMN function, we generated cellular clones for the expression of the protein in mouse motoneuron-like NSC34 cells. The model was instrumental in providing evidence that a-SMN decreases cell growth and plays an important role in the processes of axon growth and cellular motility. In our conditions, low levels of a-SMN expression were sufficient to trigger the observed biological effects, which were not modified by further increasing the amounts of the expressed protein. Differential transcriptome analysis led to the identification of novel a-SMN-regulated factors, i.e. the transcripts coding for the two chemokines, C-C motif ligands 2 and 7 (CCL2 and CCL7), as well as the neuronal and myotrophic factor, insulin-like growth factor-1 (IGF1). a-SMN-dependent induction of CCL2 and IGF1 mRNAs resulted in increased intracellular levels and secretion of the respective protein products. Induction of CCL2 contributes to the a-SMN effects, mediating part of the action on axon growth and random cell motility, as indicated by chemokine knockdown and re-addition studies. Our results shed new light on a-SMN function and the underlying molecular mechanisms. The data provide a rational framework to understand the role of a-SMN deficiency in the etiopathogenesis of spinal muscular atrophy.

  19. The silver ions contribution into the cytotoxic activity of silver and silver halides nanoparticles

    Science.gov (United States)

    Klimov, A. I.; Zherebin, P. M.; Gusev, A. A.; Kudrinskiy, A. A.; Krutyakov, Y. A.

    2015-11-01

    The biocidal action of silver nanoparticles capped with sodium citrate and silver halides nanoparticles capped with non-ionic surfactant polyoxyethylene(20)sorbitan monooleate (Tween 80®) against yeast cells Saccharomyces cerevisiae was compared to the effect produced by silver nitrate and studied through the measurement of cell loss and kinetics of K+ efflux from the cells. The cytotoxicity of the obtained colloids was strongly correlated with silver ion content in the dispersions. The results clearly indicated that silver and silver halides nanoparticles destroyed yeast cells through the intermediate producing of silver ions either by dissolving of salts or by oxidation of silver.

  20. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABAA, glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABAB, as well as an adenosine A1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  1. Copper and silver halates

    CERN Document Server

    Woolley, EM; Salomon, M

    2013-01-01

    Copper and Silver Halates is the third in a series of four volumes on inorganic metal halates. This volume presents critical evaluations and compilations for halate solubilities of the Group II metals. The solubility data included in this volume are those for the five compounds, copper chlorate and iodate, and silver chlorate, bromate and iodate.

  2. Silver delafossite oxides.

    Science.gov (United States)

    Sheets, William C; Stampler, Evan S; Bertoni, Mariana I; Sasaki, Makoto; Marks, Tobin J; Mason, Thomas O; Poeppelmeier, Kenneth R

    2008-04-07

    A single-step, low-temperature (<210 degrees C) and -pressure (<20 atm) hydrothermal method has been developed to synthesize a series of silver delafossites, AgBO2 (B = Al, Ga, Sc, and In). Experimental and computational studies were performed to understand the optical and electric properties of these silver delafossites, including the first in-depth study of AgAlO2 and AgScO2. Their properties were examined as a function of the trivalent cation radius and compared to those of copper delafossites to elucidate the role of both the A- and B-site cations. While optical band gaps for silver delafossites were larger and visible light absorption was lower than values previously reported for polycrystalline powder samples of copper delafossites, the conductivities of silver delafossites are similar or lower. Electronic structure calculations indicate that these properties are due to the scarcity of silver 4d states just below the valence band maximum.

  3. Mineral commodity profiles: Silver

    Science.gov (United States)

    Butterman, W.C.; Hilliard, Henry E.

    2005-01-01

    Overview -- Silver is one of the eight precious, or noble, metals; the others are gold and the six platinum-group metals (PGM). World mine production in 2001 was 18,700 metric tons (t) and came from mines in 60 countries; the 10 leading producing countries accounted for 86 percent of the total. The largest producer was Mexico, followed by Peru, Australia, and the United States. About 25 percent of the silver mined in the world in 2001 came from silver ores; 15 percent, from gold ores and the remaining 60 percent, from copper, lead, and zinc ores. In the United States, 14 percent of the silver mined in 2001 came from silver ores; 39 percent, from gold ores; 10 percent, from copper and copper-molybdenum ores; and 37 percent, from lead, zinc, and lead-zinc ores. The precious metal ores (gold and silver) came from 30 lode mines and 10 placer mines; the base-metal ores (copper, lead, molybdenum, and zinc) came from 24 lode mines. Placer mines yielded less than 1 percent of the national silver production. Silver was mined in 12 States, of which Nevada was by far the largest producer; it accounted for nearly one-third of the national total. The production of silver at domestic mines generated employment for about 1,100 mine and mill workers. The value of mined domestic silver was estimated to be $290 million. Of the nearly 27,000 t of world silver that was fabricated in 2001, about one-third went into jewelry and silverware, one-fourth into the light-sensitive compounds used in photography, and nearly all the remainder went for industrial uses, of which there were 7 substantial uses and many other small-volume uses. By comparison, 85 percent of the silver used in the United States went to photography and industrial uses, 8 percent to jewelry and silverware, and 7 percent to coins and medals. The United States was the largest consumer of silver followed by India, Japan, and Italy; the 13 largest consuming countries accounted for nearly 90 percent of the world total. In the

  4. Synthesis and characterization of dextran-capped silver nanoparticles with enhanced antibacterial activity.

    Science.gov (United States)

    Yang, Guili; Lin, Qiuxia; Wang, Chunren; Li, Junjie; Wang, Jian; Zhou, Jin; Wang, Yan; Wang, Changyong

    2012-05-01

    Dextran-capped silver nanoparticles were synthesized by reducing silver nitrate with NaBH4 in the presence of dextran as capping agent. The characters of silver nanoparticles were investigated using UV-Vis spectrophotometer, nano-grainsize analyzer, X-ray diffraction, and transmission electron microscopy. Results showed that the silver nanoparticles capped with dextran were in uniform shape and narrow size distribution. Moreover, compared with polyvinylpyrrolidone (PVP)-capped silver nanoparticles, the dextran-capped ones possessed better stability. Antibacterial tests of these silver nanoparticles were carried out for Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Results suggested that the dextran-capped silver nanoparticles had high antibacterial activity against both Gram-positive and Gram-negative bacteria. In addition, the cytotoxicity in vitro of the dextran-capped silver nanoparticles was investigated using mouse fibrosarcoma cells (L929). The toxicity was evaluated by the changes of cell morphology and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Results indicated that these silver nanoparticles had slight effect on the survival and proliferation of L-929 cells at their minimal inhibitory concentration (MIC). After modified by dextran, the physiochemical properties of the silver nanoparticles had been improved. We anticipated that these dextran-capped silver nanoparticles could be integrated into systems for biological and pharmaceutical applications.

  5. Postmitotic specification of Drosophila insulinergic neurons from pioneer neurons.

    Directory of Open Access Journals (Sweden)

    Irene Miguel-Aliaga

    2008-03-01

    Full Text Available Insulin and related peptides play important and conserved functions in growth and metabolism. Although Drosophila has proved useful for the genetic analysis of insulin functions, little is known about the transcription factors and cell lineages involved in insulin production. Within the embryonic central nervous system, the MP2 neuroblast divides once to generate a dMP2 neuron that initially functions as a pioneer, guiding the axons of other later-born embryonic neurons. Later during development, dMP2 neurons in anterior segments undergo apoptosis but their posterior counterparts persist. We show here that surviving posterior dMP2 neurons no longer function in axonal scaffolding but differentiate into neuroendocrine cells that express insulin-like peptide 7 (Ilp7 and innervate the hindgut. We find that the postmitotic transition from pioneer to insulin-producing neuron is a multistep process requiring retrograde bone morphogenetic protein (BMP signalling and four transcription factors: Abdominal-B, Hb9, Fork Head, and Dimmed. These five inputs contribute in a partially overlapping manner to combinatorial codes for dMP2 apoptosis, survival, and insulinergic differentiation. Ectopic reconstitution of this code is sufficient to activate Ilp7 expression in other postmitotic neurons. These studies reveal striking similarities between the transcription factors regulating insulin expression in insect neurons and mammalian pancreatic beta-cells.

  6. Noisy Neurons

    Indian Academy of Sciences (India)

    IAS Admin

    Nerves are fibres that conduct electrical signals and hence pass on information from and to the brain. Nerves are made of nerve cells called neurons (Figure 1). Instructions in our body are sent via electrical signals that present themselves as variations in the potential across neuronal membranes. These potential differences ...

  7. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...

  8. Neuronal responses to physiological stress

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger David John

    2012-01-01

    damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses...... include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review...... the responses of neurons to various physiological stressors at the molecular and cellular level....

  9. Ultrastable silver nanoparticles.

    Science.gov (United States)

    Desireddy, Anil; Conn, Brian E; Guo, Jingshu; Yoon, Bokwon; Barnett, Robert N; Monahan, Bradley M; Kirschbaum, Kristin; Griffith, Wendell P; Whetten, Robert L; Landman, Uzi; Bigioni, Terry P

    2013-09-19

    Noble-metal nanoparticles have had a substantial impact across a diverse range of fields, including catalysis, sensing, photochemistry, optoelectronics, energy conversion and medicine. Although silver has very desirable physical properties, good relative abundance and low cost, gold nanoparticles have been widely favoured owing to their proved stability and ease of use. Unlike gold, silver is notorious for its susceptibility to oxidation (tarnishing), which has limited the development of important silver-based nanomaterials. Despite two decades of synthetic efforts, silver nanoparticles that are inert or have long-term stability remain unrealized. Here we report a simple synthetic protocol for producing ultrastable silver nanoparticles, yielding a single-sized molecular product in very large quantities with quantitative yield and without the need for size sorting. The stability, purity and yield are substantially better than those for other metal nanoparticles, including gold, owing to an effective stabilization mechanism. The particular size and stoichiometry of the product were found to be insensitive to variations in synthesis parameters. The chemical stability and structural, electronic and optical properties can be understood using first-principles electronic structure theory based on an experimental single-crystal X-ray structure. Although several structures have been determined for protected gold nanoclusters, none has been reported so far for silver nanoparticles. The total structure of a thiolate-protected silver nanocluster reported here uncovers the unique structure of the silver thiolate protecting layer, consisting of Ag2S5 capping structures. The outstanding stability of the nanoparticle is attributed to a closed-shell 18-electron configuration with a large energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, an ultrastable 32-silver-atom excavated-dodecahedral core consisting of a hollow 12-silver

  10. Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process.

    Science.gov (United States)

    Zhao, Jia; Cheng, Yuan-Yuan; Fan, Wen; Yang, Chuan-Bin; Ye, Shui-Fen; Cui, Wei; Wei, Wei; Lao, Li-Xing; Cai, Jing; Han, Yi-Fan; Rong, Jian-Hui

    2015-01-01

    Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process. We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP-lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2, and HO-1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit. Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP-lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold. Mechanistic studies revealed: (1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase-1 (HO-1) pathways; (2) ERK1/2, PI3K/Akt, and HO-1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF-induced neuritogenesis in a timing-dependent manner. Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases. © 2014 John Wiley & Sons Ltd.

  11. A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes.

    Science.gov (United States)

    Iyalomhe, Osigbemhe; Chen, Yuanxiu; Allard, Joanne; Ntekim, Oyonumo; Johnson, Sheree; Bond, Vernon; Goerlitz, David; Li, James; Obisesan, Thomas O

    2015-09-01

    There is considerable support for the view that aerobic exercise may confer cognitive benefits to mild cognitively impaired elderly persons. However, the biological mechanisms mediating these effects are not entirely clear. As a preliminary step towards informing this gap in knowledge, we enrolled older adults confirmed to have mild cognitive impairment (MCI) in a 6-month exercise program. Male and female subjects were randomized into a 6-month program of either aerobic or stretch (control) exercise. Data collected from the first 10 completers, aerobic exercise (n=5) or stretch (control) exercise (n=5), were used to determine intervention-induced changes in the global gene expression profiles of the aerobic and stretch groups. Using microarray, we identified genes with altered expression (relative to baseline values) in response to the 6-month exercise intervention. Genes whose expression were altered by at least two-fold, and met the p-value cutoff of 0.01 were inputted into the Ingenuity Pathway Knowledge Base Library to generate gene-interaction networks. After a 6-month aerobic exercise-training, genes promoting inflammation became down-regulated, whereas genes having anti-inflammatory properties and those modulating immune function or promoting neuron survival and axon growth, became up-regulated (all fold change≥±2.0, paerobic program as opposed to the stretch group. We conclude that three distinct cellular pathways may collectively influence the training effects of aerobic exercise in MCI subjects. We plan to confirm these effects using rt-PCR and correlate such changes with the cognitive phenotype. Copyright © 2015. Published by Elsevier Inc.

  12. Heavy metals in locus ceruleus and motor neurons in motor neuron disease

    Science.gov (United States)

    2013-01-01

    Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

  13. Leaching of Silver from Silver-Impregnated Food Storage Containers

    Science.gov (United States)

    Hauri, James F.; Niece, Brian K.

    2011-01-01

    The use of silver in commercial products has proliferated in recent years owing to its antibacterial properties. Food containers impregnated with micro-sized silver promise long food life, but there is some concern because silver can leach out of the plastic and into the stored food. This laboratory experiment gives students the opportunity to…

  14. Genetics Home Reference: Silver syndrome

    Science.gov (United States)

    ... movement and sensations. Silver syndrome is a complex hereditary spastic paraplegia. The first sign of Silver syndrome is usually ... links) GeneReview: BSCL2-Related Neurologic Disorders/Seipinopathy GeneReview: Hereditary ... Paraplegia Foundation, Inc.: Treatments and Therapies ...

  15. Effect of salinity on growth of juvenile silver kob, Argyrosomus ...

    African Journals Online (AJOL)

    As part of the evaluation of new aquaculture species, the effect of environmental factors on growth, food conversion ratio and survival should be tested. In this study silver kob, Argyrosomus inodorus, were reared for 98 days at three salinities, of 15, 25, and 35, at an average water temperature of 18 °C. Fish were fed to ...

  16. Printing Silver Nanogrids on Glass

    Science.gov (United States)

    Sanders, Wesley C.; Valcarce, Ron; Iles, Peter; Smith, James S.; Glass, Gabe; Gomez, Jesus; Johnson, Glen; Johnston, Dan; Morham, Maclaine; Befus, Elliot; Oz, Aimee; Tomaraei, Mohammad

    2017-01-01

    This manuscript describes a laboratory experiment that provides students with an opportunity to create conductive silver nanogrids using polymeric templates. A microcontact-printed polyvinylpyrrolidone grid directs the citrate-induced reduction of silver ions for the fabrication of silver nanogrids on glass substrates. In addition to…

  17. Silver-palladium cathode

    Energy Technology Data Exchange (ETDEWEB)

    Poizot, Philippe [Laboratoire de Reactivite et Chimie des Solides, UMR CNRS 6007, Universite de Picardie Jules Verne, 33 rue Saint-Leu, 80039 Amiens Cedex (France); Simonet, Jacques, E-mail: jacques.simonet@univ-rennes1.f [Laboratoire MaCSE, UMR CNRS 6226, Universite de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex (France)

    2010-12-15

    The formation of silver-palladium electrodes is described. It mainly corresponds to the palladization of silver by means of treatment with palladium salts (nitrate and sulphate) in acidic media. Other ways may exist such as the modification of solid conductors like carbons by deposition of a silver-palladium alloy. By using those electrodes in polar aprotic solvents, the one-electron cleavage of carbon-halogen bonds of most alkyl iodides and bromides may yield free alkyl radicals. Coupling and cross-coupling reactions can easily be carried out at such electrodes. The present review aims at discussing the electro-catalytic process as well as providing an update on the state of the art on this new mode of scission regarding carbon-heteroatom bonds.

  18. Silver-Russell syndrome

    Directory of Open Access Journals (Sweden)

    Shohela Akhter

    2016-08-01

    Full Text Available Silver-Russell syndrome is clinically and genetically a heterogeneous disorder. In most of the cases, etiology is unknown, only in 10% cases defect in chromosome 7 is identified. It bas distinctive facial features and asymmetric limbs. Most predominant symptom is growth failure. A case of Silver-Russell syndrome reported here who presented with growth failure, hemihypertrophy ofleft side oftbe body, dysmorphic facial profile and difficulty in speech. Counseling was done with the parents regarding the etiology, progression and outcome of the disease.

  19. War silver coins

    Directory of Open Access Journals (Sweden)

    Pantelić Svetlana

    2016-01-01

    Full Text Available There were two issues of silver 50-para, 1- and 2-dinar coins minted in the Parisian minting house marked with the year 1915 and bearing the image of King Petar I Karadjordjevic. Minted during the I World War, these two issues of silver coins only differed in that the first one had the specified name of the engraver (Schwarte, whereas the second issue had the engraver's name left out. These coins were used as the official legal tender until 28 June 1931.

  20. Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrPSc) deposition in sporadic Creutzfeldt-Jakob disease supports a pathogenic role for small PrPSc deposits common to the various molecular subtypes.

    Science.gov (United States)

    Faucheux, B A; Morain, E; Diouron, V; Brandel, J-P; Salomon, D; Sazdovitch, V; Privat, N; Laplanche, J-L; Hauw, J-J; Haïk, S

    2011-08-01

    Neuronal death is a major neuropathological hallmark in prion diseases. The association between the accumulation of the disease-related prion protein (PrP(Sc) ) and neuronal loss varies within the wide spectrum of prion diseases and their experimental models. In this study, we investigated the relationships between neuronal loss and PrP(Sc) deposition in the cerebellum from cases of the six subtypes of sporadic Creutzfeldt-Jakob disease (sCJD; n=100) that can be determined according to the M129V polymorphism of the human prion protein gene (PRNP) and PrP(Sc) molecular types. The numerical density of neurones was estimated with a computer-assisted image analysis system and the accumulation of PrP(Sc) deposits was scored. The scores of PrP(Sc) immunoreactive deposits of the punctate type (synaptic type) were correlated with neurone counts - the higher the score the higher the neuronal loss - in all sCJD subtypes. Large 5- to 50-µm-wide deposits (focal type) were found in sCJD-MV2 and sCJD-VV2 subtypes, and occasionally in a few cases of the other studied groups. By contrast, the highest scores for 5- to 50-µm-wide deposits observed in sCJD-MV2 subtype were not associated with higher neuronal loss. In addition, these scores were inversely correlated with neuronal counts in the sCJD-VV2 subtype. These results support a putative pathogenic role for small PrP(Sc) deposits common to the various sCJD subtypes. Furthermore, the observation of a lower loss of neurones associated with PrP(Sc) type-2 large deposits is consistent with a possible 'protective' role of aggregated deposits in both sCJD-MV2 and sCJD-VV2 subtypes. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

  1. Graphene-protected copper and silver plasmonics

    DEFF Research Database (Denmark)

    Kravets, V. G.; Jalil, R.; Kim, Y. J.

    2014-01-01

    suitable for plasmonic applications. To this end, there has been a continuous search for alternative plasmonic materials that are also compatible with complementary metal oxide semiconductor technology. Here we show that copper and silver protected by graphene are viable candidates. Copper films covered...... with one to a few graphene layers show excellent plasmonic characteristics. They can be used to fabricate plasmonic devices and survive for at least a year, even in wet and corroding conditions. As a proof of concept, we use the graphene-protected copper to demonstrate dielectric loaded plasmonic...... waveguides and test sensitivity of surface plasmon resonances. Our results are likely to initiate wide use of graphene-protected plasmonics....

  2. Loss of European silver eel passing a hydropower station

    DEFF Research Database (Denmark)

    Pedersen, Michael Ingemann; Jepsen, Niels; Aarestrup, Kim

    2012-01-01

    The aim of this study was to assess escapement success of silver eels, Anguilla anguilla (L.), in a lowland river while passing a reservoir and a hydropower station. It was hypothesized that passage success would be lowest at the hydropower station and that survival and migration speed would...... be highest in the free-flowing river section upstream the reservoir. Forty-five female silver eels 56–86 cm in length were tagged with acoustic transmitters and released in November 2006. Their migration was monitored via automatic listening stations (ALS) in various sections of the river, covering a total...

  3. Antibacterial activity and toxicity of silver - nanosilver versus ionic silver

    Science.gov (United States)

    Kvitek, L.; Panacek, A.; Prucek, R.; Soukupova, J.; Vanickova, M.; Kolar, M.; Zboril, R.

    2011-07-01

    The in vitro study of antibacterial activity of silver nanoparticles (NPs), prepared via modified Tollens process, revealed high antibacterial activity even at very low concentrations around several units of mg/L. These concentrations are comparable with concentrations of ionic silver revealing same antibacterial effect. However, such low concentrations of silver NPs did not show acute cytotoxicity to mammalian cells - this occurs at concentrations higher than 60 mg/L of silver, while the cytotoxic level of ionic silver is much more lower (approx. 1 mg/L). Moreover, the silver NPs exhibit lower acute ecotoxicity against the eukaryotic organisms such as Paramecium caudatum, Monoraphidium sp. and D. melanogaster. The silver NPs are toxic to these organisms at the concentrations higher than 30 mg/L of silver. On contrary, ionic silver retains its cytoxicity and ecotoxicity even at the concentration equal to 1 mg/L. The performed experiments demonstrate significantly lower toxicity of silver NPs against the eukaryotic organisms than against the prokaryotic organisms.

  4. Antibacterial activity and toxicity of silver - nanosilver versus ionic silver

    Energy Technology Data Exchange (ETDEWEB)

    Kvitek, L; Panacek, A; Prucek, R; Soukupova, J; Vanickova, M; Zboril, R [Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17. Listopadu 12, 77146 Olomouc (Czech Republic); Kolar, M, E-mail: ales.panacek@upol.cz [Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 77520 Olomouc (Czech Republic)

    2011-07-06

    The in vitro study of antibacterial activity of silver nanoparticles (NPs), prepared via modified Tollens process, revealed high antibacterial activity even at very low concentrations around several units of mg/L. These concentrations are comparable with concentrations of ionic silver revealing same antibacterial effect. However, such low concentrations of silver NPs did not show acute cytotoxicity to mammalian cells - this occurs at concentrations higher than 60 mg/L of silver, while the cytotoxic level of ionic silver is much more lower (approx. 1 mg/L). Moreover, the silver NPs exhibit lower acute ecotoxicity against the eukaryotic organisms such as Paramecium caudatum, Monoraphidium sp. and D. melanogaster. The silver NPs are toxic to these organisms at the concentrations higher than 30 mg/L of silver. On contrary, ionic silver retains its cytoxicity and ecotoxicity even at the concentration equal to 1 mg/L. The performed experiments demonstrate significantly lower toxicity of silver NPs against the eukaryotic organisms than against the prokaryotic organisms.

  5. Noisy Neurons

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 1. Noisy Neurons: Hodgkin-Huxley Model and Stochastic Variants. Shurti Paranjape. General Article Volume 20 Issue 1 January 2015 pp 34-43. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Nucleic acid nanomaterials: Silver-wired DNA

    Science.gov (United States)

    Auffinger, Pascal; Ennifar, Eric

    2017-10-01

    DNA double helical structures are supramolecular assemblies that are typically held together by classical Watson-Crick pairing. Now, nucleotide chelation of silver ions supports an extended silver-DNA hybrid duplex featuring an uninterrupted silver array.

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

    Science.gov (United States)

    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 (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.

  8. Orthodontic silver brazing alloys.

    Science.gov (United States)

    Brockhurst, P J; Pham, H L

    1989-10-01

    Orthodontic silver brazing alloys suffer from the presence of cadmium, excessive flow temperatures, and crevice corrosion on stainless steel. Seven alloys were examined. Two alloys contained cadmium. The lowest flow temperature observed was 629 degrees C for a cadmium alloy and 651 degrees C for two cadmium free alloys. Three alloys had corrosion resistance superior to the other solders. Addition of low melting temperature elements gallium and indium reduced flow temperature in some cases but produced brittleness in the brazing alloy.

  9. Resolving the detailed structure of cortical and thalamic neurons in the adult rat brain with refined biotinylated dextran amine labeling.

    Directory of Open Access Journals (Sweden)

    Changying Ling

    Full Text Available Biotinylated dextran amine (BDA has been used frequently for both anterograde and retrograde pathway tracing in the central nervous system. Typically, BDA labels axons and cell somas in sufficient detail to identify their topographical location accurately. However, BDA labeling often has proved to be inadequate to resolve the fine structural details of axon arbors or the dendrites of neurons at a distance from the site of BDA injection. To overcome this limitation, we varied several experimental parameters associated with the BDA labeling of neurons in the adult rat brain in order to improve the sensitivity of the method. Specifically, we compared the effect on labeling sensitivity of: (a using 3,000 or 10,000 MW BDA; (b injecting different volumes of BDA; (c co-injecting BDA with NMDA; and (d employing various post-injection survival times. Following the extracellular injection of BDA into the visual cortex, labeled cells and axons were observed in both cortical and thalamic areas of all animals studied. However, the detailed morphology of axon arbors and distal dendrites was evident only under optimal conditions for BDA labeling that take into account the: molecular weight of the BDA used, concentration and volume of BDA injected, post-injection survival time, and toning of the resolved BDA with gold and silver. In these instances, anterogradely labeled axons and retrogradely labeled dendrites were resolved in fine detail, approximating that which can be achieved with intracellularly injected compounds such as biocytin or fluorescent dyes.

  10. Biosynthesis of silver nanoparticles.

    Science.gov (United States)

    Poulose, Subin; Panda, Tapobrata; Nair, Praseetha P; Théodore, Thomas

    2014-02-01

    Metal nanoparticles have unique optical, electronic, and catalytic properties. There exist well-defined physical and chemical processes for their preparation. Those processes often yield small quantities of nanoparticles having undesired morphology, and involve high temperatures for the reaction and the use of hazardous chemicals. Relatively, the older technique of bioremediation of metals uses either microorganisms or their components for the production of nanoparticles. The nanoparticles obtained from bacteria, fungi, algae, plants and their components, etc. appear environment-friendly, as toxic chemicals are not used in the processes. In addition to this, the formation of nanoparticles takes place at almost normal temperature and pressure. Control of the shape and size of the nanoparticles is possible by appropriate selection of the pH and temperature. Three important steps are the bioconversion of Ag+ ions, conversion of desired crystals to nanoparticles, and nanoparticle stability. Generally, nanoparticles are characterized by the UV-visible spectroscopy and use of the electron microscope. Silver nanoparticles are used as antimicrobial agents and they possess antifungal, anti-inflammatory, and anti-angiogenic properties. This review highlights the biosynthesis of silver nanoparticles by various organisms, possible mechanisms of their synthesis, their characterization, and applications of silver nanoparticles.

  11. Survival of egg-laying controlling neuroendocrine cells during reproductive senescence of a mollusc

    NARCIS (Netherlands)

    Janse, C.

    2004-01-01

    During brain aging neuronal degradation occurs. In some neurons this may result in degeneration and cell death, still other neurons may survive and maintain their basic properties. The present study deals with survival of the egg-laying controlling neuroendocrine caudodorsal cells (CDCs) during

  12. Silver against Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Kirketerp-Møller, K.; Kristiansen, S.

    2007-01-01

    bacteria in both the planktonic and biofilm modes of growth. The action of silver on mature in vitro biofilms of Pseudomonas aeruginosa, a primary pathogen of chronic infected wounds, was investigated. The results show that silver is very effective against mature biofilms of P. aeruginosa...

  13. Corrosion protection for silver reflectors

    Science.gov (United States)

    Arendt, Paul N.; Scott, Marion L.

    1991-12-31

    A method of protecting silver reflectors from damage caused by contact with gaseous substances which are often present in the atmosphere and a silver reflector which is so protected. The inventive method comprises at least partially coating a reflector with a metal oxide such as aluminum oxide to a thickness of 15 .ANG. or less.

  14. Cognition and behaviour in motor neurone disease.

    Science.gov (United States)

    Lillo, Patricia; Hodges, John R

    2010-12-01

    Motor neurone disease has traditionally been considered a pure motor syndrome which spares aspects of cognition and behaviour, although in recent years it has been suggested that up to 50% of patients with motor neurone disease may develop frontal dysfunction which, in some cases, is severe enough to reach criteria for frontotemporal dementia. We review the cognitive and behavioural changes in motor neurone disease emphasizing the recent advances. A major advance in pathology has been the recent discovery of TDP-43 and FUS inclusions as the key components in cases of motor neurone disease, frontotemporal dementia-motor neurone disease and some cases with pure frontotemporal dementia. In addition, mutations in TARDBP and FUS genes have been reported in recent years. Longitudinal studies showed that progression of cognitive impairment over the course of motor neurone disease appears to be mild and occurs only in a proportion of motor neurone disease patients. The presence of cognitive impairment seems to be related to a faster disease and a shorter survival. Motor neurone disease is a multi-system disorder which overlaps with frontotemporal dementia. Behavioural and cognitive changes appear to occur in a subset of patients with motor neurone disease, but the cause of this variability remains unclear.

  15. Neurotrophic requirements of human motor neurons defined using amplified and purified stem cell-derived cultures.

    Directory of Open Access Journals (Sweden)

    Nuno Jorge Lamas

    Full Text Available Human motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC(50 1-2 pM. The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening.

  16. Oral toxicity of silver ions, silver nanoparticles and colloidal silver – a review

    DEFF Research Database (Denmark)

    Hadrup, Niels; Lam, Henrik Rye

    2014-01-01

    Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin......, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts...... and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least...

  17. Forced neuronal interactions cause poor communication.

    Science.gov (United States)

    Krzisch, Marine; Toni, Nicolas

    2017-01-01

    Post-natal hippocampal neurogenesis plays a role in hippocampal function, and neurons born post-natally participate to spatial memory and mood control. However, a great proportion of granule neurons generated in the post-natal hippocampus are eliminated during the first 3 weeks of their maturation, a mechanism that depends on their synaptic integration. In a recent study, we examined the possibility of enhancing the synaptic integration of neurons born post-natally, by specifically overexpressing synaptic cell adhesion molecules in these cells. Synaptic cell adhesion molecules are transmembrane proteins mediating the physical connection between pre- and post-synaptic neurons at the synapse, and their overexpression enhances synapse formation. Accordingly, we found that overexpressing synaptic adhesion molecules increased the synaptic integration and survival of newborn neurons. Surprisingly, the synaptic adhesion molecule with the strongest effect on new neurons' survival, Neuroligin-2A, decreased memory performances in a water maze task. We present here hypotheses explaining these surprising results, in the light of the current knowledge of the mechanisms of synaptic integration of new neurons in the post-natal hippocampus.

  18. Analysis of the growth characteristics of a 450-year-old silver fir tree

    Directory of Open Access Journals (Sweden)

    Pantić Damjan

    2015-01-01

    Full Text Available The growth characteristics of silver fir are of high importance for selection forest management, and for the current aims laid out in Serbia’s forest management focused on increasing the share of silver firs in Serbia’s growing stock. With the objective of increasing the understanding of the growth characteristics of silver fir, the growth of two silver fir trees felled during forest site production research on Mt. Goč, located in Central Serbia, have been analyzed. Both trees showed significant differences in their growth dynamics over long periods as results of micro-site and micro-stand effects (primarily ambient light regime. The common growth characteristic of the two trees, a 450-year-old tree as the main study object (labeled Tree A and a 270-year-old Tree B is a long stagnation stage. For Tree A the latent phase, with small interruptions, lasted 410 years; one phase lasted 330 years in continuity, which is the longest period of silver fir stagnation recorded in Europe. Tree B showed a long-lasting stagnation stage that lasted 170 years. The long stagnation stage of Tree A, characterized by an average diameter increment of 1.4 mm/year (average growth ring width of 0.7 mm and an average height increment of 0.08 m/year, shows the extraordinary silver fir capacity for physiological survival in complete shade. This study adds to the existing knowledge of the shade tolerance of the silver fir. Therefore, the silver fir belongs to the group of extremely shade-tolerant tree species. This characteristic makes silver fir an irreplaceable tree species in the selection forest structure. It offers a wide range of silvicultural flexibility in the management of these forests, and is applicable to silver fir selection Serbia’s forests. [Projekat Ministarstva nauke Republike Srbije, br. EVBR 37008: Sustainable management of total forest potentials in the Republic of Serbia

  19. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

    Science.gov (United States)

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V.; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G.; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H.

    2015-01-01

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro. PMID:25870293

  20. Toxicokinetics and toxicodynamics of differently coated silver nanoparticles and silver nitrate in Enchytraeus crypticus upon aqueous exposure in an inert sand medium

    NARCIS (Netherlands)

    Topuz, E.M.E.L.; van Gestel, C.A.M.

    2015-01-01

    The aim of the present study was to evaluate the effect of silver nanoparticles (AgNPs) on Enchytraeus crypticus, applying a combined toxicokinetics and toxicodynamics approach to understand the relationship between survival and the development of internal Ag concentrations in the animals over time.

  1. Silver nanoparticles in dentistry.

    Science.gov (United States)

    Noronha, Victor T; Paula, Amauri J; Durán, Gabriela; Galembeck, Andre; Cogo-Müller, Karina; Franz-Montan, Michelle; Durán, Nelson

    2017-10-01

    Silver nanoparticles (AgNPs) have been extensively studied for their antimicrobial properties, which provide an extensive applicability in dentistry. Because of this increasing interest in AgNPs, the objective of this paper was to review their use in nanocomposites; implant coatings; pre-formulation with antimicrobial activity against cariogenic pathogens, periodontal biofilm, fungal pathogens and endodontic bacteria; and other applications such as treatment of oral cancer and local anesthesia. Recent achievements in the study of the mechanism of action and the most important toxicological aspects are also presented. Systematic searches were carried out in Web of Science (ISI), Google, PubMed, SciFinder and EspaceNet databases with the keywords "silver nano* or AgNP*" and "dentist* or dental* or odontol*". A total of 155 peer-reviewed articles were reviewed. Most of them were published in the period of 2012-2017, demonstrating that this topic currently represents an important trend in dentistry research. In vitro studies reveal the excellent antimicrobial activity of AgNPs when associated with dental materials such as nanocomposites, acrylic resins, resin co-monomers, adhesives, intracanal medication, and implant coatings. Moreover, AgNPs were demonstrated to be interesting tools in the treatment of oral cancers due to their antitumor properties. The literature indicates that AgNPs are a promising system with important features such as antimicrobial, anti-inflammatory and antitumor activity, and a potential carrier in sustained drug delivery. However, there are some aspects of the mechanisms of action of AgNPs, and some important toxicological aspects arising from the use of this system that must be completely elucidated. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  2. Vagal Sensory Neuron Subtypes that Differentially Control Breathing

    OpenAIRE

    Chang, Rui B.; Strochlic, David E.; Williams, Erika K.; Umans, Benjamin D.; Liberles, Stephen D.

    2015-01-01

    Breathing is essential for survival and under precise neural control. The vagus nerve is a major conduit between lung and brain required for normal respiration. Here, we identify two populations of mouse vagus nerve afferents (P2ry1, Npy2r), each a few hundred neurons, that exert powerful and opposing effects on breathing. Genetically guided anatomical mapping revealed that these neurons densely innervate the lung and send long-range projections to different brainstem targets. Npy2r neurons a...

  3. Extracellular clusterin promotes neuronal network complexity in vitro

    DEFF Research Database (Denmark)

    Wicher, Grzegorz; Velsecchi, Isabel; Charnay, Yves

    2008-01-01

    of cellular debris. Intracellularly, clusterin may regulate signal transduction and is upregulated after cell stress. After neural injury, clusterin may be involved in nerve cell survival and postinjury neuroplasticity. In this study, we investigated the role of extracellular clusterin on neuronal network...... complexity in vitro. Quantitative analysis of clustrin-treated neuronal cultures showed significantly higher network complexity. These findings suggest that in addition to previously demonstrated neuroprotective roles, clusterin may also be involved in neuronal process formation, elongation, and plasticity....

  4. Biological Mechanism of Silver Nanoparticle Toxicity

    Science.gov (United States)

    Armstrong, Najealicka Nicole

    Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further

  5. Distinctive glial and neuronal interfacing on nanocrystalline diamond.

    Directory of Open Access Journals (Sweden)

    Amel Bendali

    Full Text Available 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.

  6. Neuronal encoding of the switch from specific to generalized fear.

    Science.gov (United States)

    Ghosh, Supriya; Chattarji, Sumantra

    2015-01-01

    Fear memories are crucial for survival. However, excessive generalization of such memories, characterized by a failure to discriminate dangerous from safe stimuli, is common in anxiety disorders. Neuronal encoding of the transition from cue-specific to generalized fear is poorly understood. We identified distinct neuronal populations in the lateral amygdala (LA) of rats that signaled generalized versus cue-specific associations and determined how their distributions switched during fear generalization. Notably, the same LA neurons that were cue specific before the behavioral shift to generalized fear lost their specificity afterwards, thereby tilting the balance of activity toward a greater proportion of generalizing neurons. Neuronal activity in the LA, but not the auditory cortex, was necessary for fear generalization. Furthermore, targeted activation of cAMP-PKA signaling in the LA increased neuronal excitability of LA neurons and led to generalized fear. These results provide a cellular basis in the amygdala for the alteration of emotional states from normal to pathological fear.

  7. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  8. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates...

  9. Biosynthesis of silver nanoparticles | Silambarasan | African Journal ...

    African Journals Online (AJOL)

    friendly and exciting approach. Several microorganisms have been known to produce silver nanoparticles (Ag NPs), when silver molecules are exposed either intracellularly or extracellularly. Intracellular synthesis may accomplish a better ...

  10. Silver recovery from spent photographic solutions

    Energy Technology Data Exchange (ETDEWEB)

    Kunda, W.; Etsell, T.H.

    1991-04-12

    A process is disclosed for recovering silver sulfide from a silver-containing spent photographic fixer solution. The process is particularly suited for treating the fixer solution in a manner which enables recycling of the solution, and does not have the inefficiencies and high costs of alternative processes such as electrolysis. The process comprises introducing hydrosulfide ion into the silver-containing spent fixer solution to precipitate silver sulfide. The resultant precipitate is isolated from the fixer solution in order to remove silver from the solution. The process is especially suited for treating spent solutions which contain thiosulfate, in particular sodium or ammonium thiosulfate. The preferred hydrosulfide is either a sodium or ammonium hydrosulfide for precipitating silver in the form of silver sulfide. The quantity of hydrosulfide used is in the range of greater than 0.5 mole per mole of silver in the fixer solution. Experiments are described to illustrate the process of the invention. 3 figs., 5 tabs.

  11. Thermally induced morphological transition of silver fractals

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Solov'yov, Andrey; Kébaili, Nouari

    2014-01-01

    We present both experimental and theoretical study of thermally induced morphological transition of silver nanofractals. Experimentally, those nanofractals formed from deposition and diffusion of preformed silver clusters on cleaved graphite surfaces exhibit dendritic morphologies that are highly...

  12. Silver and Chan revisited

    Science.gov (United States)

    Walsh, E.; Arnold, R.; Savage, M. K.

    2013-10-01

    Seismic shear waves emitted by earthquakes can be modeled as plane (transverse) waves. When entering an anisotropic medium, they can be split into two orthogonal components moving at different speeds. This splitting occurs along an axis, the fast polarization, that is determined by geologic conditions. We present here a comprehensive analysis of the Silver and Chan (1991) method, used to obtain shear wave splitting parameters, comprising theoretical derivations and statistical tests of the assumptions used to construct the standard errors. We find discrepancies in the derivations of equations in their article, with the most important being a mistake in how the standard errors are calculated. Our simulations suggest that the degrees of freedom are being overestimated by this method, and consequently, the standard errors are too small. Using a set of S waveforms from very similar shallow earthquakes on Reunion Island, we perform a statistical analysis on the noise of these replicates and find that the assumption of Gaussian noise does not hold. Further, the properties of background noise differ substantially from the noise obtained from the shear wave splitting analysis. However, we find that the estimated standard errors for the fast polarization are comparable to the spread in the fast polarization parameters between events. Delay time errors appear to be comparable to delay time estimates once cycle skipping is accounted for. Future work using synthetic seismograms with simulated noise should be conducted to confirm this is the case for earthquakes in general.

  13. Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy

    Science.gov (United States)

    Schwab, Andrew J.; Ebert, Allison D.

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system. PMID:25054590

  14. Micropatterning Facilitates the Long-Term Growth and Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks.

    Science.gov (United States)

    Burbulla, Lena F; Beaumont, Kristin G; Mrksich, Milan; Krainc, Dimitri

    2016-08-01

    The discovery of induced pluripotent stem cells (iPSCs) and their application to patient-specific disease models offers new opportunities for studying the pathophysiology of neurological disorders. However, current methods for culturing iPSC-derived neuronal cells result in clustering of neurons, which precludes the analysis of individual neurons and defined neuronal networks. To address this challenge, cultures of human neurons on micropatterned surfaces are developed that promote neuronal survival over extended periods of time. This approach facilitates studies of neuronal development, cellular trafficking, and related mechanisms that require assessment of individual neurons and specific network connections. Importantly, micropatterns support the long-term stability of cultured neurons, which enables time-dependent analysis of cellular processes in living neurons. The approach described in this paper allows mechanistic studies of human neurons, both in terms of normal neuronal development and function, as well as time-dependent pathological processes, and provides a platform for testing of new therapeutics in neuropsychiatric disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The Mode of Action of Silver and Silver Halides Nanoparticles against Saccharomyces cerevisiae Cells

    Directory of Open Access Journals (Sweden)

    A. A. Kudrinskiy

    2014-01-01

    Full Text Available Silver and silver halides nanoparticles (NPs (Ag, AgCl, AgBr, and AgI capped with two different stabilizers (sodium citrate and nonionic surfactant Tween 80 were obtained via sodium borohydride reduction of silver nitrate in an aqueous solution. The effect of the biocidal action of as-prepared synthesized materials against yeast cells Saccharomyces cerevisiae was compared to the effect produced by silver nitrate and studied through the measurement of cell loss and kinetics of K+ efflux from the cells depending on concentration of silver. The results clearly indicate that the silver ions either remained in the dispersion of silver NPs and silver halides NPs after their synthesis or were generated afterwards by dissolving silver and silver halides particles playing a major part in the cytotoxic activity of NPs against yeast cells. It was also supposed that this activity most likely does not relate to the damage of cell membrane.

  16. Physiological response to acute silver exposure in the freshwater crayfish (Cambarus diogenes diogenes) - a model invertebrate?

    DEFF Research Database (Denmark)

    Grosell, Martin Hautopp; Brauner, C.J.; Kelly, S.P.

    2002-01-01

    Crayfish, Silver toxicity, Osmoregulatory disturbance, Silver accumulation, Unidirectional Na+ flux......Crayfish, Silver toxicity, Osmoregulatory disturbance, Silver accumulation, Unidirectional Na+ flux...

  17. Topical silver for treating infected wounds

    NARCIS (Netherlands)

    Vermeulen, H.; van Hattem, J. M.; Storm-Versloot, M. N.; Ubbink, D. T.

    2007-01-01

    BACKGROUND: Topical silver treatments and silver dressings are increasingly used for the local treatment of contaminated or infected wounds, however, there is a lack of clarity regarding the evidence for their effectiveness. OBJECTIVES: To evaluate the effects on wound healing of topical silver and

  18. Geometrical parameters effects on local electric field enhancement of silver-dielectric-silver multilayer nanoshell

    Energy Technology Data Exchange (ETDEWEB)

    Shirzaditabar, Farzad; Saliminasab, Maryam [Department of Physics, Razi University, Kermanshah 67144-15111 (Iran, Islamic Republic of)

    2013-05-15

    The local electric field enhancement at different points of silver-dielectric-silver nanoshell is investigated using quasi-static theory. Because of the symmetric and anti-symmetric coupling between surface plasmon of inner silver core and outer silver shell, the local electric field spectrum of silver-dielectric-silver has two distinct peaks at resonance wavelengths. The silver core size and middle dielectric thickness affect the local electric field enhancement at different points of silver-dielectric-silver nanoshell. Increasing the silver core radius always leads to blue shift of shorter resonance wavelength and red shift of longer resonance wavelength. We observed two distinct local electric field peaks, which are corresponded to the symmetric and anti-symmetric coupling between inner and outer surface plasmons. In a system with thick silver shell, local electric field enhancement is greater than a system with thin silver shell. However, the local electric field variations as a function of silver core radius in both systems are different at different points of nanoshell. The effects of the dielectric thickness variations on local electric field are different from those from silver core size variations. As the dielectric thickness is about 3 nm, the highest local electric field enhancement occurs at the surface of the inner silver core, where the symmetric and anti-symmetric modes are mixed together.

  19. Dietary fats significantly influence the survival of penumbral neurons in a rat model of chronic ischemic by modifying lipid mediators, inflammatory biomarkers, NOS production, and redox-dependent apoptotic signals.

    Science.gov (United States)

    Lausada, Natalia; Arnal, Nathalie; Astiz, Mariana; Marín, María Cristina; Lofeudo, Juan Manuel; Stringa, Pablo; Tacconi de Alaniz, María J; Tacconi de Gómez Dumm, Nelva; Hurtado de Catalfo, Graciela; Cristalli de Piñero, Norma; Pallanza de Stringa, María Cristina; Illara de Bozzolo, Eva María; Bozzarello, Enrique Gustavo; Cristalli, Diana Olga; Marra, Carlos Alberto

    2015-01-01

    Brain stroke is the third most important cause of death in developed countries. We studied the effect of different dietary lipids on the outcome of a permanent ischemic stroke rat model. Wistar rats were fed diets containing 7% commercial oils (S, soybean; O, olive; C, coconut; G, grape seed) for 35 d. Stroke was induced by permanent middle cerebral artery occlusion. Coronal slices from ischemic brains and sham-operated animals were supravitally stained. Penumbra and core volumes were calculated by image digitalization after 24, 48, and 72 h poststroke. Homogenates and mitochondrial fractions were prepared from different zones and analyzed by redox status, inflammatory markers, ceramide, and arachidonate content, phospholipase A2, NOS, and proteases. Soybean (S) and G diets were mainly prooxidative and proinflammatory by increasing the liberation of arachidonate and its transformation into prostaglandins. O was protective in terms of redox homeostatic balance, minor increases in lipid and protein damage, conservation of reduced glutathione, protective activation of NOS in penumbra, and net ratio of anti-to proinflammatory cytokines. Apoptosis (caspase-3, milli- and microcalpains) was less activated by O than by any other diet. Dietary lipids modulate NOS and PLA2 activities, ceramide production, and glutathione import into the mitochondrial matrix, finally determining the activation of the two main protease systems involved in programmed cell death. Olive oil appears to be a biological source for the isolation of protective agents that block the expansion of brain core at the expense of penumbral neurons. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Juvenil neuronal ceroid lipofuscinosis

    DEFF Research Database (Denmark)

    Ostergaard, J R; Hertz, Jens Michael

    1998-01-01

    Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The diseases can be differentiated into several subgroups according to age of onset, the clinical picture...

  1. Pyrethroid toxicity in silver catfish, Rhamdia quelen

    Directory of Open Access Journals (Sweden)

    Francisco P. Montanha

    2012-12-01

    Full Text Available This study aimed to determine both the lethal and sublethal concentrations of Cypermethrin in young Silver Catfish (Brazilian "Jundiá", Rhamdia quelen on aquatic environment during 96 hours, as well as to determine the Cypermethrin and Deltamethrin sublethal concentrations during the initial embryonic development period of Rhamdia quelen, and to verify their respective rates of fertilization, hatching and survival. Pyrethroid nowadays is a widely used insecticide, which presents a high toxicity to fish. In order to determine lethal and sublethal concentrations, 120 silver catfish were used; each one had an average weight of 59.58±4.50g and an average size of 20.33±2.34cm. Concentrations used were 0, 1.0, 1.5, 2.0, 2.5, 3.0, 5.0, 10.0, 15.0 and 20.0mg of Cypermethrin per liter of water (mg/L. Fish were exposed to the product in 30-liter fish tanks. In each fish tank there were four fishes and the product was applied three times, i.e., a total of twelve fish were exposed to the product at each application, and a total of 120 fish during the entire experiment (n=120. In order to determine the Cypermethrin and Deltamethrin sublethal concentrations during the initial embryonic development, ovulation induction was performed on female fishes using hormones, and then and egg collection was performed. The eggs were then hydrated and fertilized in Cypermethrin and Deltamethrin in different concentrations: 0.001, 0.01, 0.1, 1.0 and 10.0mg/L of Cypermethrin and 0.001, 0.01, 0.1, 0.5 and 1.0mg/L of Deltamethrin, in addition to the control group (0mg/L. After fertilization, the eggs were kept in containers with the respective pesticides of Cypermethrin and Deltamethrin until hatching, when hatching rate was verified. Then the alevins, from the hatching, were kept on their respective concentrations of Cypermethrin and Deltamethrin so that the survival rate could be analyzed regarding the tested insecticides, during both 12-hour and 24-hour periods

  2. Antituberculous effect of silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kreytsberg, G N; Gracheva, I E [Limited Liability Company ' Scientific and Production Association (NPO)' Likom' , 150049, Yaroslavl, Magistralnaya str., 32 (Russian Federation); Kibrik, B S [Yaroslavl State Medical Academy Russia, 150000, Yaroslavl, Revolutsionnaya str., 5 (Russian Federation); Golikov, I V, E-mail: likomm@yaroslavl.ru [Yaroslavl State Technical University Russia, 150023, Yaroslavl, Moskovskiy avenue, 88 (Russian Federation)

    2011-04-01

    The in vitro experiment, involving 1164 strains of the tuberculosis mycobacteria, exhibited a potentiating effect of silver nanoparticles on known antituberculous preparations in respect of overcoming drug-resistance of the causative agent. The in vitro experiment, based on the model of resistant tuberculosis, was performed on 65 white mice. An evident antituberculous effect of the nanocomposite on the basis of silver nanoparticles and isoniazid was proved. Toxicological assessment of the of nanopreparations was carried out. The performed research scientifically establishes efficacy and safety of the nanocomposite application in combination therapy of patients suffering from drug-resistant tuberculosis.

  3. Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

    Science.gov (United States)

    2014-01-01

    The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

  4. Influence of stochastic gene expression on the cell survival rheostat after traumatic brain injury.

    Science.gov (United States)

    Rojo, Daniel R; Prough, Donald S; Falduto, Michael T; Boone, Deborah R; Micci, Maria-Adelaide; Kahrig, Kristen M; Crookshanks, Jeanna M; Jimenez, Arnaldo; Uchida, Tatsuo; Cowart, Jeremy C; Hawkins, Bridget E; Avila, Marcela; DeWitt, Douglas S; Hellmich, Helen L

    2011-01-01

    Experimental evidence suggests that random, spontaneous (stochastic) fluctuations in gene expression have important biological consequences, including determination of cell fate and phenotypic variation within isogenic populations. We propose that fluctuations in gene expression represent a valuable tool to explore therapeutic strategies for patients who have suffered traumatic brain injury (TBI), for which there is no effective drug therapy. We have studied the effects of TBI on the hippocampus because TBI survivors commonly suffer cognitive problems that are associated with hippocampal damage. In our previous studies we separated dying and surviving hippocampal neurons by laser capture microdissection and observed unexplainable variations in post-TBI gene expression, even though dying and surviving neurons were adjacent and morphologically identical. We hypothesized that, in hippocampal neurons that subsequently are subjected to TBI, randomly increased pre-TBI expression of genes that are associated with neuroprotection predisposes neurons to survival; conversely, randomly decreased expression of these genes predisposes neurons to death. Thus, to identify genes that are associated with endogenous neuroprotection, we performed a comparative, high-resolution transcriptome analysis of dying and surviving hippocampal neurons in rats subjected to TBI. We found that surviving hippocampal neurons express a distinct molecular signature--increased expression of networks of genes that are associated with regeneration, cellular reprogramming, development, and synaptic plasticity. In dying neurons we found decreased expression of genes in those networks. Based on these data, we propose a hypothetical model in which hippocampal neuronal survival is determined by a rheostat that adds injury-induced genomic signals to expression of pro-survival genes, which pre-TBI varies randomly and spontaneously from neuron to neuron. We suggest that pharmacotherapeutic strategies that co

  5. Silver-Palladium Surfaces Inhibit Biofilm Formation

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Schroll, Casper; Hilbert, Lisbeth Rischel

    2009-01-01

    Undesired biofilm formation is a major concern in many areas. In the present study, we investigated biofilm-inhibiting properties of a silver-palladium surface that kills bacteria by generating microelectric fields and electrochemical redox processes. For evaluation of the biofilm inhibition...... efficacy and study of the biofilm inhibition mechanism, the silver-sensitive Escherichia coli J53 and the silver-resistant E. coli J53[pMG101] strains were used as model organisms, and batch and flow chamber setups were used as model systems. In the case of the silver-sensitive strain, the silver......-palladium surfaces killed the bacteria and prevented biofilm formation under conditions of low or high bacterial load. In the case of the silver-resistant strain, the silver-palladium surfaces killed surface-associated bacteria and prevented biofilm formation under conditions of low bacterial load, whereas under...

  6. Innovations’ Survival

    Directory of Open Access Journals (Sweden)

    Jakub Tabas

    2016-01-01

    Full Text Available Innovations currently represent a tool of maintaining the going concern of a business entity and its competitiveness. However, effects of innovations are not infinite and if an innovation should constantly preserve a life of business entity, it has to be a continual chain of innovations, i.e. continual process. Effective live of a single innovation is limited while the limitation is derived especially from industry. The paper provides the results of research on innovations effects in the financial performance of small and medium-sized enterprises in the Czech Republic. Objective of this paper is to determine the length and intensity of the effects of technical innovations in company’s financial performance. The economic effect of innovations has been measured at application of company’s gross production power while the Deviation Analysis has been applied for three years’ time series. Subsequently the Survival Analysis has been applied. The analyses are elaborated for three statistical samples of SMEs constructed in accordance to the industry. The results obtained show significant differences in innovations’ survival within these three samples of enterprises then. The results are quite specific for the industries, and are confronted and discussed with the results of authors’ former research on the issue.

  7. Purification of dopamine neurons by flow cytometry.

    Science.gov (United States)

    Kerr, C W; Lee, L J; Romero, A A; Stull, N D; Iacovitti, L

    1994-12-05

    The heterogeneity and preponderence of other cell types present in cultures has greatly impeded our ability to study dopamine neurons. In this report, we describe methods for isolating nearly pure dopamine neurons for study in culture. To do so, the lipid-soluble dye, 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (diI) was injected into the embryonic rat striata where it was taken up by nerve terminals and transported overnight back to the innervating perikarya in the ventral midbrain. Midbrain cells were then dissected, dissociated and separated on the basis of their (rhodamine) fluorescence by flow cytometry. Nearly all cells recovered as fluorescent positive (> 98%) were also immunoreactive for the dopamine specific enzyme tyrosine hydroxylase (80%-96%). Little contamination by other cells types was observed after labeling for specific neuronal and glial markers. Purified dopamine neurons continued to thrive and elaborate neuronal processes for at least 3 days in culture. Using this new model, it may now be possible to directly study the cellular and molecular processes regulating the survival and functioning of developing, injured and transplanted dopamine neurons.

  8. Plasmonic characterization of photo-induced silver nanoparticles extracted from silver halide based TEM film

    Energy Technology Data Exchange (ETDEWEB)

    Sudheer,, E-mail: sudheer@rrcat.gov.in; Tiwari, P.; Rai, V. N.; Srivastava, A. K. [Indus Synchrotrons Utilization Division, Raja Ramanna Centre for Advanced Technology Indore, Madhya Pradesh 452013 (India); Varshney, G. K. [Laser Bio-medical Applications & Instrumentation Division, Raja Ramanna Centre for Advanced Technology Indore, Madhya Pradesh 452013 (India)

    2016-05-23

    The plasmonic responses of silver nanoparticles extracted from silver halide based electron microscope film are investigated. Photo-reduction process is carried out to convert the silver halide grains into the metallic silver. The centrifuge technique is used for separating the silver nanoparticles from the residual solution. Morphological study performed by field emission scanning electron microscope (FESEM) shows that all the nanoparticles have an average diameter of ~120 nm with a high degree of mono dispersion in size. The localized surface plasmon resonance (LSPR) absorption peak at ~537 nm confirms the presence of large size silver nanoparticles.

  9. Embryonic retinal cells and support to mature retinal neurons.

    Science.gov (United States)

    Stanke, Jennifer J; Fischer, Andy J

    2010-04-01

    Purpose. There is a paucity of neuron replacement studies for retinal ganglion cells. Given the complex phenotype of these neurons, replacement of ganglion cells may be impossible. However, transplanted embryonic cells could provide factors that promote the survival of these neurons. The authors sought to determine whether transplanted embryonic retinal cells from various stages of development influence the survival of mature ganglion cells Methods. Acutely dissociated retinal cells, obtained from chick embryos, were transplanted into the vitreous chamber of posthatch chicken eyes after the ganglion cells were selectively damaged. Eight days after transplantation, numbers of ganglion cells were determined Results. Embryonic retinal cells from embryonic day (E)7, E10, and E11 promoted the survival of ganglion cells, whereas cells from earlier or later stages of development or from other tissue sources did not. The environment provided by the posthatch eye did not support the proliferation of the embryo-derived cells, unlike the environment provided by culture conditions. Furthermore, cells that migrated into the retina failed to express neuronal or glial markers; those that remained in the vitreous formed aggregates of neuronal and glial cells Conclusions. The environment provided within the mature retina does not support the differentiation and proliferation of retinal progenitors. Furthermore, embryo-derived cells likely produce secreted factors that promote the survival of damaged ganglion cells. Therefore, embryonic retinal cells could be applied as a cell-based survival therapy to treat neurodegenerative diseases of the retina.

  10. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Qvortrup, Klaus

    2011-01-01

    Background: The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food...... and food contact materials. Results: AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study...... in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of Ag...

  11. A theobromine derived silver N-heterocyclic carbene: synthesis, characterization, and antimicrobial efficacy studies on cystic fibrosis relevant pathogens.

    Science.gov (United States)

    Panzner, Matthew J; Hindi, Khadijah M; Wright, Brian D; Taylor, Jane B; Han, Daniel S; Youngs, Wiley J; Cannon, Carolyn L

    2009-09-21

    The increasing incidence of multidrug-resistant (MDR) pulmonary infections in the cystic fibrosis (CF) population has prompted the investigation of innovative silver based therapeutics. The functionalization of the naturally occurring xanthine theobromine at the N(1) nitrogen atom with an ethanol substituent followed by the methylation of the N(9) nitrogen atom gives the N-heterocyclic carbene precursor 1-(2-hydroxyethyl)-3,7,9-trimethylxanthinium iodide. The reaction of this xanthinium salt with silver acetate produces the highly hydrophilic silver carbene complex SCC8. The in vitro antimicrobial efficacy of this newly synthesized complex was evaluated with excellent results on a variety of virulent and MDR pathogens isolated from CF patients. A comparative in vivo study between the known caffeine derived silver carbene SCC1 and SCC8 demonstrated the ability of both complexes to improve the survival rates of mice in a pneumonia model utilizing the clinically isolated infectious strain of Pseudomonas aeruginosa PA M57-15.

  12. Early survival factor deprivation in the olfactory epithelium enhances activity-dependent survival

    Directory of Open Access Journals (Sweden)

    Adrien eFrançois

    2013-12-01

    Full Text Available The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs. However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226. We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population towards detection of environmental odorants.

  13. Early survival factor deprivation in the olfactory epithelium enhances activity-driven survival

    Science.gov (United States)

    François, Adrien; Laziz, Iman; Rimbaud, Stéphanie; Grebert, Denise; Durieux, Didier; Pajot-Augy, Edith; Meunier, Nicolas

    2013-01-01

    The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants. PMID:24399931

  14. Preparation of silver nanoparticles at low temperature

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Mini, E-mail: mishramini5@gmail.com [Centre of Environmental Science, Department of Botany, University of Allahabad, Allahabad, U.P. (India); Chauhan, Pratima, E-mail: mangu167@yahoo.co.in [Department of Physics, University of Allahabad, Allahabad U.P. (India)

    2016-04-13

    Silver from ancient time is used as antimicrobial agent in the bulk form but now with the advancement in nanotechnology silver in the form of nanoparticles shown potential effect against microbes which make us easy to fight with many diseases plants and animals. In this work silver nanoparticles were synthesized by chemical routes using sodium borohydride as reducing agent at low temperature. The particles were characterized through UV-Visible spectroscopy as well as X-Ray Diffraction. The UV-visible spectra of silver nanoparticles exhibited absorption at 425 cm; the crystallite size of the particles is between 19nm to 39nm. EDAX graph shows two peaks of silver and oxygen. Water absorbed by silver nanoparticles was removed by the calcinations.

  15. Biosynthesis of Silver Nanoparticles and Its Applications

    OpenAIRE

    M. Jannathul Firdhouse; Lalitha, P

    2015-01-01

    Silver nanoparticles possess unique properties which find myriad applications such as antimicrobial, anticancer, larvicidal, catalytic, and wound healing activities. Biogenic syntheses of silver nanoparticles using plants and their pharmacological and other potential applications are gaining momentum owing to its assured rewards. This critical review is aimed at providing an insight into the phytomediated synthesis of silver nanoparticles, its significant applications in various fields, and c...

  16. Multifunctionality of silver closo-boranes

    DEFF Research Database (Denmark)

    Paskevicius, Mark; Hansen, Bjarne R. S.; Jorgensen, Mathias

    2017-01-01

    Silver compounds share a rich history in technical applications including photography, catalysis, photocatalysis, cloud seeding and as antimicrobial agents. Here we present a class of silver compounds (Ag2B10H10 and Ag2B12H12) that are semiconductors with a bandgap at 2.3 eV in the green visible...... of silver closo-boranes and open up avenues in a wide range of fields including photocatalysis, solid state ionics and nano-wire production....

  17. Risk assessment of silver nanoparticles

    Science.gov (United States)

    Shipelin, V. A.; Gmoshinski, I. V.; Khotimchenko, S. A.

    2015-11-01

    Nanoparticles of metallic silver (Ag) are among the most widely used products of nanotechnology. Nanosized colloidal silver (NCS) is presented in many kinds of production as solutions of particles with diameter less than 100 nm. NCS is used in a variety of fields, including food supplements, medicines, cosmetics, packaging materials, disinfectants, water filters, and many others. Problems of toxicity and related safety of NCS for humans and environmental systems are recently overestimated basing on data of numerous toxicological studies in vitro and in vivo. The article discusses the results of current studies in recent years and the data of author's own experiments on studying the safety of NCS, that allows to move on to risk assessment of this nanomaterial presented in consumer products and environmental samples.

  18. Topical silver for infected wounds.

    Science.gov (United States)

    Beam, Joel W

    2009-01-01

    Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev. 2007(1);CD005486. What is the clinical evidence base for silver dressings in the management of contaminated and infected acute and chronic wounds? Investigations were identified by Cochrane Wounds Group Specialized Register (2006), CENTRAL (2006), MEDLINE (2002-2006), EMBASE (2002-2006), CINAHL (2002-2006), and digital dissertations (2006) searches. Product manufacturers were contacted to identify additional eligible studies. The search terms included wound infection, surgical wound infection, ulcer, wound healing, and silver. Each study fulfilled the following criteria: (1) The study was a randomized controlled trial of human participants that compared dressings containing silver with any dressings without silver, dressings with other antiseptics, or dressings with different dosages of silver. (2) The participants were aged 18 years and older with contaminated and infected open wounds of any cause. (3) The study had to evaluate the effectiveness of the dressings using an objective measure of healing. No language or publication status restrictions were imposed, and participants could be recruited in any care setting. Studies were excluded if the wounds were ostomies (surgically formed passages). Study quality assessment was conducted independently by 3 authors using the Dutch Institute for Health Care Improvement and Dutch Cochrane Centre protocols. Characteristics of the study, participants, interventions, and outcome measures were extracted by one author and verified by a second using a standard form. The principal outcome measure was healing (time to complete healing, rate of change in wound area and volume, number and proportion of wounds healed within trial period). Secondary measures were adverse events (eg, pain, maceration, erythema), dressing leakage, and wound odor. Based on the unique comparisons in the studies, a meta

  19. Purification of Dorsal Root Ganglion Neurons from Rat by Immunopanning

    OpenAIRE

    Zuchero, J. Bradley

    2014-01-01

    Dorsal root ganglion neurons (DRGs) are sensory neurons that facilitate somatosensation and have been used to study neurite outgrowth, regeneration, and degeneration and PNS and CNS myelination. Studies of DRGs have relied on cell isolation strategies that generally involve extended culture in the presence of antimitotic agents or other cytotoxic treatments that target dividing cells. The surviving cells typically are dependent on serum for growth. Other methods, involving purification of DRG...

  20. Dendro-dendritic bundling and shared synapses between gonadotropin-releasing hormone neurons

    Science.gov (United States)

    Campbell, Rebecca E.; Gaidamaka, Galina; Han, Seong-Kyu; Herbison, Allan E.

    2009-01-01

    The pulsatile release of gonadotropin-releasing hormone (GnRH) is critical for mammalian fertility, but the mechanisms underlying the synchronization of GnRH neurons are unknown. In the present study, the full extent of the GnRH neuron dendritic tree was visualized by patching and filling individual GnRH neurons with biocytin in acute brain slices from adult GnRH-green fluorescent protein (GFP) transgenic mice. Confocal analysis of 42 filled GnRH neurons from male and female adult mice revealed that the dendrites of the great majority of GnRH neurons (86%) formed multiple close appositions with dendrites of other GnRH neurons. Two types of interactions were encountered; the predominant interaction was one of vertical dendritic bundling where dendrites were found to wrap around each other in the same axis. The other interaction was one in which a GnRH neuron dendrite intercepted other GnRH neuron dendrites in a perpendicular fashion. Electron microscopy using pre-embedded, silver-enhanced immunogold labeling for both GnRH and GFP peptides in GnRH-GFP transgenic mice, confirmed that GnRH neuron dendrites were often immediately juxtaposed. Membrane specializations, including punctae and zonula adherens, were found connecting adjacent dendritic elements of GnRH neurons. Remarkably, individual afferent axon terminals were found to synapse with multiple GnRH neuron dendrites at sites of bundling. Together, these data demonstrate that GnRH neurons are not isolated from one another but, rather, interconnected via their long dendritic extensions. The observation of shared synaptic input to bundled GnRH neuron dendrites suggests a mechanism of GnRH neuron synchronization. PMID:19541658

  1. Disruption of Axonal Transport in Motor Neuron Diseases

    Directory of Open Access Journals (Sweden)

    Gen Sobue

    2012-01-01

    Full Text Available Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS. Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases.

  2. Modulation of neuronal dynamic range using two different adaptation mechanisms

    Science.gov (United States)

    Wang, Lei; Wang, Ye; Fu, Wen-long; Cao, Li-hong

    2017-01-01

    The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents) in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms, i.e. subthreshold and suprathreshold (spike-triggered) adaptation, our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range. Specifically, subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range, while suprathreshold adaptation has little influence on the neuronal dynamic range. Moreover, when stochastic noise was introduced into the adaptation mechanisms, the dynamic range was apparently enhanced, regardless of what state the neuron was in, e.g. adaptive or non-adaptive. Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms. Additionally, noise was a non-ignorable factor, which could effectively modulate the neuronal dynamic range. PMID:28469660

  3. Motor neurone disease - caring for the patient in general practice.

    Science.gov (United States)

    Zoing, Margaret; Kiernan, Matthew

    2011-12-01

    Motor neurone disease is a neurodegenerative disease that leads to progressive disability - and eventually death - within 2-3 years. This article describes the role of the general practitioner in caring for patients with motor neurone disease. The diagnosis of motor neurone disease relies on the presence of upper and lower motor neurone features. There is currently no pathognomic test for motor neurone disease and it largely remains a diagnosis of exclusion following an accurate clinical history, combined with basic screening blood investigations and structural imaging of the brain and spinal cord. Neuro-physiological studies may be useful as an ancillary diagnostic tool. Riluzole, an anti-glutamate agent, is the only medication shown to have a survival benefit in motor neurone disease and results in a slowing of disease progression by an estimated 3-6 months. Noninvasive ventilation may relieve symptoms related to respiratory insufficiency and prolong survival by up to 12 months. A multidisciplinary approach to management has been shown to improve the quality of life for patients as well as survival. The GP is often the first point-of contact when medical issues arise regarding management of disease related symptoms including sialorrhoea, dyspnoea, constipation and pain, through to percutaneous gastrostomy feeding tubes and maintenance of noninvasive ventilation. It is important to establish the patient's wishes for future care while they are still able to communicate easily.

  4. Biogenic silver nanoparticles associated with silver chloride nanoparticles (Ag@AgCl) produced by laccase from Trametes versicolor.

    Science.gov (United States)

    Durán, Nelson; Cuevas, Raphael; Cordi, Livia; Rubilar, Olga; Diez, Maria Cristina

    2014-01-01

    In the present study, semi-purified laccase from Trametes versicolor was applied for the synthesis of silver nanoparticles, and the properties of the produced nanoparticles were characterized. All of the analyses of the spectra indicated silver nanoparticle formation. A complete characterization of the silver nanoparticles showed that a complex of silver nanoparticles and silver ions was produced, with the majority of the particles having a Ag(2+) chemical structure. A hypothetical mechanistic scheme was proposed, suggesting that the main pathway that was used was the interaction of silver ions with the T1 site of laccase, producing silver nanoparticles with the concomitant inactivation of laccase activity and posterior complexing with silver ions.

  5. Uptake and elimination kinetics of silver nanoparticles and silver nitrate by Raphidocelis subcapitata: The influence of silver behaviour in solution

    NARCIS (Netherlands)

    Ribeiro, Fabianne; Gallego-Urrea, Julián Alberto; Goodhead, Rhys M.; van Gestel, C.A.M.; Moeger, Julian; Soares, Amadeu M.V.M.; Loureiro, Susana

    2015-01-01

    Raphidocelis subcapitata is a freshwater algae species that constitutes the basis of many aquatic trophic chains. In this study, R. subcapitata was used as a model species to investigate the kinetics of uptake and elimination of silver nanoparticles (AgNP) in comparison to silver nitrate

  6. Synthesis and antimicrobial effects of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    S kheybari

    2010-09-01

    Full Text Available "n  "n "nBackground and the purpose of the study:The most prominent nanoparticles for medical uses are nanosilver particles which are famous for their high anti-microbial activity. Silver ion has been known as a metal ion that exhibit anti-mold, anti-microbial and anti-algal properties for a long time. In particular, it is widely used as silver nitrate aqueous solution which has disinfecting and sterilizing actions. The purpose of this study was to evaluate the antimicrobial activity as well as physical properties of the silver nanoparticles prepared by chemical reduction method. "nMethods:Silver nanoparticles (NPs were prepared by reduction of silver nitrate in the presence of a reducing agent and also poly [N-vinylpyrolidone] (PVP as a stabilizer. Two kinds of NPs were synthesized by ethylene glycol (EG and glucose as reducing agent. The nanostructure and particle size of silver NPs were confirmed by scanning electron microscopy (SEM and laser particle analyzer (LPA. The formations of the silver NPs were monitored using ultraviolet-visible spectroscopy. The anti-bacterial activity of silver NPs were assessed by determination of their minimum inhibitory concentrations (MIC against the Gram positive (Staphylococcus aureus and Staphylococcus epidermidis as well as Gram-negative (Escherichia coli and Pseudomonas aeruginosa bacteria. "nResults and Conclusion:The silver nanoparticles were spherical with particle size between 10 to 250 nm. Analysis of the theoretical (Mie light scattering theory and experimental results showed that the silver NPs in colloidal solution had a diameter of approximately 50 nm. "nBoth colloidal silver NPs showed high anti-bacterial activity against Gram positive and Gram negative bacteria. Glucose nanosilver colloids showed a shorter killing time against most of the tested bacteria which could be due to their nanostructures and uniform size distribution patterns.

  7. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  8. Adult human bone marrow stromal spheres express neuronal traits in vitro and in a rat model of Parkinson's disease

    OpenAIRE

    Suon, Sokreine; Yang, Ming; Iacovitti, Lorraine

    2006-01-01

    Adult human bone marrow stromal cells (hMSCs) grown in suspension culture gave rise to spheres of neural progenitor (NP) cells, capable of expressing both dopaminergic (DA) and GABAergic (GABA) traits. After transplantation into the Parkinsonian rat, human NPs and neurons were present at 2 weeks. Although no DA neurons appeared to survive transplantation, there were abundant GABA neurons present in the graft. By 4 weeks, however, all cells had died. Finding ways to prolong survival and promot...

  9. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    Directory of Open Access Journals (Sweden)

    Mortensen Alicja

    2011-06-01

    Full Text Available Abstract Background The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs and silver acetate (AgAc to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. Results AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP. The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM, nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver. Conclusions The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver

  10. Electrically Conductive Silver Paste Obtained by Use of Silver Neodecanoate as Precursor

    Science.gov (United States)

    Shen, Longguang; Liu, Jianguo; Zeng, Xiaoyan; Ren, Zhao

    2015-02-01

    An electrically conductive silver paste has been prepared from an organometallic compound, silver neodecanoate, as silver precursor. The precursor was highly soluble in organic solvents and decomposed into metallic silver at low sintering temperatures (pseudoplastic liquid with viscosity in the range 6.5-9 Pa s. The paste was compatible with the micro-pen direct-writing process, enabling production of silver lines on a substrate. The electrical resistivity of the silver lines was 9 × 10-6 Ω cm after sintering at 115°C for 60 min, 5.8 × 10-6 Ω cm when sintered at 150°C for 60 min, and 3 × 10-6 Ω cm when sintered above 300°C, values which are similar to those of bulk silver. Hence, the prepared paste can be successfully used on flexible substrates such as polymers.

  11. Development of nanostructured silver vanadates decorated with silver nanoparticles as a novel antibacterial agent

    Energy Technology Data Exchange (ETDEWEB)

    Holtz, R D; Souza Filho, A G; Alves, O L [Laboratorio de Quimica do Estado Solido (LQES), Instituto de Quimica, Universidade Estadual de Campinas, CP 6154, 13081-970, Campinas-SP (Brazil); Brocchi, M; Martins, D [Departamento de Genetica, Evolucao and Bioagentes, Instituto de Biologia, Universidade Estadual de Campinas, Campinas-SP (Brazil); Duran, N, E-mail: rholtz@iqm.unicamp.br, E-mail: agsf@fisica.ufc.br, E-mail: oalves@iqm.unicamp.br [Laboratorio de Quimica Biologica, Instituto de Quimica, Universidade Estadual de Campinas, Campinas-SP (Brazil)

    2010-05-07

    In this work we report the synthesis, characterization and application of silver vanadate nanowires decorated with silver nanoparticles as a novel antibacterial agent. These hybrid materials were synthesized by a precipitation reaction of ammonium vanadate and silver nitrate followed by hydrothermal treatment. The silver vanadate nanowires have lengths of the order of microns and diameters around 60 nm. The silver nanoparticles decorating the nanowires present a diameter distribution varying from 1 to 20 nm. The influence of the pH of the reaction medium on the chemical structure and morphology of silver vanadates was studied and we found that synthesis performed at pH 5.5-6.0 led to silver vanadate nanowires with a higher morphological yield. The antimicrobial activity of these materials was evaluated against three strains of Staphylococcus aureus and very promising results were found. The minimum growth inhibiting concentration value against a MRSA strain was found to be ten folds lower than for the antibiotic oxacillin.

  12. Biosynthesis of silver nanoparticles synthesized by Aspergillus ...

    Indian Academy of Sciences (India)

    In the present study, biosynthesis of silver nanoparticles and its antioxidant, antimicrobial and cytotoxic activities were investigated. Silver nanoparticles were extracellularly synthesized using Aspergillus flavus and the formation of nanoparticles was observed after 72 h of incubation. The results recorded from colour ...

  13. Synthesis and characterization of fluorophore attached silver ...

    Indian Academy of Sciences (India)

    Administrator

    - sized using starch as both reducing and stabilizing agent. Such starch stabilized silver nanoparticles were attached with rhodamine 6G for in vivo studies. So far no in vivo study was done for silver nanoparticles in animals except for some in ...

  14. Preparation of amine coated silver nanoparticles using ...

    Indian Academy of Sciences (India)

    Administrator

    Abstract. This article presents a simple method towards the preparation of functionalized silver nano- particles in a continuous medium. Silver nanoparticles were obtained through AgNO3 chemical reduction in ethanol and triethylenetetramine was used to stabilize and functionalize the metal. The product was characterized ...

  15. ECO-FRIENDLY SYNTHESIS OF SILVER NANOPARTICLES ...

    African Journals Online (AJOL)

    userpc

    as medical diagnosis/therapy, solar cell development, water treatment, surface coating and cosmetic production. Bacterial synthesis of silver nanoparticles is regarded as eco-friendly due to minimal waste generated while being energy efficient. This study was aimed at synthesizing silver nanoparticles using Lactobacillus ...

  16. Intravesical silver nitrate for refractory hemorrhagic cystitis.

    Science.gov (United States)

    Montgomery, Brian D; Boorjian, Stephen A; Ziegelmann, Matthew J; Joyce, Daniel D; Linder, Brian J

    2016-09-01

    Hemorrhagic cystitis is a challenging clinical entity with limited evidence available to guide treatment. The use of intravesical silver nitrate has been reported, though supporting literature is sparse. Here, we sought to assess outcomes of patients treated with intravesical silver nitrate for refractory hemorrhagic cystitis. We identified nine patients with refractory hemorrhagic cystitis treated at our institution with intravesical silver nitrate between 2000-2015. All patients had failed previous continuous bladder irrigation with normal saline and clot evacuation. Treatment success was defined as requiring no additional therapy beyond normal saline irrigation after silver nitrate instillation prior to hospital discharge. Median patient age was 80 years (IQR 73, 82). Radiation was the most common etiology for hemorrhagic cystitis 89% (8/9). Two patients underwent high dose (0.1%-0.4%) silver nitrate under anesthesia, while the remaining seven were treated with doses from 0.01% to 0.1% via continuous bladder irrigation for a median of 3 days (range 2-4). All nine patients (100%) had persistent hematuria despite intravesical silver nitrate therapy, requiring additional interventions and red blood cell transfusion during the hospitalization. There were no identified complications related to intravesical silver nitrate instillation. Although well tolerated, we found that intravesical silver nitrate was ineffective for bleeding control, suggesting a limited role for this agent in the management of patients with hemorrhagic cystitis.

  17. Fluorescent silver nanoparticles via exploding wire technique

    Indian Academy of Sciences (India)

    (SPR) of silver nanoparticles has been studied extensively [1] concluding particle size, shape and surrounding environment dependence. However, only a few re- searchers were able to observe the fluorescence behavior of silver nanoparticles and hence research is going on in order to understand the physics behind the ...

  18. Silver disinfection in water distribution systems

    Science.gov (United States)

    Silvestry Rodriguez, Nadia

    Silver was evaluated as disinfectant to maintain water quality in water distribution system. It was used to inhibit growth of two opportunistic bacteria in planktonik form and in biofilm formation in Robbins devices with stainless steel and PVC surfaces. The results of this work show that silver is a potential secondary disinfectant to be used in water distribution systems.

  19. Preparation, Characterization and Antibacterial Properties of Silver ...

    African Journals Online (AJOL)

    Purpose: To study the effect of chitosan molecular weight on the physicochemical and antibacterial properties of silver-chitosan nanoparticles. Methods: A series of silver-chitosan nanoparticles of different sizes were produced using various molecular weight (MW) grades of chitosan by an aqueous chemical reduction ...

  20. Synthesis and characterization of fluorophore attached silver ...

    Indian Academy of Sciences (India)

    Silver nanoparticles stabilized by soluble starch were synthesized and characterized. in vivo studies in rats showed no toxicity and revealed their distribution in various tissues and permeability across BBB. This starch stabilized silver nanoparticles have good biological characteristics to act as a potential promising vector for ...

  1. Preparation of silver powder through glycerol process

    Indian Academy of Sciences (India)

    High purity fine silver powder with uniform particle morphology was prepared through glycerol process. The process involves reduction of silver nitrate by glycerol under atmospheric conditions at a temperature below 175°C. Glycerol, in this process, acts as a solvent as well as a reducing agent. The powders prepared ...

  2. The role of metallothionein II in neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Køhler, Lene B; Berezin, Vladimir; Bock, Elisabeth

    2003-01-01

    Metallothionein I and II (MT-I+II) are antioxidant and tissue protective factors. We have previously shown that MT-I+II prevent oxidative stress and apoptotic cell death and are of therapeutic value in brain inflammation. However, MT-I+II are expressed in glia and it remains to be elucidated if M...

  3. Protein Kinase Pathways That Regulate Neuronal Survival and Death

    Science.gov (United States)

    2004-08-01

    intracellular T. gondii replication. International Congress on Toxoplasmosis . Freising, Germany, 2001. 13. Linseman, DA, T Laessig, MK Meintzer, M...University of Colo- role in the regulation of metabolic pathways as well as preven- rado Cancer Center core facility. tion of cell death by insulin and

  4. Silver manganese oxide electrodes for lithium batteries

    Energy Technology Data Exchange (ETDEWEB)

    Thackeray, Michael M.; Vaughey, John T.; Dees, Dennis W.

    2006-05-09

    This invention relates to electrodes for non-aqueous lithium cells and batteries with silver manganese oxide positive electrodes, denoted AgxMnOy, in which x and y are such that the manganese ions in the charged or partially charged electrodes cells have an average oxidation state greater than 3.5. The silver manganese oxide electrodes optionally contain silver powder and/or silver foil to assist in current collection at the electrodes and to improve the power capability of the cells or batteries. The invention relates also to a method for preparing AgxMnOy electrodes by decomposition of a permanganate salt, such as AgMnO4, or by the decomposition of KMnO4 or LiMnO4 in the presence of a silver salt.

  5. Silver manganese oxide electrodes for lithium batteries

    Science.gov (United States)

    Thackeray, Michael M.; Vaughey, John T.; Dees, Dennis W.

    2006-05-09

    This invention relates to electrodes for non-aqueous lithium cells and batteries with silver manganese oxide positive electrodes, denoted AgxMnOy, in which x and y are such that the manganese ions in the charged or partially charged electrodes cells have an average oxidation state greater than 3.5. The silver manganese oxide electrodes optionally contain silver powder and/or silver foil to assist in current collection at the electrodes and to improve the power capability of the cells or batteries. The invention relates also to a method for preparing AgxMnOy electrodes by decomposition of a permanganate salt, such as AgMnO4, or by the decomposition of KMnO4 or LiMnO4 in the presence of a silver salt.

  6. Silver dressings--do they work?

    Science.gov (United States)

    2010-04-01

    The metal silver is well known to have antimicrobial properties and this underlies its incorporation into the many types of silver releasing wound dressings available in the UK. These products are classed as 'advanced' dressings and were developed primarily for difficult to heal wounds, chronic ulcers and extensive burns.1 The use of silver dressings has increased rapidly in recent years in the UK, with the amount spent on such products in the NHS being around pound23million in 2005 and around pound25million in 2006/7.2(,)3 The latter figure represents a quarter of the total cost of wound dressings, with one seventh of the wound dressing items prescribed being silver dressings.3 Here we discuss the evidence on the place of silver dressings in burns, chronic ulcers and acute wounds.

  7. PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients

    DEFF Research Database (Denmark)

    Liu, Yawei; Carlsson, Robert; Ambjørn, Malene

    2013-01-01

    Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. In general, tumor growth requires disruption of the tissue microenvironment, yet how this affects glioma progression is unknown. We studied program death-ligand (PD-L)1 in neurons and gliomas in tumors from GBM patients...... and associated the findings with clinical outcome. Remarkably, we found that upregulation of PD-L1 by neurons in tumor-adjacent brain tissue (TABT) associated positively with GBM patient survival, whereas lack of neuronal PD-L1 expression was associated with high PD-L1 in tumors and unfavorable prognosis...... in GBM patients, better survival in wild-type mice was associated with high neuronal PD-L1 in TABT and downregulation of PD-L1 in tumors, which was defective in Ifnb-/- mice. Our data indicated that neuronal PD-L1 signaling in brain cells was important for GBM patient survival. Reciprocal PD-L1...

  8. Roads to riches: making good the silver ore at Lavrion in Greece

    Directory of Open Access Journals (Sweden)

    Thilo Rehren

    2000-11-01

    Full Text Available It is well known that the strategic power of ancient Athens rested on its formidable navy, but the value to the Athenians - and later to the Romans- Of the silver mines of Attica is less well understood. The Institute's newly appointed Professor of Archaeological Materials and Technologies describes his investigation of the impressive ancient mining installations that survive near Lavrion in southern Attica.

  9. Synergistic Combination of Chitosan Acetate with Nanoparticle Silver as a Topical Antimicrobial: Efficacy against Bacterial Burn Infections ▿

    Science.gov (United States)

    Huang, Liyi; Dai, Tianhong; Xuan, Yi; Tegos, George P.; Hamblin, Michael R.

    2011-01-01

    Chitosan and nanoparticle silver are both materials with demonstrated antimicrobial properties and have been proposed singly or in combination as constituents of antimicrobial burn dressings. Here, we show that they combine synergistically to inhibit the in vitro growth of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria (Pseudomonas aeruginosa, Proteus mirabilis, and Acinetobacter baumannii), as judged by bioluminescence monitoring and isobolographic analysis, and also produce synergistic killing after 30 min of incubation, as measured by a CFU assay. The hypothesized explanation involves chitosan-mediated permeabilization of bacterial cells, allowing better penetration of silver ions into the cell. A dressing composed of freeze-dried chitosan acetate incorporating nanoparticle silver was compared with a dressing of chitosan acetate alone in an in vivo burn model infected with bioluminescent P. aeruginosa. The survival rates of mice treated with silver-chitosan or regular chitosan or left untreated were 64.3% (P = 0.0082 versus regular chitosan and P = 0.0003 versus the control), 21.4%, and 0%, respectively. Most of the fatalities occurred between 2 and 5 days postinfection. Silver-chitosan dressings effectively controlled the development of systemic sepsis, as shown by blood culture. These data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections. PMID:21502618

  10. Corrosion processes of triangular silver nanoparticles compared to bulk silver

    Energy Technology Data Exchange (ETDEWEB)

    Keast, V. J., E-mail: vicki.keast@newcastle.edu.au; Myles, T. A. [University of Newcastle, School of Mathematical and Physical Sciences (Australia); Shahcheraghi, N.; Cortie, M. B. [University of Technology Sydney, Institute for Nanoscale Technology (Australia)

    2016-02-15

    Excessive corrosion of silver nanoparticles is a significant impediment to their use in a variety of potential applications in the biosensing, plasmonic and antimicrobial fields. Here we examine the environmental degradation of triangular silver nanoparticles (AgNP) in laboratory air. In the early stages of corrosion, transmission electron microscopy shows that dissolution of the single-crystal, triangular, AgNP (side lengths 50–120 nm) is observed with the accompanying formation of smaller, polycrystalline Ag particles nearby. The new particles are then observed to corrode to Ag{sub 2}S and after 21 days nearly full corrosion has occurred, but some with minor Ag inclusions remaining. In contrast, a bulk Ag sheet, studied in cross section, showed an adherent corrosion layer of only around 20–50 nm in thickness after over a decade of being exposed to ambient air. The results have implications for antibacterial properties and ecotoxicology of AgNP during corrosion as the dissolution and reformation of Ag particles during corrosion will likely be accompanied by the release of Ag{sup +} ions.

  11. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  12. Expression of diagnostic neuronal markers and outcome in glioblastoma.

    Science.gov (United States)

    Donev, K; Scheithauer, B W; Rodriguez, F J; Jenkins, S

    2010-08-01

    High-grade gliomas featuring giant cells, often demonstrate immunoreactivity for neuronal markers, a finding prognostically significant according to some studies. We investigated this event in glioblastomas (GBM). Immunoexpression for synaptophysin, neurofilament protein, neuronal nuclear antigen, chromogranin and glial fibrillary acidic protein was analysed in 82 GBM including 11 fibrillary, 8 gemistocytic, 40 giant cell and 23 small cell examples. Survival was compared between tumours exhibiting (GBMpos) or lacking (GBMneg) neuronal markers and also between tumours expressing only one vs. two or more neuronal markers. Forty-five of the 82 tumours (54.8%) including 5 fibrillary, 5 gemistocytic, 30 giant cell and 5 small cell GBMs expressed at least one neuronal marker, synaptophysin being the most frequent (96%). There was no statistically significant difference in survival between GBMpos and GBMneg tumours, all cytologic subtypes combined (P = 0.22). The same was true when cytologic categories were compared. When only GBMpos tumours were analysed, there was a marginally significant difference in outcome between tumours positive for one vs. multiple markers (P = 0.05). This difference was influenced primarily by giant cell GBMs among which the survival time was significantly shorter in the multiple vs. single marker category (median 123 vs. 295 days, P = 0.014). This difference was not observed in the other GBM cell types. Ultrastructurally, rare neurosecretory granules in glial filament-rich cells were identified in one of four tumours studied. Neuronal marker expression is a frequent feature of GBM. Its prognostic significance is limited to the giant cell GBMs expressing two or more neuronal markers, these being associated with shorter survival.

  13. Green synthesis of silver nanoparticles from leaf extracts of ...

    African Journals Online (AJOL)

    In this work, metallic silver nanoparticles were synthesized from leaf extracts of Parquetina nigrescens and Synedrella nodiflora. Silver ion was reduced to metallic silver on treatment of AgNO solution with aqueous extracts of the 3 two plants within 30minutes. The effects of time and the volume of extract to silver salt solution ...

  14. 21 CFR 872.3840 - Endodontic silver point.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endodontic silver point. 872.3840 Section 872.3840...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3840 Endodontic silver point. (a) Identification. An endodontic silver point is a device made of silver intended for use during endodontic therapy to...

  15. Suitsetamisega võitlemisel ei aita inimeste kiusamine / Silver Meikar

    Index Scriptorium Estoniae

    Meikar, Silver, 1978-

    2004-01-01

    Suitsetamise vastu võitlemisel ei tohiks kasutada rangelt seadusi vaid võimaldada soodsalt osta suitsetamisvastaseid vahendeid, leiab autor. Vt. ka: Silver Meikar: Olen valmis hoidma Eesti edu; Silver Meikar saatis lugejakirja Saksamaa päevalehtedele; Arvamusi Silver Meikarist; Silver Meikar loobus paberkandjale trükitud seaduseelnõudest

  16. Nanopackaging of Silver using Spice Extract and their ...

    African Journals Online (AJOL)

    The aim of the present study was to synthesize silver nanoparticles using spice extracts as reducing agents and further evaluate their anti-microbial activities. Silver has been shown to possess antimicrobial activity. The silver nanoparticles were prepared by solvent evaporation method. The silver nanoparticles were ...

  17. Mycosynthesis of Silver Nanoparticles from Candida albicans and its ...

    African Journals Online (AJOL)

    Purpose: To produce and characterize silver nanoparticles using Candida albicans and evaluate its antibacterial properties. Methods: Extracellular silver nanoparticles were biosynthesized using C. albicans. The biomass obtained from cultures of C. albicans was used to synthesize silver nanoparticles in 1.5 mM silver ...

  18. Silver Uptake and Reuse of Biomass by Saccharomyces cerevisiae ...

    African Journals Online (AJOL)

    Studies were carried out on the recovery of bound silver and reuse of Chlorella emersonii and Saccharomyces cerevisiae biomass for further silver uptake after they were placed in contact with 20mg/l silver for 30 minutes to allow for maximum binding. It was found that 0.16M nitric acid gave the best recovery rates of silver.

  19. Electrospun polyacrylonitrile nanofibers loaded with silver nanoparticles by silver mirror reaction

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yongzheng; Li, Yajing; Zhang, Jianfeng; Yu, Zhongzhen; Yang, Dongzhi, E-mail: yangdz@mail.buct.edu.cn

    2015-06-01

    The silver mirror reaction (SMR) method was selected in this paper to modify electrospun polyacrylonitrile (PAN) nanofibers, and these nanofibers loaded with silver nanoparticles showed excellent antibacterial properties. PAN nanofibers were first pretreated in AgNO{sub 3} aqueous solution before the SMR process so that the silver nanoparticles were distributed evenly on the outer surface of the nanofibers. The final PAN nanofibers were characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), transmission electron microscopy (TEM), TEM-selected area electron diffraction (SAED), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). SEM, TEM micrographs and SAED patterns confirmed homogeneous dispersion of the silver nanoparticles which were composed of monocrystals with diameters 20–30 nm. EDS and XRD results showed that these monocrystals tended to form face-centered cubic single silver. TGA test indicated that the nanoparticles loaded on the nanofibers reached above 50 wt.%. This material was also evaluated by the viable cell-counting method. The results indicated that PAN nanofibers loaded with silver nanoparticles exhibited excellent antimicrobial activities against gram-negative Escherichia coli (E. coli), gram-positive Staphylococcus aureus (S. aureus) and the fungus Monilia albicans. Thus, this material had many potential applications in biomedical fields. - Highlights: • Silver mirror reaction was used to prepare nanofibers loaded with silver nanoparticles. • The SAED patterns demonstrated the monocrystallinity of silver nanocrystals. • The XRD results showed nanoparticles tended to be face-centered cubic single silver. • The material showed excellent antimicrobial activities against bacteria and fungi.

  20. Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain neurons

    DEFF Research Database (Denmark)

    Sautter, J; Meyer, Morten; Spenger, C

    1998-01-01

    Neural transplantation is an experimental therapy for Parkinson's disease. Pretreatment of fetal donor tissue with neurotrophic factors may improve survival of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat ventral mesencephalon were treated with brain...

  1. Vagal Sensory Neuron Subtypes that Differentially Control Breathing.

    Science.gov (United States)

    Chang, Rui B; Strochlic, David E; Williams, Erika K; Umans, Benjamin D; Liberles, Stephen D

    2015-04-23

    Breathing is essential for survival and under precise neural control. The vagus nerve is a major conduit between lung and brain required for normal respiration. Here, we identify two populations of mouse vagus nerve afferents (P2ry1, Npy2r), each a few hundred neurons, that exert powerful and opposing effects on breathing. Genetically guided anatomical mapping revealed that these neurons densely innervate the lung and send long-range projections to different brainstem targets. Npy2r neurons are largely slow-conducting C fibers, while P2ry1 neurons are largely fast-conducting A fibers that contact pulmonary endocrine cells (neuroepithelial bodies). Optogenetic stimulation of P2ry1 neurons acutely silences respiration, trapping animals in exhalation, while stimulating Npy2r neurons causes rapid, shallow breathing. Activating P2ry1 neurons did not impact heart rate or gastric pressure, other autonomic functions under vagal control. Thus, the vagus nerve contains intermingled sensory neurons constituting genetically definable labeled lines with different anatomical connections and physiological roles. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  3. Neuromorphic Silicon Neuron Circuits

    National Research Council Canada - National Science Library

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; Schaik, André van; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems...

  4. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  5. Lumping Izhikevich neurons

    OpenAIRE

    Visser Sid; van Gils Stephan A

    2014-01-01

    We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behaviour intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting Izhikevich neurons. In both cases, the lumped model is compared with the spiking network. There is excellent agreement in terms of duration and number of action potentials within the bursts, but there is ...

  6. Polystyrene Based Silver Selective Electrodes

    Directory of Open Access Journals (Sweden)

    Shiva Agarwal

    2002-06-01

    Full Text Available Silver(I selective sensors have been fabricated from polystyrene matrix membranes containing macrocycle, Me6(14 diene.2HClO4 as ionophore. Best performance was exhibited by the membrane having a composition macrocycle : Polystyrene in the ratio 15:1. This membrane worked well over a wide concentration range 5.0×10-6–1.0×10-1M of Ag+ with a near-Nernstian slope of 53.0 ± 1.0 mV per decade of Ag+ activity. The response time of the sensor is <15 s and the membrane can be used over a period of four months with good reproducibility. The proposed electrode works well in a wide pH range 2.5-9.0 and demonstrates good discriminating power over a number of mono-, di-, and trivalent cations. The sensor has also been used as an indicator electrode in the potentiometric titration of silver(II ions against NaCl solution. The sensor can also be used in non-aqueous medium with no significant change in the value of slope or working concentration range for the estimation of Ag+ in solution having up to 25% (v/v nonaqueous fraction.

  7. Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF.

    Science.gov (United States)

    Matsumoto, Tomoya; Rauskolb, Stefanie; Polack, Martin; Klose, Johannes; Kolbeck, Roland; Korte, Martin; Barde, Yves-Alain

    2008-02-01

    Pro- and mature BDNF activate very different receptors and intracellular pathways, potentially leading to either neuronal death or survival. Here we examined the biochemistry of endogenous BDNF in mouse neurons using sensitive reagents and found that pro-BDNF is rapidly converted intracellularly to mature BDNF, the latter being stored and released by excitatory input.

  8. Neuronal AKAP150 coordinates PKA and Epac-mediated PKB/Akt phosphorylation

    NARCIS (Netherlands)

    Nijholt, Ingrid M.; Dolga, Amalia M.; Ostroveanu, Anghelus; Luiten, Paul G. M.; Schmidt, Martina; Eisel, Ulrich L. M.

    2008-01-01

    In diverse neuronal processes ranging from neuronal survival to synaptic plasticity cyclic adenosine monophosphate (cAMP)-dependent signaling is tightly connected with the protein kinase B (PKB)/Akt pathway but the precise nature of this connection remains unknown. In the current study we

  9. Silver in health care: antimicrobial effects and safety in use.

    Science.gov (United States)

    Lansdown, Alan B G

    2006-01-01

    Silver has a long and intriguing history as an antibiotic in human health care. It has been developed for use in water purification, wound care, bone prostheses, reconstructive orthopaedic surgery, cardiac devices, catheters and surgical appliances. Advancing biotechnology has enabled incorporation of ionizable silver into fabrics for clinical use to reduce the risk of nosocomial infections and for personal hygiene. The antimicrobial action of silver or silver compounds is proportional to the bioactive silver ion (Ag(+)) released and its availability to interact with bacterial or fungal cell membranes. Silver metal and inorganic silver compounds ionize in the presence of water, body fluids or tissue exudates. The silver ion is biologically active and readily interacts with proteins, amino acid residues, free anions and receptors on mammalian and eukaryotic cell membranes. Bacterial (and probably fungal) sensitivity to silver is genetically determined and relates to the levels of intracellular silver uptake and its ability to interact and irreversibly denature key enzyme systems. Silver exhibits low toxicity in the human body, and minimal risk is expected due to clinical exposure by inhalation, ingestion, dermal application or through the urological or haematogenous route. Chronic ingestion or inhalation of silver preparations (especially colloidal silver) can lead to deposition of silver metal/silver sulphide particles in the skin (argyria), eye (argyrosis) and other organs. These are not life-threatening conditions but cosmetically undesirable. Silver is absorbed into the human body and enters the systemic circulation as a protein complex to be eliminated by the liver and kidneys. Silver metabolism is modulated by induction and binding to metallothioneins. This complex mitigates the cellular toxicity of silver and contributes to tissue repair. Silver allergy is a known contra-indication for using silver in medical devices or antibiotic textiles.

  10. Preparation and Characterization of Gelatin Nanofibers Containing Silver Nanoparticles

    OpenAIRE

    Lim Jeong; Won Ho Park

    2014-01-01

    Ag nanoparticles (NPs) were synthesized in formic acid aqueous solutions through chemical reduction. Formic acid was used for a reducing agent of Ag precursor and solvent of gelatin. Silver acetate, silver tetrafluoroborate, silver nitrate, and silver phosphate were used as Ag precursors. Ag+ ions were reduced into Ag NPs by formic acid. The formation of Ag NPs was characterized by a UV-Vis spectrophotometer. Ag NPs were quickly generated within a few minutes in silver nitrate (AgNO3)/formic ...

  11. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    Science.gov (United States)

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  12. Nanostructured Antibacterial Silver Deposited on Polypropylene Nonwovens

    Science.gov (United States)

    Hong-Bo, Wang; Jin-Yan, Wang; Qu-Fu, Wei; Jian-Han, Hong; Xiao-Yan, Zhao

    Nanostructured silver films were deposited on polypropylene (PP) nonwovens by RF magnetron sputter coating to obtain the antibacterial properties. Shake flask test was used to evaluate the antibacterial properties of the materials. Atomic force microscope (AFM) was utilized to observe the surface morphology. Energy-dispersive X-ray (EDX) was also employed to analyze the surface elemental compositions. The antibacterial results indicated that the prolonged deposition time led to a significant improvement in antibacterial effect, and sputtering power and argon pressure did not show obvious effect on antibacterial performance. It is believed that the total amount of silver ions released from the silver coating was increased as the deposition time increased. AFM images and quantitative analysis of EDX, respectively revealed that increase in deposition time led to the increased coverage of silver film and the increased silver weight percentage per unit surface, which provided evidences for the increased release rate of silver ions from the coating. Moreover, it was found that the optimum silver coating thickness was about 3 nm, taking antibacterial effect and cost of production into account.

  13. Deposition of amorphous carbon-silver composites

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Zarco, O. [Instituto de Investigaciones en Materiales, Universidad Nacional Autonoma de Mexico, Circuito Exterior s/n, Ciudad Universitaria. 04510, Mexico D. F. Mexico (Mexico); Rodil, S.E., E-mail: ser42@iim.unam.m [Instituto de Investigaciones en Materiales, Universidad Nacional Autonoma de Mexico, Circuito Exterior s/n, Ciudad Universitaria. 04510, Mexico D. F. Mexico (Mexico); Camacho-Lopez, M.A. [Facultad de Quimica, Universidad Autonoma del Estado de Mexico, Tollocan s/n, esq. Paseo Colon, Toluca, Estado de Mexico, 50110 (Mexico)

    2009-12-31

    Composites of amorphous carbon films and silver were deposited by co-sputtering, where the target (10 cm diameter) was of pure graphite with small inclusion of pure silver (less than 1 cm{sup 2}). The films were deposited under different powers, from 40 to 250 W, and different target-substrate distances. The substrate was earthed and rotated in order to obtain a uniform distribution of the silver content. The addition of the Ag piece into the target increased the deposition rate of the carbon films, which could be related to the higher sputter yield of the silver, but there seems to be also a contribution from a larger emission of secondary electrons from the Ag that enhances the plasma and therefore the sputtering process becomes more efficient. Scanning electron micrographs acquired using backscattered electrons showed that the silver was segregated from the carbon matrix, forming nanoparticles or larger clusters as the power was increased. The X-ray diffraction pattern showed that the silver was crystalline and the carbon matrix remained amorphous, although for certain conditions a peak attributed to fullerene-like structures was obtained. Finally, we used Raman spectroscopy to understand the bonding characteristics of the carbon-silver composites, finding that there are variations in the D/G ratio, which can be correlated to the observed structure and X-ray diffraction results.

  14. Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation.

    Science.gov (United States)

    Fröhlich, Dominik; Kuo, Wen Ping; Frühbeis, Carsten; Sun, Jyh-Jang; Zehendner, Christoph M; Luhmann, Heiko J; Pinto, Sheena; Toedling, Joern; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

    2014-09-26

    Exosomes are small membranous vesicles of endocytic origin that are released by almost every cell type. They exert versatile functions in intercellular communication important for many physiological and pathological processes. Recently, exosomes attracted interest with regard to their role in cell-cell communication in the nervous system. We have shown that exosomes released from oligodendrocytes upon stimulation with the neurotransmitter glutamate are internalized by neurons and enhance the neuronal stress tolerance. Here, we demonstrate that oligodendroglial exosomes also promote neuronal survival during oxygen-glucose deprivation, a model of cerebral ischaemia. We show the transfer from oligodendrocytes to neurons of superoxide dismutase and catalase, enzymes which are known to help cells to resist oxidative stress. Additionally, we identify various effects of oligodendroglial exosomes on neuronal physiology. Electrophysiological analysis using in vitro multi-electrode arrays revealed an increased firing rate of neurons exposed to oligodendroglial exosomes. Moreover, gene expression analysis and phosphorylation arrays uncovered differentially expressed genes and altered signal transduction pathways in neurons after exosome treatment. Our study thus provides new insight into the broad spectrum of action of oligodendroglial exosomes and their effects on neuronal physiology. The exchange of extracellular vesicles between neural cells may exhibit remarkable potential to impact brain performance. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  15. Silver Nanoparticles and Graphitic Carbon Through Thermal Decomposition of a Silver/Acetylenedicarboxylic Salt

    Directory of Open Access Journals (Sweden)

    Komninou Philomela

    2009-01-01

    Full Text Available Abstract Spherically shaped silver nanoparticles embedded in a carbon matrix were synthesized by thermal decomposition of a Ag(I/acetylenedicarboxylic acid salt. The silver nanoparticles, which are formed either by pyrolysis at 300 °C in an autoclave or thermolysis in xylene suspension at reflux temperature, are acting catalytically for the formation of graphite layers. Both reactions proceed through in situ reduction of the silver cations and polymerization of the central acetylene triple bonds and the exact temperature of the reaction can be monitored through DTA analysis. Interestingly, the thermal decomposition of this silver salt in xylene partly leads to a minor fraction of quasicrystalline silver, as established by HR-TEM analysis. The graphitic layers covering the silver nanoparticles are clearly seen in HR-TEM images and, furthermore, established by the presence of sp2carbon at the Raman spectrum of both samples.

  16. Efavirenz induces neuronal autophagy and mitochondrial alterations.

    Science.gov (United States)

    Purnell, Phillip R; Fox, Howard S

    2014-11-01

    Efavirenz (EFV) is a non-nucleoside reverse-transcriptase inhibitor in wide use for the treatment of human immunodeficiency virus infection. Although EFV is generally well tolerated, neuropsychiatric toxicity has been well documented. The toxic effects of EFV in hepatocytes and keratinocytes have been linked to mitochondrial perturbations and changes in autophagy. Here, we studied the effect of EFV on mitochondria and autophagy in neuronal cell lines and primary neurons. In SH-SY5Y cells, EFV induced a drop in ATP production, which coincided with increased autophagy, mitochondrial fragmentation, and mitochondrial depolarization. EFV-induced mitophagy was also detected by colocalization of mitochondria and autophagosomes and use of an outer mitochondrial membrane tandem fluorescent vector. Pharmacologic inhibition of autophagy with 3-methyladenine increased the cytotoxic effect of EFV, suggesting that autophagy promotes cell survival. EFV also reduces ATP production in primary neurons, induces autophagy, and changes mitochondrial morphology. Overall, EFV is able to acutely induce autophagy and mitochondrial changes in neurons. These changes may be involved in the mechanism leading to central nervous system toxicity observed in clinical EFV use. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Sharyn L Rossi

    2010-07-01

    Full Text Available Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit.In order to investigate the amenability of the injured adult spinal cord to motor neuron differentiation, we transplanted spinal cord injured animals with a high purity population of human motor neuron progenitors (hMNP derived from human embryonic stem cells (hESCs. In vitro, hMNPs displayed characteristic motor neuron-specific markers, a typical electrophysiological profile, functionally innervated human or rodent muscle, and secreted physiologically active growth factors that caused neurite branching and neuronal survival. hMNP transplantation into cervical SCI sites in adult rats resulted in suppression of intracellular signaling pathways associated with SCI pathogenesis, which correlated with greater endogenous neuronal survival and neurite branching. These neurotrophic effects were accompanied by significantly enhanced performance on all parameters of the balance beam task, as compared to controls. Interestingly, hMNP transplantation resulted in survival, differentiation, and site-specific integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near the SCI site reverted to a neuronal progenitor state, suggesting an environmental deficiency for neuronal maturation associated with SCI.These findings underscore the barriers imposed on neuronal differentiation of transplanted cells by the gliogenic nature of the injured spinal cord, and the physiological relevance of transplant-derived neurotrophic support to functional recovery.

  18. Presence of nanoparticles in wash water from conventional silver and nano-silver textiles.

    Science.gov (United States)

    Mitrano, Denise M; Rimmele, Elisa; Wichser, Adrian; Erni, Rolf; Height, Murray; Nowack, Bernd

    2014-07-22

    Questions about how to regulate nanoenhanced products regularly arise as researchers determine possible nanoparticle transformation(s). Focusing concern on the incorporation and subsequent release of nano-Ag in fabrics often overshadows the fact that many "conventional silver" antimicrobials such as ionic silver, AgCl, metallic Ag, and other forms will also form different species of silver. In this study we used a laboratory washing machine to simulate the household laundering of a number of textiles prepared with known conventional Ag or nano-Ag treatments and a commercially available fabric incorporating yarns coated with bulk metallic Ag. Serial filtration allowed for quantification of total Ag released in various size fractions (>0.45 μm, nano-Ag treatments. Incorporating nano-silver into the fiber (as opposed to surface treatments) yielded less total Ag during fabric washing. A variety of metallic Ag, AgCl, and Ag/S particles were observed in washing solution by TEM/EDX to various extents depending on the initial Ag speciation in the fabrics. Very similar particles were also observed when dissolved ionic Ag was added directly into the washing liquid. On the basis of the present study, we can state that all silver-treated textiles, regardless of whether the treatment is "conventional" or "nano", can be a source of silver nanoparticles in washing solution when laundering fabrics. Indeed, in this study we observed that textiles treated with "conventional" silver have equal or greater propensity to form nano-silver particles during washing conditions than those treated with "nano"-silver. This fact needs to be strongly considered when addressing the risks of nano-silver and emphasizes that regulatory assessment of nano-silver warrants a similar approach to conventional silver.

  19. Silver deposition on stainless steel container surfaces in contact with disinfectant silver aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Petala, M., E-mail: petala@civil.auth.gr [Department of Civil Engineering, Aristotle University of Thessaloniki, Thessaloniki, 54124 (Greece); Tsiridis, V. [Department of Civil Engineering, Aristotle University of Thessaloniki, Thessaloniki, 54124 (Greece); Mintsouli, I. [Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, 54124 (Greece); Pliatsikas, N. [Department of Physics, Aristotle University of Thessaloniki, Thessaloniki, 54124 (Greece); Spanos, Th. [Department of Petroleum and Mechanical Engineering Sciences, Eastern Macedonia and Thrace Institute of Technology, Kavala, 65404 (Greece); Rebeyre, P. [ESA/ESTEC, P.O.Box 299, 2200 AG, Noordwijk (Netherlands); Darakas, E. [Department of Civil Engineering, Aristotle University of Thessaloniki, Thessaloniki, 54124 (Greece); Patsalas, P.; Vourlias, G. [Department of Physics, Aristotle University of Thessaloniki, Thessaloniki, 54124 (Greece); Kostoglou, M.; Sotiropoulos, S.; Karapantsios, Th. [Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, 54124 (Greece)

    2017-02-28

    Highlights: • Silver is one of the biocides of water consumed in the International Space Station. • Ionic silver is depleted from potable water when in contact with stainless steel (SS). • SEM and XPS analysis reveal a uniform silver deposition over the SS surface. • Silver deposits in its metallic form, in line with a galvanic deposition mechanism. • Evidence is provided that Cr and/ or Ni oxide builds-up on SS surfaces. - Abstract: Silver is the preservative used on the Russian segment of the International Space Station (ISS) to prevent microbial proliferation within potable water supplies. Yet, in the frame of the European Automated Transfer Vehicle (ATV) missions to ISS, silver depletion from water has been detected during ground transportation of this water to launch site, thereby indicating a degradation of water quality. This study investigates the silver loss from water when in contact with stainless steel surfaces. Experiments are conducted with several types of stainless steel surfaces being exposed to water containing 10 or 0.5 mg/L silver ions. Results show that silver deposits on stainless steel surfaces even when a passivation layer protects the metallic surface. The highest protection to silver deposition is offered by acid passivated and electropolished SS 316L. SEM and XPS experiments were carried out at several locations of the sample area that was in contact with the Ag solution and found similar morphological (SEM) and compositional (sputter-etch XPS) results. The results reveal that silver deposits uniformly across the wetted surface to a thickness larger than 3 nm. Moreover, evidence is provided that silver deposits in its metallic form on all stainless steel surfaces, in line with a galvanic deposition mechanism. Combination of ICP-MS and XPS results suggests a mechanism for Ag deposition/reduction with simultaneous substrate oxidation resulting in oxide growth at the exposed stainless steel surface.

  20. Thermal decomposition as route for silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Navaladian S

    2006-01-01

    Full Text Available AbstractSingle crystalline silver nanoparticles have been synthesized by thermal decomposition of silver oxalate in water and in ethylene glycol. Polyvinyl alcohol (PVA was employed as a capping agent. The particles were spherical in shape with size below 10 nm. The chemical reduction of silver oxalate by PVA was also observed. Increase of the polymer concentration led to a decrease in the size of Ag particles. Ag nanoparticle was not formed in the absence of PVA. Antibacterial activity of the Ag colloid was studied by disc diffusion method.

  1. Anti-bacterial Studies of Silver Nanoparticles

    CERN Document Server

    Theivasanthi, T

    2011-01-01

    We discuss about the antibacterial activities of Silver nanoparticles and compare them on both Gram negative and Gram positive bacteria in this investigation. The activities of Silver nanoparticles synthesized by electrolysis method are more in Gram (-) than Gram (+) bacteria. First time, we increase its antibacterial activities by using electrical power while on electrolysis synthesis and it is confirmed from its more antibacterial activities (For Escherichia coli bacteria). We investigate the changes of inner unit cell Lattice constant of Silver nanoparticles prepared in two different methods and its effects on antibacterial activities. We note that slight change of the lattice constant results in the enhancement of its antibacterial activities.

  2. Fluorophilia: Fluorophore-containing compounds adhere non-specifically to injured neurons

    Science.gov (United States)

    Hawkins, Bridget E.; Frederickson, Christopher J.; DeWitt, Douglas S.; Prough, Donald S.

    2012-01-01

    Ionic (free) zinc (Zn2+) is implicated in apoptotic neuronal degeneration and death. In our attempt to examine the effects of Zn2+ in neurodegeneration following brain injury, we serendipitously discovered that injured neurons bind fluorescein moieties, either alone or as part of an indicator dye, in histologic sections. This phenomenon, that we have termed “fluorophilia”, is analogous to the ability of degenerating neuronal somata and axons to bind silver ions (argyrophilia — the basis of silver degeneration stains). To provide evidence that fluorophilia occurs in sections of brain tissue, we used a wide variety of indicators such as Fluoro-Jade (FJ), a slightly modified fluorescein sold as a marker for degenerating neurons; Newport Green, a fluorescein-containing Zn2+ probe; Rhod-5N, a rhodamine-containing Ca2+ probe; and plain fluorescein. All yielded remarkably similar staining of degenerating neurons in the traumatic brain-injured tissue with the absence of staining in our sham-injured brains. Staining of presumptive injured neurons by these agents was not modified when Zn2+ in the brain section was removed by prior chelation with EDTA or TPEN, whereas staining by a non-fluorescein containing Zn2+ probe, N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ), was suppressed by prior chelation. Thus, certain fluorophore-containing compounds nonspecifically stain degenerating neuronal tissue in histologic sections and may not reflect the presence of Zn2+. This may be of concern to researchers using indicator dyes to detect metals in brain tissue sections. Further experiments may be advised to clarify whether Zn2+-binding dyes bind more specifically in intact neurons in culture or organotypic slices. PMID:22137653

  3. Biogenic silver nanoparticles associated with silver chloride nanoparticles (Ag@AgCl) produced by laccase from Trametes versicolor

    OpenAIRE

    Duran N; Cuevas R.; Cordi L.; Rubilar O.; Diez M.C.

    2014-01-01

    In the present study, semi-purified laccase from Trametes versicolor was applied for the synthesis of silver nanoparticles, and the properties of the produced nanoparticles were characterized. All of the analyses of the spectra indicated silver nanoparticle formation. A complete characterization of the silver nanoparticles showed that a complex of silver nanoparticles and silver ions was produced, with the majority of the particles having a Ag(2+) chemical structure. A hypothetical mechanisti...

  4. Coculture of rat embryonic proprioceptive sensory neurons and myotubes

    NARCIS (Netherlands)

    Copray, S; Liem, R; MantinghOtter, [No Value; Brouwer, N

    1996-01-01

    With the aim to study the cellular mechanisms underlying the process of muscle spindle (re)generation, dorsal root ganglia (DRG) neurons derived from 16-day rat embryos were cocultured with developing myotubes in a compartmentalized culture device. To accomplish the selective survival and neurite

  5. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  6. Discovery of ionic silver in silver nanoparticle suspension fabricated by arc discharge method

    Energy Technology Data Exchange (ETDEWEB)

    Tien, D.-C. [Graduate Institute of Mechanical and Electrical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan (China)], E-mail: s3408508@ntut.edu.tw; Tseng, K.-H.; Liao, C.-Y.; Huang, J.-C. [Department of Electrical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan (China); Tsung, T.-T. [Graduate Institute of Mechanical and Electrical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan (China)

    2008-09-08

    As a result of mankind's over-reliance on antibiotics, germs are becoming more drug-resistant every year. The gradual but inexorable decline in the efficacy of traditional antibiotics is forcing scientists and doctors to search for new weapons in the fight against germs. Metallic silver nanoparticle (Ag{sup 0}) and ionic silver (Ag{sup +}) are the future of the post-antibiotic era, with the latter playing perhaps the central role in this fight. Using the arc discharge method (ADM), our research has allowed us to fabricate silver nanoparticle suspension (SNPS) in deionized water with no added surfactants. Most related research in this field is confined to explore the composition of nanoparticle, ignoring ions. However, we aim to identify and measure the proportion of ionic silver in ADM-SNPS, using conductivity meters, centrifuges, titrator, and atomic absorption spectrophotometer (AA). The results of our experiments show that SNPS fabricated by means of ADM with no added surfactants contains metallic silver nanoparticle and ionic silver. The fabrication consumes silver rods at a rate of 100 mg/min, yielding metallic silver nanoparticle and ionic silver with concentrations of approximately 11 ppm and 19 ppm, respectively.

  7. Certain Aspects of Silver and Silver Nanoparticles in Wound Care: A Minireview

    Directory of Open Access Journals (Sweden)

    Marek Konop

    2016-01-01

    Full Text Available Resistance to antimicrobial agents by pathogenic bacteria has emerged in recent years and is a major health problem. In this context silver and silver nanoparticles (AgNP have been known to have inhibitory and bactericidal effects and was used throughout history for treatment of skin ulcer, bone fracture, and supporting wound healing. In all of these applications prevention and treatment of bacterial colonized/infected wounds are critical. In this context silver and its derivatives play an important role in health care. Silver is widely used in clinical practice in the form of silver nitrate and/or silver sulfadiazine. In the last few years silver nanoparticles entered into clinical practice as both antimicrobial and antifungal agents. In addition, nanosilver is used in coating medical devices (catheters and as component of wound dressings. In this paper we present summarized information about silver and nanoparticles made of silver in the context of their useful properties, especially antibacterial ones, being of a great interest for researchers and clinicians.

  8. Ultrastructural localization of silver in rat testis and organ distribution of radioactive silver in the rat

    DEFF Research Database (Denmark)

    Ernst, E; Rungby, J; Baatrup, E

    1992-01-01

    The deposition of silver after a single intravenous injection (2 micrograms Ag g-1 body weight) was studied in the testes of Wistar rats 24 h and 1 and 2 weeks after dosing with radiolabelled 110AgNo3 (2 micrograms Ag and 1.2 kBq g-1 body weight). Also, the temporal accumulation of silver during...... the experimental period was monitored in the blood, testes, epididymides, kidney, liver and brain. The subcellular distribution of silver within the testes was demonstrated by using the histochemical technique of autometallography. Silver was cleared rapidly from the blood. After an initial rise, concentrations...

  9. Functional dissociation in sweet taste receptor neurons between and within taste organs of Drosophila.

    Science.gov (United States)

    Thoma, Vladimiros; Knapek, Stephan; Arai, Shogo; Hartl, Marion; Kohsaka, Hiroshi; Sirigrivatanawong, Pudith; Abe, Ayako; Hashimoto, Koichi; Tanimoto, Hiromu

    2016-02-19

    Finding food sources is essential for survival. Insects detect nutrients with external taste receptor neurons. Drosophila possesses multiple taste organs that are distributed throughout its body. However, the role of different taste organs in feeding remains poorly understood. By blocking subsets of sweet taste receptor neurons, we show that receptor neurons in the legs are required for immediate sugar choice. Furthermore, we identify two anatomically distinct classes of sweet taste receptor neurons in the leg. The axonal projections of one class terminate in the thoracic ganglia, whereas the other projects directly to the brain. These two classes are functionally distinct: the brain-projecting neurons are involved in feeding initiation, whereas the thoracic ganglia-projecting neurons play a role in sugar-dependent suppression of locomotion. Distinct receptor neurons for the same taste quality may coordinate early appetitive responses, taking advantage of the legs as the first appendages to contact food.

  10. Cajal's contribution to the knowledge of the neuronal cell nucleus.

    Science.gov (United States)

    Lafarga, Miguel; Casafont, Iñigo; Bengoechea, Rocio; Tapia, Olga; Berciano, Maria T

    2009-08-01

    In 1906, the Spanish neurobiologist Santiago Ramón y Cajal was awarded the Nobel Prize in Physiology or Medicine in recognition of his work on the structure of neurons and their connections. Cajal is commonly regarded as the father of modern neuroscience. What is less well known is that Cajal also had a great interest in intracellular neuronal structures and developed the reduced silver nitrate method for the study of neurofibrils (neurofilaments) and nuclear subcompartments. It was in 1903 that Cajal discovered the "accessory body" ("Cajal body") and seven years later, published an article on the organization of the cell nucleus in mammalian neurons that represents a masterpiece of nuclear structure at the light microscopy level. In addition to the accessory body, it includes the analysis of several nuclear components currently recognized as fibrillar centers of the nucleolus, nuclear speckles of splicing factors, transcription foci, nuclear matrix, and the double nuclear membrane. The aim of this article is to revisit Cajal's contributions to the knowledge of the neuronal nucleus in light of our current understanding of nuclear structure and function.

  11. Methamphetamine Causes Degeneration of Dopamine Cell Bodies and Terminals of the Nigrostriatal Pathway Evidenced by Silver Staining

    Science.gov (United States)

    Ares-Santos, Sara; Granado, Noelia; Espadas, Isabel; Martinez-Murillo, Ricardo; Moratalla, Rosario

    2014-01-01

    Methamphetamine is a widely abused illicit drug. Recent epidemiological studies showed that methamphetamine increases the risk for developing Parkinson's disease (PD) in agreement with animal studies showing dopaminergic neurotoxicity. We examined the effect of repeated low and medium doses vs single high dose of methamphetamine on degeneration of dopaminergic terminals and cell bodies. Mice were given methamphetamine in one of the following paradigms: three injections of 5 or 10 mg/kg at 3 h intervals or a single 30 mg/kg injection. The integrity of dopaminergic fibers and cell bodies was assessed at different time points after methamphetamine by tyrosine hydroxylase immunohistochemistry and silver staining. The 3 × 10 protocol yielded the highest loss of striatal dopaminergic terminals, followed by the 3 × 5 and 1 × 30. Some degenerating axons could be followed from the striatum to the substantia nigra pars compacta (SNpc). All protocols induced similar significant degeneration of dopaminergic neurons in the SNpc, evidenced by amino-cupric-silver-stained dopaminergic neurons. These neurons died by necrosis and apoptosis. Methamphetamine also killed striatal neurons. By using D1-Tmt/D2-GFP BAC transgenic mice, we observed that degenerating striatal neurons were equally distributed between direct and indirect medium spiny neurons. Despite the reduced number of dopaminergic neurons in the SNpc at 30 days after treatment, there was a partial time-dependent recovery of dopamine terminals beginning 3 days after treatment. Locomotor activity and motor coordination were robustly decreased 1–3 days after treatment, but recovered at later times along with dopaminergic terminals. These data provide direct evidence that methamphetamine causes long-lasting loss/degeneration of dopaminergic cell bodies in the SNpc, along with destruction of dopaminergic terminals in the striatum. PMID:24169803

  12. Silver-hafnium braze alloy

    Science.gov (United States)

    Stephens, Jr., John J.; Hosking, F. Michael; Yost, Frederick G.

    2003-12-16

    A binary allow braze composition has been prepared and used in a bonded article of ceramic-ceramic and ceramic-metal materials. The braze composition comprises greater than approximately 95 wt % silver, greater than approximately 2 wt % hafnium and less than approximately 4.1 wt % hafnium, and less than approximately 0.2 wt % trace elements. The binary braze alloy is used to join a ceramic material to another ceramic material or a ceramic material, such as alumina, quartz, aluminum nitride, silicon nitride, silicon carbide, and mullite, to a metal material, such as iron-based metals, cobalt-based metals, nickel-based metals, molybdenum-based metals, tungsten-based metals, niobium-based metals, and tantalum-based metals. A hermetic bonded article is obtained with a strength greater than 10,000 psi.

  13. Cadmium hazard in silver brazing.

    Science.gov (United States)

    Gan, S L; Tan, S H; Pinnagoda, J; Tan, K T

    1995-03-01

    This study evaluates the usage of cadmium-containing silver brazing alloys in Singapore and the potential cadmium hazard from its use. Of the 137 factories which responded to the survey questionnaire, only 28 (20.4%) carried out brazing. Of these, only 7 factories used cadmium-containing filler alloys. One hundred and six out of 123 workers from one of these factories had cadmium-in-blood concentrations exceeding 10 mcg/l. Thirty-one (29.2%) of the workers with excessive cadmium absorption had urinary beta-2 microglobulin levels exceeding 28 mcg/g creat. Workers in the other factories who were intermittently exposed had cadmium-in-blood concentrations of 10 mcg/l and below.

  14. Tuning Properties in Silver Clusters

    KAUST Repository

    Joshi, Chakra Prasad

    2015-07-09

    The properties of Ag nanoclusters are not as well understood as those of their more precious Au cousins. However, a recent surge in the exploration of strategies to tune the physicochemical characteristics of Ag clusters addresses this imbalance, leading to new insights into their optical, luminescence, crystal habit, metal-core, ligand-shell and environmental properties. In this Perspective, we provide an overview of the latest strategies along with a brief introduction of the theoretical framework necessary to understand the properties of silver nanoclusters and the basis for their tuning. The advances in cluster research and the future prospects presented in this Perspective will eventually guide the next large systematic study of nanoclusters, resulting in a single collection of data similar to the periodic table of elements.

  15. Identification of embryonic stem cell-derived midbrain dopaminergic neurons for engraftment.

    Science.gov (United States)

    Ganat, Yosif M; Calder, Elizabeth L; Kriks, Sonja; Nelander, Jenny; Tu, Edmund Y; Jia, Fan; Battista, Daniela; Harrison, Neil; Parmar, Malin; Tomishima, Mark J; Rutishauser, Urs; Studer, Lorenz

    2012-08-01

    Embryonic stem cells (ESCs) represent a promising source of midbrain dopaminergic (DA) neurons for applications in Parkinson disease. However, ESC-based transplantation paradigms carry a risk of introducing inappropriate or tumorigenic cells. Cell purification before transplantation may alleviate these concerns and enable identification of the specific DA neuron stage most suitable for cell therapy. Here, we used 3 transgenic mouse ESC reporter lines to mark DA neurons at 3 stages of differentiation (early, middle, and late) following induction of differentiation using Hes5::GFP, Nurr1::GFP, and Pitx3::YFP transgenes, respectively. Transplantation of FACS-purified cells from each line resulted in DA neuron engraftment, with the mid-stage and late-stage neuron grafts being composed almost exclusively of midbrain DA neurons. Mid-stage neuron cell grafts had the greatest amount of DA neuron survival and robustly induced recovery of motor deficits in hemiparkinsonian mice. Our data suggest that the Nurr1+ stage (middle stage) of neuronal differentiation is particularly suitable for grafting ESC-derived DA neurons. Moreover, global transcriptome analysis of progeny from each of the ESC reporter lines revealed expression of known midbrain DA neuron genes and also uncovered previously uncharacterized midbrain genes. These data demonstrate remarkable fate specificity of ESC-derived DA neurons and outline a sequential stage-specific ESC reporter line paradigm for in vivo gene discovery.

  16. Bactericidal performance of visible-light responsive titania photocatalyst with silver nanostructures.

    Directory of Open Access Journals (Sweden)

    Ming-Show Wong

    Full Text Available BACKGROUND: Titania dioxide (TiO(2 photocatalyst is primarily induced by ultraviolet light irradiation. Visible-light responsive anion-doped TiO(2 photocatalysts contain higher quantum efficiency under sunlight and can be used safely in indoor settings without exposing to biohazardous ultraviolet light. The antibacterial efficiency, however, remains to be further improved. METHODOLOGY/PRINCIPAL FINDINGS: Using thermal reduction method, here we synthesized silver-nanostructures coated TiO(2 thin films that contain a high visible-light responsive antibacterial property. Among our tested titania substrates including TiO(2, carbon-doped TiO(2 [TiO(2 (C] and nitrogen-doped TiO(2 [TiO(2 (N], TiO(2 (N showed the best performance after silver coating. The synergistic antibacterial effect results approximately 5 log reductions of surviving bacteria of Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus and Acinetobacter baumannii. Scanning electron microscope analysis indicated that crystalline silver formed unique wire-like nanostructures on TiO(2 (N substrates, while formed relatively straight and thicker rod-shaped precipitates on the other two titania materials. CONCLUSION/SIGNIFICANCE: Our results suggested that proper forms of silver on various titania materials could further influence the bactericidal property.

  17. Silver (nano)materials cause genotoxicity in Enchytraeus crypticus, as determined by the comet assay.

    Science.gov (United States)

    Maria, Vera L; Ribeiro, Maria João; Guilherme, Sofia; Soares, Amadeu M V M; Scott-Fordsmand, Janeck J; Amorim, Mónica J B

    2017-08-10

    Enchytraeids have been used in standard ecotoxicity testing for approximately 20 yr. Since adopting the standard test for survival and reproduction, a number of additional tools have been developed, including transcriptomics and enzymatic biomarkers. So far, a genotoxicity tool and endpoint have not been used; hence, the goals of the present study included optimization of the in vivo alkaline comet assay in Enchytraeus crypticus. Further, the effect of silver nanomaterial (Ag NM300K, dispersed, 15 nm) was tested and compared with silver nitrate. Hydrogen peroxide was used as a positive control. The various steps were optimized. The fully detailed standard operating procedure is presented. Silver materials caused genotoxicity, this being differentiated for the nano and non-nano forms. Silver nitrate caused genotoxicity after 3 d of exposure in a dose-related manner, although after 7 d the effects were either reduced or repaired. Ag NM300K caused higher genotoxicity after 7 d for the lowest concentration, highlighting a potential nonmonotonic dose-response effect. Overall, the comet assay showed the power to discriminate effects between materials and also toxicity at low relevant doses. Environ Toxicol Chem 2017;9999:1-8. © 2017 SETAC. © 2017 SETAC.

  18. Study of ATM Phosphorylation by Cdk5 in Neuronal Cells.

    Science.gov (United States)

    She, Hua; Mao, Zixu

    2017-01-01

    The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. We previously showed that Cdk5 (cyclin-dependent kinase 5) is activated by DNA damage and directly phosphorylates ATM at serine 794 in postmitotic neurons. Phosphorylation at serine 794 precedes and is required for ATM autophosphorylation at serine 1981, and activates ATM kinase activity. Cdk5-ATM pathway plays a crucial role in DNA damage-induced neuronal injury. This chapter describes protocols used in analyzing ATM phosphorylation by Cdk5 in CGNs (cerebellar granule neurons) and its effects on neuronal survival.

  19. Sealed Cylindrical Silver/Zinc Batteries Project

    Data.gov (United States)

    National Aeronautics and Space Administration — RBC Technologies has significanly improved the cycle life and wet life of silver/zinc battery technology through novel separator and anode formulations. This...

  20. Silver nanoparticles – wolves in sheep's clothing?

    DEFF Research Database (Denmark)

    Foldbjerg, Rasmus; Jiang, Xiumei; Miclaus, Teodora

    2015-01-01

    Silver nanoparticles (Ag NPs) are one of the most widely utilized engineered nanomaterials (ENMs) in commercial products due to their effective antibacterial activity, high electrical conductivity, and optical properties. Therefore, they have been one of the most intensively investigated nanomate...

  1. Silver Sulfadiazine Nanosystems for Burn Therapy

    National Research Council Canada - National Science Library

    Venkataraman, Meenakshi; Nagarsenker, Mangal

    2013-01-01

    The objective of the present study was to formulate stable silver sulfadiazine (SSD) nanosuspensions and nanogels suitable for topical delivery with a view to increase bactericidal activity in burn therapy...

  2. Electrolytic silver ion cell sterilizes water supply

    Science.gov (United States)

    Albright, C. F.; Gillerman, J. B.

    1968-01-01

    Electrolytic water sterilizer controls microbial contamination in manned spacecraft. Individual sterilizer cells are self-contained and require no external power or control. The sterilizer generates silver ions which do not impart an unpleasant taste to water.

  3. Realistic Silver Optical Constants for Plasmonics

    Science.gov (United States)

    Jiang, Yajie; Pillai, Supriya; Green, Martin A.

    2016-07-01

    Silver remains the preferred conductor for optical and near-infrared plasmonics. Many high-profile studies focus exclusively on performance simulation in such applications. Almost invariably, these use silver optical data either from Palik’s 1985 handbook or, more frequently, an earlier Johnson and Christy (J&C) tabulation. These data are inconsistent, making it difficult to ascertain the reliability of the simulations. The inconsistency stems from challenges in measuring representative properties of pristine silver, due to tarnishing on air exposure. We demonstrate techniques, including use of silicon-nitride membranes, to access the full capabilities of multiple-angle, spectrometric-ellipsometry to generate an improved data set, representative of overlayer-protected, freshly-deposited silver films on silicon-nitride and glass.

  4. Silver nasal sprays: misleading Internet marketing.

    Science.gov (United States)

    Gaslin, Michael T; Rubin, Cory; Pribitkin, Edmund A

    2008-04-01

    Long-term use of silver-containing products is associated with a permanent bluish-gray discoloration of the skin known as argyria, but they remain widely available despite several measures by the FDA to regulate them. Several recent case reports have described the occurrence of argyria as a result of using these "natural" products. We used the five most common Internet search engines to find Web sites providing information on silver-containing nasal sprays. Of 49 Web sites analyzed, only 2 (4%) mentioned argyria as a possible complication, although 30 (61%) did caution against long-term use. Eight sites (16%) made specific claims about the health benefits of the product. All 49 sites (100%) provided direct or indirect links to buy silver-containing nasal sprays. We conclude that information about silver-containing nasal sprays on the Internet is misleading and inaccurate. Therefore, otolaryngologists should be aware of the misinformation their patients may be receiving about these products.

  5. Green synthesis of silver nanoparticles using tannins

    Science.gov (United States)

    Raja, Pandian Bothi; Rahim, Afidah Abdul; Qureshi, Ahmad Kaleem; Awang, Khalijah

    2014-09-01

    Colloidal silver nanoparticles were prepared by rapid green synthesis using different tannin sources as reducing agent viz. chestnut (CN), mangrove (MG) and quebracho (QB). The aqueous silver ions when exposed to CN, MG and QB tannins were reduced which resulted in formation of silver nanoparticles. The resultant silver nanoparticles were characterized using UV-Visible, X-ray diffraction (XRD), scanning electron microscopy (SEM/EDX), and transmission electron microscopy (TEM) techniques. Furthermore, the possible mechanism of nanoparticles synthesis was also derived using FT-IR analysis. Spectroscopy analysis revealed that the synthesized nanoparticles were within 30 to 75 nm in size, while XRD results showed that nanoparticles formed were crystalline with face centered cubic geometry.

  6. Clinical spectrum of silver - Russell syndrome

    Directory of Open Access Journals (Sweden)

    Sapna N.K. Varma

    2013-01-01

    Full Text Available Silver - Russell syndrome is a clinically and genetically heterogenous condition characterized by severe intrauterine and postnatal growth retardation, craniofacial disproportion and normal intelligence downward curvature of the corner of the mouth, syndactyly and webbed fingers. Diagnosis of Silver - Russell syndrome remains clinical; no definite etiology or specific tests have been established. In the recent years, it has been shown that more than 38% of patients have hypomethylation in the imprinting control region 1 of 11p15 and one-tenth of patients carry a maternal uniparental disomy of chromosome seven. The pathophysiological mechanisms resulting in the Silver - Russell phenotype remain unknown despite the recent progress in deciphering the molecular defects associated with this condition. This case report describes the clinical features of Silver - Russell syndrome in a father and daughter.

  7. Elastocapillary assembly of silver nanotube forest

    Science.gov (United States)

    Yang, Xin; Pack, Min; Sun, Ying

    2014-11-01

    Nanorods/nanotubes have large surface areas making them promising for applications such as high-performance battery and capacitor electrodes, photovoltaics, and interconnects. In this study, we demonstrate the formation of 3D microarchitectures via elastocapillary self-assembly of silver nanotube forests. Patterned silver nanotube forests of different lengths and diameters are made by inkjet printing of silver nanoinks into nanoporous anodic aluminum oxide membranes. These silver nanotube forests are then self-assembled into ordered microstructures via capillary forces induced by liquid condensation, which is compared with immersing nanotubes directly into a liquid. The effects of length, diameter, and footprint of the nanotube forest on self-assembled patterns are systematically studied. By decreasing the footprint and/or increasing the length of nanotube forest, the stiffness of the nanotube forest decreases, bringing the nanotubes together to form closely packed microstructures.

  8. Genetics Home Reference: Russell-Silver syndrome

    Science.gov (United States)

    ... T, Spengler S, Gogiel M, Begemann M, Elbracht M. Epigenetic and genetic diagnosis of Silver-Russell syndrome. Expert ... PubMed More from Genetics Home Reference Bulletins Rare Disease Day 2018 Darwin Day 2018 February is Age- ...

  9. Anaerobic Toxicity of Cationic Silver Nanoparticles

    Data.gov (United States)

    U.S. Environmental Protection Agency — Toxicity data for the impact of nano-silver on anaerobic degradation. This dataset is associated with the following publication: Gitipour, A., S. Thiel, K. Scheckel,...

  10. Tartu on Eesti Boston / Silver Meikar

    Index Scriptorium Estoniae

    Meikar, Silver, 1978-

    2007-01-01

    Tartu eeldustest kujuneda hariduse, innovaatilise tootmise, pärimuskultuuri ja linnaruumi tasakaalustatud kasutamise südameks. Ettevõtluse, transpordi ja turismi arengust. Lisa: Silver Meikari Lõuna-Eesti edu top 10

  11. The preparation of silver nanoparticle decorated silica nanowires on fused quartz as reusable versatile nanostructured surface-enhanced Raman scattering substrates.

    Science.gov (United States)

    Hwang, Jih-Shang; Chen, Kuan-Yu; Hong, Shih-Jay; Chen, Shih-Wei; Syu, Wun-Shing; Kuo, Chi-Wen; Syu, Wei-Yi; Lin, Tai Yuan; Chiang, Hai-Pang; Chattopadhyay, Surojit; Chen, Kuei-Hsien; Chen, Li-Chyong

    2010-01-15

    We introduce a platform, comprised of silver nanoparticle decorated silica nanowires (SiONWs) dispersed on fused quartz substrates, for high sensitivity surface-enhanced Raman scattering (SERS) measurements using both frontal (through the analytes) and back-face (through the transparent substrate) excitation. Quasi-quantitative SERS performances on the specialized substrate, vis-à-vis a silver deposited bare fused quartz plate, showed: (i) the suitability of the Ag modified SiONW substrate for frontal as well as back-face excitation; (ii) a wider detection range with high sensitivity to Rhodamine 6G; and (iii) good underwater metal-oxide adhesion of the specialized substrates. Capable of surviving ultrasonic cleaning, the substrate introduced is one of the few reusable low-cost Ag-based nanostructured SERS substrates, requiring only a simple silver reload process (the silver mirror reaction).

  12. Sprouting ability and biomass production of downy and silver birch stumps of different diameters

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Tord [Department of Bioenergy, Swedish University of Agricultural Sciences, SE-750 07 Uppsala (Sweden)

    2008-10-15

    The aim of this study was to compare the sprouting ability of stumps of different diameters of downy (Betula pubescens Ehrh.) and silver (Betula pendula Roth) birch. The number of living stumps, and the number and height of sprouts were recorded annually and the biomass of the sprouts was calculated. Two hundred naturally regenerated downy and silver birches were examined. These were part of a commercial cleaning in late August 1983, which left 20-cm-high stumps. The experimental site was located on forest land in central Sweden (latitude 60 15'N, longitude 16 01'E). The stumps were categorised into four diameter classes: 10-19, 20-29, 30-39 and 40-50 mm. The site was examined in September of the year after cutting and on a number of occasions up to 9 years after cutting. The number of living stumps of each species was recorded. When the sprouts were 9 years old, their diameter at breast height was recorded. Then, the sprouts were cut and stems and branches were dried and weighted. After 1 and 9 years, the percentage of surviving downy birch stumps was 90% and 61%, respectively. The equivalent figures for silver birch were 82% and 55%. The number of sprouts per stump differed significantly between the species and the stump diameter classes. The greatest mean number of downy birch sprouts per stump (2.8{+-}0.3) was for the diameter class 40-50 mm, and for silver birch sprouts (2.3{+-}0.2), for the 30-39 mm stumps. The diameter at breast height, height and weight of individual sprouts 9 years after cutting were significantly different between downy and silver birches and the diameter classes. The mean downy birch sprout weight (1.00{+-}0.01 kg d.w. stump{sup -1}) varied between diameter classes and the heaviest sprout weight (1.18{+-}0.02 kg d.w. stump{sup -1}) was produced by 30-39 mm stumps. The heaviest silver birch sprout, 1.94{+-}0.04 kg d.w., was also produced by 40-50 mm stumps. The mean weight was 1.55{+-}0.05 kg d.w. The sprout biomass per living

  13. Nano-silver in drinking water and drinking water sources: stability and influences on disinfection by-product formation.

    Science.gov (United States)

    Tugulea, A-M; Bérubé, D; Giddings, M; Lemieux, F; Hnatiw, J; Priem, J; Avramescu, M-L

    2014-10-01

    untreated Ottawa River water, with a dissolved organic carbon concentration of 6 mg/L, was significantly higher than the stability of the nano-silver dispersions in distilled, organic-free water. Nano-silver particles suspended in the groundwater agglomerated and were quickly and quantitatively removed from the solution. Our data confirm previous observations that natural dissolved organic matter stabilizes nano-silver particles, while the high-ionic strength of groundwater appears to favor their agglomeration and precipitation. As expected, nano-silver was not stable in Ottawa River water through the chlorination process, but survived for many days when added to the Ottawa River water after treatment with chlorine or chloramines. Stirring appeared to have minimal effect on nano-silver stability in untreated and treated Ottawa River water. The profile of DBPs formed in the presence of nAg differed significantly from the profile of DBPs formed in the absence of nAg only at the 1 mg/L nAg concentration. The differences observed consisted mainly in reduced formation of some brominated DBPs and a small increase in the formation of cyanogen chloride. The reduced formation of brominated congeners may be explained by the decrease in available bromide due to the presence of Ag(+) ions. It should be noted that a concentration of 1 mg/L is significantly higher than nAg concentrations that would be expected to be present in surface waters, but these results could be significant for the disinfection of some wastewaters with comparably high nano-silver concentrations.

  14. Action of glucocorticoids on survival of nerve cells : Promoting neurodegeneration or neuroprotection?

    NARCIS (Netherlands)

    Abraham, I.; Harkany, T.; Horvath, K.M.; Luiten, P.G.M.

    Extensive studies during the past decades provided compelling evidence that glucocorticoids (GCs) have the potential to affect the development, survival and death of neurones. These observations, however, reflect paradoxical features of GCs, as they may be critically involved in both

  15. Biosynthesis Of Silver Nanoparticles From Marine Seaweed Sargassum Cinereum And Their Antibacterial Activity

    Digital Repository Service at National Institute of Oceanography (India)

    Mohandass, C.; VijayRaj, A.S.; Rajasabapathy, R.; SatheeshBabu, S.; Rao, S.V.; Shiva, C.; De-Mello, I.

    Seaweed extracts of Sargassum cinereum was used as a reducing agent in the eco-friendly extracellular synthesis of silver nanoparticles from an aqueous solution of silver nitrate (AgNO3 ). High conversion of silver ions to silver nanoparticles...

  16. Gold and Silver Extraction from Leach Solutions

    Directory of Open Access Journals (Sweden)

    Bagdaulet K. Kenzhaliyev

    2014-03-01

    Full Text Available There has been carried out an investigation on the extraction of gold and silver from thiosulfate solutions: standard test and technological solutions of chemical and electrochemical leaching. The influence of related metals on the process of extracting gold from solution was studied. There has been conducted a comparative study of the IR spectra of solutions after the sorption of gold, silver and related metals.

  17. Electrocatalytic activity of bismuth doped silver electrodes

    CERN Document Server

    Amjad, M

    2002-01-01

    Investigation of redox reactions on silver, and bismuth doped silver electrodes in aqueous KOH solutions, by using potentiostatic steady-state polarization technique, has been carried out. The redox wave potential and current displacements along with multiplicity of the latter have been examined. These electrodes were employed for the oxidation of organic molecules such as ethylamine in alkaline media. Subsequently, these electrodes were ranked with respect to their activity for the redox reactions. (author)

  18. Realistic Silver Optical Constants for Plasmonics

    OpenAIRE

    Yajie Jiang; Supriya Pillai; Green, Martin A.

    2016-01-01

    Silver remains the preferred conductor for optical and near-infrared plasmonics. Many high-profile studies focus exclusively on performance simulation in such applications. Almost invariably, these use silver optical data either from Palik?s 1985 handbook or, more frequently, an earlier Johnson and Christy (J&C) tabulation. These data are inconsistent, making it difficult to ascertain the reliability of the simulations. The inconsistency stems from challenges in measuring representative prope...

  19. Analysis of normal and transparent silver Teflon

    Science.gov (United States)

    Stuckey, W. K.; Galuska, A. A.; Uht, J.

    1985-01-01

    Samples of Inconel/silver/Teflon exposed to solar radiation, and atomic oxygen on Solar Max were microcharacterized. Those samples exposed to atomic oxygen from the metallic side had become transparent while those exposed from the Teflon side remained reflective. The difference between the transparent and non-transparent material was determined. Microcharacterization of these Inconel/silver/Teflon samples was performed using scanning electron microscopy with windowless energy dispersive X ray analysis, secondary ion mass spectrometry, and X ray photoelectron spectroscopy.

  20. Selective Electroless Silver Deposition on Graphene Edges

    DEFF Research Database (Denmark)

    Durhuus, D.; Larsen, M. V.; Andryieuski, Andrei

    2015-01-01

    We demonstrate a method of electroless selective silver deposition on graphene edges or between graphene islands without covering the surface of graphene. Modifications of the deposition recipe allow for decoration of graphene edges with silver nanoparticles or filling holes in damaged graphene...... on silica substrate and thus potentially restoring electric connectivity with minimal influence on the overall graphene electrical and optical properties. The presented technique could find applications in graphene based transparent conductors as well as selective edge functionalization and can be extended...

  1. In vitro percutaneous penetration and characterization of silver from silver-containing textiles.

    Science.gov (United States)

    Bianco, Carlotta; Kezic, Sanja; Crosera, Matteo; Svetličić, Vesna; Šegota, Suzana; Maina, Giovanni; Romano, Canzio; Larese, Francesca; Adami, Gianpiero

    2015-01-01

    The objective of this study was to determine the in vitro percutaneous penetration of silver and characterize the silver species released from textiles in different layers of full thickness human skin. For this purpose, two different wound dressings and a garment soaked in artificial sweat were placed in the donor compartments of Franz cells for 24 hours. The concentration of silver in the donor phase and in the skin was determined by an electrothermal atomic absorption spectrometer (ET-AAS) and by inductively coupled plasma mass spectrometer (ICP-MS). The characterization of silver species in the textiles and in the skin layers was made by scanning electron microscopy with integrated energy dispersive X-ray spectroscopy (SEM-EDX). Additionally, the size distribution of silver nanoparticles in the textiles was performed by atomic force microscopy (AFM). On the surface of all investigated materials, silver nanoparticles of different size and morphology were found. Released silver concentrations in the soaking solutions (ie, exposure concentration) ranged from 0.7 to 4.7 μg/mL (0.6-4.0 μg/cm(2)), fitting the bactericidal range. Silver and silver chloride aggregates at sizes of up to 1 μm were identified both in the epidermis and dermis. The large size of these particles suggests that the aggregation occurred in the skin. The formation of these aggregates likely slowed down the systemic absorption of silver. Conversely, these aggregates may form a reservoir enabling prolonged release of silver ions, which might lead to local effects.

  2. Engineered Escherichia coli silver-binding periplasmic protein that promotes silver tolerance.

    Science.gov (United States)

    Sedlak, Ruth Hall; Hnilova, Marketa; Grosh, Carolynn; Fong, Hanson; Baneyx, Francois; Schwartz, Dan; Sarikaya, Mehmet; Tamerler, Candan; Traxler, Beth

    2012-04-01

    Silver toxicity is a problem that microorganisms face in medical and environmental settings. Through exposure to silver compounds, some bacteria have adapted to growth in high concentrations of silver ions. Such adapted microbes may be dangerous as pathogens but, alternatively, could be potentially useful in nanomaterial-manufacturing applications. While naturally adapted isolates typically utilize efflux pumps to achieve metal resistance, we have engineered a silver-tolerant Escherichia coli strain by the use of a simple silver-binding peptide motif. A silver-binding peptide, AgBP2, was identified from a combinatorial display library and fused to the C terminus of the E. coli maltose-binding protein (MBP) to yield a silver-binding protein exhibiting nanomolar affinity for the metal. Growth experiments performed in the presence of silver nitrate showed that cells secreting MBP-AgBP2 into the periplasm exhibited silver tolerance in a batch culture, while those expressing a cytoplasmic version of the fusion protein or MBP alone did not. Transmission electron microscopy analysis of silver-tolerant cells revealed the presence of electron-dense silver nanoparticles. This is the first report of a specifically engineered metal-binding peptide exhibiting a strong in vivo phenotype, pointing toward a novel ability to manipulate bacterial interactions with heavy metals by the use of short and simple peptide motifs. Engineered metal-ion-tolerant microorganisms such as this E. coli strain could potentially be used in applications ranging from remediation to interrogation of biomolecule-metal interactions in vivo.

  3. Kappe neurons, a novel population of olfactory sensory neurons

    Science.gov (United States)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  4. Lumping Izhikevich neurons

    Directory of Open Access Journals (Sweden)

    Visser Sid

    2014-12-01

    Full Text Available We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behavior intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting Izhikevich neurons. In both cases, the lumped model is compared with the spiking network. There is excellent agreement in terms of duration and number of action potentials within the bursts, but there is a slight mismatch of the burst frequency. The lumped model accurately accounts for both intrinsic bursting and post inhibitory rebound potentials in the neuron model, features which are absent in prevalent neural mass models.

  5. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  6. Imaging voltage in neurons

    Science.gov (United States)

    Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael

    2011-01-01

    In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles and intrinsic approaches), and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic or electro-optical phenomena, to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods. PMID:21220095

  7. Coconut oil attenuates the effects of amyloid-β on cortical neurons in vitro.

    Science.gov (United States)

    Nafar, Firoozeh; Mearow, Karen M

    2014-01-01

    Dietary supplementation has been studied as an approach to ameliorating deficits associated with aging and neurodegeneration. We undertook this pilot study to investigate the effects of coconut oil supplementation directly on cortical neurons treated with amyloid-β (Aβ) peptide in vitro. Our results indicate that neuron survival in cultures co-treated with coconut oil and Aβ is rescued compared to cultures exposed only to Aβ. Coconut oil co-treatment also attenuates Aβ-induced mitochondrial alterations. The results of this pilot study provide a basis for further investigation of the effects of coconut oil, or its constituents, on neuronal survival focusing on mechanisms that may be involved.

  8. Spatial learning depends on both the addition and removal of new hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    David Dupret

    2007-08-01

    Full Text Available The role of adult hippocampal neurogenesis in spatial learning remains a matter of debate. Here, we show that spatial learning modifies neurogenesis by inducing a cascade of events that resembles the selective stabilization process characterizing development. Learning promotes survival of relatively mature neurons, apoptosis of more immature cells, and finally, proliferation of neural precursors. These are three interrelated events mediating learning. Thus, blocking apoptosis impairs memory and inhibits learning-induced cell survival and cell proliferation. In conclusion, during learning, similar to the selective stabilization process, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons.

  9. Activity of Antimicrobial Silver Polystyrene Nanocomposites

    Directory of Open Access Journals (Sweden)

    M. Palomba

    2012-01-01

    Full Text Available A simple technique based on doping polymers with in situ generated silver nanoparticles (Ag/PS films has been developed. In particular, an antiseptic material has been prepared by dissolving silver 1,5-cyclooctadiene-hexafluoroacetylacetonate in amorphous polystyrene, and the obtained solid solution has been heated for ca. 10 s at a convenient temperature (180°C. Under such conditions the metal precursor decomposes producing silver atoms that diffuse into the polymer and clusterize. The antimicrobial characteristics of the resulting polystyrene-based material have been accurately evaluated toward Escherichia coli (E. coli comparing the cytotoxicity effect of 10 wt.% and 30 wt.% (drastic and mild annealing silver-doped polystyrene to the corresponding pure micrometric silver powder. Two different bacterial viability assays were performed in order to demonstrate the cytotoxic effect of Ag/PS films on cultured E. coli: (1 turbidimetric determination of optical density; (2 BacLight fluorescence-based test. Both methods have shown that silver-doped polystyrene (30 wt.% provides higher antibacterial activity than pure Ag powder, under similar concentration and incubation conditions.

  10. Silver As Antibacterial toward Listeria monocytogenes.

    Science.gov (United States)

    Belluco, Simone; Losasso, Carmen; Patuzzi, Ilaria; Rigo, Laura; Conficoni, Daniele; Gallocchio, Federica; Cibin, Veronica; Catellani, Paolo; Segato, Severino; Ricci, Antonia

    2016-01-01

    Listeria monocytogenes is a serious foodborne pathogen that can contaminate food during processing and can grow during food shelf-life. New types of safe and effective food contact materials embedding antimicrobial agents, like silver, can play an important role in the food industry. The present work aimed at evaluating the in vitro growth kinetics of different strains of L. monocytogenes in the presence of silver, both in its ionic and nano form. The antimicrobial effect was determined by assaying the number of culturable bacterial cells, which formed colonies after incubation in the presence of silver nanoparticles (AgNPs) or silver nitrate (AgNO3). Ionic release experiments were performed in parallel. A different reduction of bacterial viability between silver ionic and nano forms was observed, with a time delayed effect exerted by AgNPs. An association between antimicrobial activity and ions concentration was shown by both silver chemical forms, suggesting the major role of ions in the antimicrobial mode of action.

  11. Emergence of Assortative Mixing between Clusters of Cultured Neurons

    Science.gov (United States)

    Teller, Sara; Granell, Clara; De Domenico, Manlio; Soriano, Jordi; Gómez, Sergio; Arenas, Alex

    2014-01-01

    The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons (clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, as well as a rich-club core, which shapes a ‘connectivity backbone’ in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture. PMID:25188377

  12. Glutamate gated spiking Neuron Model.

    Science.gov (United States)

    Deka, Krisha M; Roy, Soumik

    2014-01-01

    Biological neuron models mainly analyze the behavior of neural networks. Neurons are described in terms of firing rates viz an analog signal. The Izhikevich neuron model is an efficient, powerful model of spiking neuron. This model is a reduction of Hodgkin-Huxley model to a two variable system and is capable of producing rich firing patterns for many biological neurons. In this paper, the Regular Spiking (RS) neuron firing pattern is used to simulate the spiking of Glutamate gated postsynaptic membrane. Simulation is done in MATLAB environment for excitatory action of synapses. Analogous simulation of spiking of excitatory postsynaptic membrane potential is obtained.

  13. Photosensitive neurons in mollusks

    Directory of Open Access Journals (Sweden)

    Kartelija Gordana

    2005-01-01

    Full Text Available In addition to regular photoreceptors, some invertebrates possess simple extra ocular photoreceptors. For ex­ample, the central ganglia of mollusks contain photosensitive neurons. These neurons are located on the dorsal surface of the ganglia and based on their electrophysiological properties it has been postulated that they are internal photoreceptors. Besides the eye, transduction of light also occurs in these extra-ocular photoreceptors. In the present work, we analyze the reactivity of these nerve cells to light and describe the underlying mechanism mediating the light-induced response.

  14. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...

  15. Blood and Tissue Silver Levels Following Application of Silver-Based Dressings to Sulfur Mustard Chemical Burns.

    Science.gov (United States)

    Barillo, David J; Croutch, Claire R; Reid, Frances; Culley, Tara; Sosna, William; Roseman, Julie

    Silver-based dressings are commonly used in burn care. Silver sulfadiazine use is associated with elevated blood, urine, and tissue levels of silver ion. We examined wound and tissue levels of silver ion in a two-species model of sulfur mustard chemical burn injury treated with two different silver-based dressings. Superficial dermal and moderate thickness dermal chemical burns were induced in 16 hairless guinea pigs and in 16 Gottingen minipigs by exposure to sulfur mustard vapor. After debridement, silver-nylon burn dressings or silver-calcium alginate dressings were applied and changed every 7 days until wound healing or a maximum of 60 days post exposure. At autopsy, liver, spleen, and wound samples were harvested. Silver ion was measured using inductively coupled plasma-mass spectrography with a lower level of detection of 0.02 parts per billion. Negligible silver ion levels were found in the liver (mean burn wound dressings than with silver-calcium alginate dressings. Silver ion could be detected in some wounds 40 days after dressings were removed. In a chemical burn model, application of silver-nylon or silver-calcium alginate dressings is associated with elevated wound levels but negligible tissue levels of silver ion.

  16. Propagation of plasmons in designed single crystalline silver nanostructures

    DEFF Research Database (Denmark)

    Kumar, Shailesh; Lu, Ying-Wei; Huck, Alexander

    2012-01-01

    We demonstrate propagation of plasmons in single crystalline silver nanostructures fabricated using a combination of a bottom-up and a top-down approach. Silver nanoplates of thickness around 65 nm and a surface area of about 100 μm2 are made using a wet chemical method. Silver nanotips and nanow......We demonstrate propagation of plasmons in single crystalline silver nanostructures fabricated using a combination of a bottom-up and a top-down approach. Silver nanoplates of thickness around 65 nm and a surface area of about 100 μm2 are made using a wet chemical method. Silver nanotips...

  17. Silver Nanoparticles and Ionic Silver Have Opposite Effects on Spontaneous Activity and Pharmacological Responses in Neuronal Networks In Vitro

    Science.gov (United States)

    CONTROL ID: 1850472 CONTACT (NAME ONLY): Timothy Shafer Abstract Details PRESENTATION TYPE: Platform or Poster CURRENT CATEGORY: Nanotoxicology, In Vitro | Neurotoxicity, General | Neurotoxicity, Metals KEYWORDS: Nanoparticle, Neurotoxicity, microelectrode array. DATE/TIME LAST...

  18. Silver deposition on stainless steel container surfaces in contact with disinfectant silver aqueous solutions

    Science.gov (United States)

    Petala, M.; Tsiridis, V.; Mintsouli, I.; Pliatsikas, N.; Spanos, Th.; Rebeyre, P.; Darakas, E.; Patsalas, P.; Vourlias, G.; Kostoglou, M.; Sotiropoulos, S.; Karapantsios, Th.

    2017-02-01

    Silver is the preservative used on the Russian segment of the International Space Station (ISS) to prevent microbial proliferation within potable water supplies. Yet, in the frame of the European Automated Transfer Vehicle (ATV) missions to ISS, silver depletion from water has been detected during ground transportation of this water to launch site, thereby indicating a degradation of water quality. This study investigates the silver loss from water when in contact with stainless steel surfaces. Experiments are conducted with several types of stainless steel surfaces being exposed to water containing 10 or 0.5 mg/L silver ions. Results show that silver deposits on stainless steel surfaces even when a passivation layer protects the metallic surface. The highest protection to silver deposition is offered by acid passivated and electropolished SS 316L. SEM and XPS experiments were carried out at several locations of the sample area that was in contact with the Ag solution and found similar morphological (SEM) and compositional (sputter-etch XPS) results. The results reveal that silver deposits uniformly across the wetted surface to a thickness larger than 3 nm. Moreover, evidence is provided that silver deposits in its metallic form on all stainless steel surfaces, in line with a galvanic deposition mechanism. Combination of ICP-MS and XPS results suggests a mechanism for Ag deposition/reduction with simultaneous substrate oxidation resulting in oxide growth at the exposed stainless steel surface.

  19. Relaxation of the silver/silver iodide electrode in aqueous solution

    NARCIS (Netherlands)

    Peverelli, K.J.

    1979-01-01

    The aim of this study is to detect and characterize relaxation processes on silver/silver iodide electrodes in aqueous electrolyte solution. The information obtained is to be used for an estimation of the consequences of similar processes on colloidal AgI

  20. The safety of nanocrystalline silver dressings on burns: a study of systemic silver absorption.

    Science.gov (United States)

    Vlachou, Evangelia; Chipp, Elizabeth; Shale, Elizabeth; Wilson, Yvonne T; Papini, Remo; Moiemen, Naiem S

    2007-12-01

    Wound dressings containing silver have been in widespread use for many years. However, there are few quantitative data on the systemic absorption of silver or whether there is associated clinical risk. To assess systemic silver levels when Acticoat dressings containing nanocrystalline silver were used, and to determine whether increases in such levels were associated with haematological or biochemical indicators of toxicity. A prospective, single-centre, open-label study of 30 patients with relatively small burns that required skin grafting. Serum silver levels were measured before, during and at discontinuation of the use of the Acticoat dressings, and again at 3 and 6 months following completion of treatment. The median total postoperative wound size was 12% of the total body surface area. The median time to maximum silver levels was 9 days. The median maximum serum silver level was 56.8 microg/l. The median serum level at 6 months was 0.8 microg/l. There were no haematological or biochemical indicators of toxicity associated with the silver absorption observed in this study. This study has confirmed our view that Acticoat products are safe for use on burns and they remain a standard part of treatment at our centre.

  1. Preparation of sintered silver nanosheets by coating technique using silver carbamate complex

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Hee-Yong; Cha, Jae-Ryung; Gong, Myoung-Seon, E-mail: msgong@dankook.ac.kr

    2015-03-01

    This study describes a coating technique approach for large-scale preparation of sintered silver nanosheets whose lateral dimensions were controlled in the thickness range of 50–65 nm. These procedures involved coating water-soluble poly (vinyl alcohol) (PVA) and silver 2-ethylhexylcarbamate (Ag-EHC), as well as thermal reduction of a silver precursor by heating at 150 °C, followed by dissolving away the PVA layer with alcoholic water. When the silver carbamate layer on the PVA layer was heated to 150 °C, the silver carbamate layer was thermally reduced and directed to grow into uniform sintered nanosheets with aspect ratios as high as 1000. The multi-stacked PVA/Ag structures and sintered silver nanosheets were confirmed by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. Measurements of the conductive property at room temperature indicated that these nanosheets were electrically continuous with a resistivity of approximately 7.3 × 10{sup −6} Ω cm. - Highlights: • A coating technique is used to make sintered Ag nanosheets. • PVA and silver carbamate act as a separation layer and a silver precursor. • The Ag nanosheets have thickness width 50–60 nm and width up to hundred μm. • The Ag nanosheets showed a resistivity of ca. 7.3 × 10{sup −6} Ω cm.

  2. Silver Recovery and Power Generation from Ammonia Chelated Silver Solution in a Bio-Electrochemical Reactor

    Science.gov (United States)

    Ho, N. A. D.; Babel, S.

    2017-06-01

    Silver has valuable features and limited availability, and thus recovery from wastewater or aqueous solutions plays an important role in environmental protection and economic profits. In this study, silver recovery along with power generation and COD removal were investigated in a bio-electrochemical system (BES). The BES comprised of an anode and a cathode chamber which were separated by a cation exchange membrane to prevent the cross-over of electrolytes. During the biological oxidation of acetate as an electron donor in the anode chamber, the reduction of ammonia chelated silver ions as electron acceptors in the cathode side occurred spontaneously. Results showed that a silver recovery of 99% and COD removal efficiency of 60% were achieved at the initial silver concentration of 1,000 mg/L after 48 hours of operation. The power generation improved 4.66%, from 3,618 to 3,795 mW/m3, by adding NaNO3 of 850 mg/L to the catholyte containing 2,000 mg/L of silver ions. Deposits on the cathode surface were characterized using scanning electron microscope (SEM) and energy dispersive X-ray (EDX). Metallic silver with dendritic structures and high purity were detected. This study demonstrated that BES technology can be employed to recover silver from complex chelating solution, produce electricity, and treat wastewater.

  3. In vitro percutaneous penetration and characterization of silver from silver-containing textiles

    NARCIS (Netherlands)

    Bianco, Carlotta; Kezic, Sanja; Crosera, Matteo; Svetličić, Vesna; Šegota, Suzana; Maina, Giovanni; Romano, Canzio; Larese, Francesca; Adami, Gianpiero

    2015-01-01

    The objective of this study was to determine the in vitro percutaneous penetration of silver and characterize the silver species released from textiles in different layers of full thickness human skin. For this purpose, two different wound dressings and a garment soaked in artificial sweat were

  4. Protection of neurons derived from human neural progenitor cells by veratridine.

    Science.gov (United States)

    Morgan, Peter J; Ortinau, Stefanie; Frahm, Jana; Krüger, Norman; Rolfs, Arndt; Frech, Moritz J

    2009-08-26

    The survival of developing dopaminergic neurons has been shown to be modulated by voltage-dependent mechanisms. Manipulation of these mechanisms in human neural progenitor cell cultures could improve the survival of immature dopaminergic neurons, and therefore aid research into pharmacological and cell replacement therapies for Parkinson's disease. Here, we examined the effect of the Na+ channel agonist veratridine on the human fetal neural progenitor ReNcell VM cell line. Neuronal differentiation was determined by immunocytochemistry, whereas patch clamp recordings showed the expression of functional voltage-gated sodium channels. Our results show that veratridine is neuroprotective in human fetal neural progenitor cells, which may benefit studies investigating neuronal development by reducing premature death amongst developing neurons.

  5. Novel Nanohybrids of Silver Particles on Clay Platelets for Inhibiting Silver-Resistant Bacteria

    Science.gov (United States)

    Su, Hong-Lin; Lin, Siou-Hong; Wei, Jiun-Chiou; Pao, I-Chuan; Chiao, Shu-Her; Huang, Chieh-Chen; Lin, Shinn-Zong; Lin, Jiang-Jen

    2011-01-01

    We develop a novel nanohybrid showing a strong antibacterial activity on all of the tested pathogens, including methicillin-resistant Staphylococcus auerus and silver-resistant E. coli. The nanohybrid consists of silver nanoparticles (AgNPs) supported on 1 nm-thick silicate platelets (NSPs). The AgNP/NSP nanohybrid enables to encapsulate bacteria and triggers death signals from the cell membrane. The geographic shape of the NSPs concentrates AgNPs but impedes their penetration into attached cells, mitigating the detrimental effect of silver ion deposition in applied tissues. Moreover, the tightly tethered AgNPs on NSP surface achieve a stronger biocidal effect than silver nitrate, but bypassing Ag+ mechanism, on silver-resistant bacteria. This nanohybrid presents an effective and safe antimicrobial agent in a new perspective. PMID:21695045

  6. Novel nanohybrids of silver particles on clay platelets for inhibiting silver-resistant bacteria.

    Directory of Open Access Journals (Sweden)

    Hong-Lin Su

    Full Text Available We develop a novel nanohybrid showing a strong antibacterial activity on all of the tested pathogens, including methicillin-resistant Staphylococcus auerus and silver-resistant E. coli. The nanohybrid consists of silver nanoparticles (AgNPs supported on 1 nm-thick silicate platelets (NSPs. The AgNP/NSP nanohybrid enables to encapsulate bacteria and triggers death signals from the cell membrane. The geographic shape of the NSPs concentrates AgNPs but impedes their penetration into attached cells, mitigating the detrimental effect of silver ion deposition in applied tissues. Moreover, the tightly tethered AgNPs on NSP surface achieve a stronger biocidal effect than silver nitrate, but bypassing Ag(+ mechanism, on silver-resistant bacteria. This nanohybrid presents an effective and safe antimicrobial agent in a new perspective.

  7. Lumping Izhikevich neurons

    NARCIS (Netherlands)

    Visser, S.; van Gils, Stephanus A.

    2014-01-01

    We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behaviour intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting

  8. Silver nanoparticles from silver halide photography to plasmonics

    CERN Document Server

    Tani, Tadaaki

    2015-01-01

    This book provides systematic knowledge and ideas on nanoparticles of Ag and related materials. While Ag and metal nanoparticles are essential for plasmonics, silver halide (AgX) photography relies to a great extent on nanoparticles of Ag and AgX which have the same crystal structure and have been studied extensively for many years. This book has been written to combine the knowledge of nanoparticles of Ag and related materials in plasmonics and AgX photography in order to provide new ideas for metal nanoparticles in plasmonics. Chapters 1–3 of this book describe the structure and formation of nanoparticles of Ag and related materials. Systematic descriptions of the structure and preparation of Ag, Au, and noble-metal nanoparticles for plasmonics are followed by and related to those of nanoparticles of Ag and AgX in AgX photography. Knowledge of the structure and preparation of Ag and AgX nanoparticles in photography covers nanoparticles with widely varying sizes, shapes, and structures, and formation proce...

  9. Glass frits coated with silver nanoparticles for silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yingfen, E-mail: lyf350857423@163.com; Gan, Weiping; Zhou, Jian; Li, Biyuan

    2015-06-30

    Graphical abstract: - Highlights: • Silver-coated glass frits for solar cells were prepared by electroless plating. • Gum Arabic was used as the activating agent of glass frits. • Silver-coated glass frits can improve the photovoltaic performances of solar cells. - Abstract: Glass frits coated with silver nanoparticles were prepared by electroless plating. Gum Arabic (GA) was used as the activating agent of glass frits without the assistance of stannous chloride or palladium chloride. The silver-coated glass frits prepared with different GA dosages were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA). The characterization results indicated that silver-coated glass frits had the structures of both glass and silver. Spherical silver nanoparticles were distributed on the glass frits evenly. The density and particle size of silver nanoparticles on the glass frits can be controlled by adjusting the GA dosage. The silver-coated glass frits were applied to silver pastes to act as both the densification promoter and silver crystallite formation aid in the silver electrodes. The prepared silver-coated glass frits can improve the photovoltaic performances of solar cells.

  10. Spiking neuron network Helmholtz machine

    National Research Council Canada - National Science Library

    Sountsov, Pavel; Miller, Paul

    2015-01-01

    .... This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational...

  11. Identifying neuronal oscillations using rhythmicity

    NARCIS (Netherlands)

    Fransen, A.M.M.; Ede, F.L. van; Maris, E.G.G.

    2015-01-01

    Neuronal oscillations are a characteristic feature of neuronal activity and are typically investigated through measures of power and coherence. However, neither of these measures directly reflects the distinctive feature of oscillations: their rhythmicity. Rhythmicity is the extent to which future

  12. Silver, gold, and alloyed silver-gold nanoparticles: characterization and comparative cell-biologic action

    Energy Technology Data Exchange (ETDEWEB)

    Mahl, Dirk; Diendorf, Joerg; Ristig, Simon [University of Duisburg-Essen, Department of Inorganic Chemistry, Center for Nanointegration Duisburg-Essen (CeNIDE) (Germany); Greulich, Christina [Ruhr-University of Bochum, Bergmannsheil University Hospital/Surgical Research (Germany); Li Zian; Farle, Michael [University of Duisburg-Essen, Faculty of Physics, Center for Nanointegration Duisburg-Essen (CeNIDE) (Germany); Koeller, Manfred [Ruhr-University of Bochum, Bergmannsheil University Hospital/Surgical Research (Germany); Epple, Matthias, E-mail: matthias.epple@uni-due.de [University of Duisburg-Essen, Department of Inorganic Chemistry, Center for Nanointegration Duisburg-Essen (CeNIDE) (Germany)

    2012-10-15

    Silver, gold, and silver-gold-alloy nanoparticles were prepared by citrate reduction modified by the addition of tannin during the synthesis, leading to a reduction in particle size by a factor of three. Nanoparticles can be prepared by this easy water-based synthesis and subsequently functionalized by the addition of either tris(3-sulfonatophenyl)phosphine or poly(N-vinylpyrrolidone). The resulting nanoparticles of silver (diameter 15-25 nm), gold (5-6 nm), and silver-gold (50:50; 10-12 nm) were easily dispersable in water and also in cell culture media (RPMI + 10 % fetal calf serum), as shown by nanoparticle tracking analysis and differential centrifugal sedimentation. High-resolution transmission electron microscopy showed a polycrystalline nature of all nanoparticles. EDX on single silver-gold nanoparticles indicated that the concentration of gold is higher inside a nanoparticle. The biologic action of the nanoparticles toward human mesenchymal stem cells (hMSC) was different: Silver nanoparticles showed a significant concentration-dependent influence on the viability of hMSC. Gold nanoparticles showed only a small effect on the viability of hMSC after 7 days. Surprisingly, silver-gold nanoparticles had no significant influence on the viability of hMSC despite the silver content. Silver nanoparticles and silver-gold nanoparticles in the concentration range of 5-20 {mu}g mL{sup -1} induced the activation of hMSC as indicated by the release of IL-8. In contrast, gold nanoparticles led to a reduction of the release of IL-6 and IL-8.

  13. Synthesis and characterization of silver nanoparticles from (bis)alkylamine silver carboxylate precursors

    Science.gov (United States)

    Uznanski, Pawel; Zakrzewska, Joanna; Favier, Frederic; Kazmierski, Slawomir; Bryszewska, Ewa

    2017-03-01

    A comparative study of amine and silver carboxylate adducts [R1COOAg-2(R2NH2)] (R1 = 1, 7, 11; R2 = 8, 12) as a key intermediate in NPs synthesis is carried out via differential scanning calorimetry, solid-state FT-infrared spectroscopy, 13C CP MAS NMR, powder X-ray diffraction and X-ray photoelectron spectroscopy, and various solution NMR spectroscopies (1H and 13C NMR, pulsed field gradient spin-echo NMR, and ROESY). It is proposed that carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination as opposed to bridging bidentate coordination of pure silver carboxylates resulting from the formation of dimeric units. All complexes are packed as lamellar bilayer structures. Silver carboxylate/amine complexes show one first-order melting transition. The evidence presented in this study shows that phase behavior of monovalent metal carboxylates are controlled, mainly, by head group bonding. In solution, insoluble silver salt is stabilized by amine molecules which exist in dynamic equilibrium. Using (bis)amine-silver carboxylate complex as precursor, silver nanoparticles were fabricated. During high-temperature thermolysis, the (bis)amine-carboxylate adduct decomposes to produce silver nanoparticles of small size. NPs are stabilized by strongly interacting carboxylate and trace amounts of amine derived from the silver precursor interacting with carboxylic acid. A corresponding aliphatic amide obtained from silver precursor at high-temperature reaction conditions is not taking part in the stabilization. Combining NMR techniques with FTIR, it was possible to follow an original stabilization mechanism.

  14. Synthesis and characterization of silver nanoparticles from (bis)alkylamine silver carboxylate precursors

    Energy Technology Data Exchange (ETDEWEB)

    Uznanski, Pawel, E-mail: puznansk@cbmm.lodz.pl; Zakrzewska, Joanna [Centre of Molecular and Macromolecular Studies, PAS (Poland); Favier, Frederic, E-mail: fredf@univ-montp2.fr [Université Montpellier II, ICGM - UMR5253- Equipe AIME (France); Kazmierski, Slawomir; Bryszewska, Ewa [Centre of Molecular and Macromolecular Studies, PAS (Poland)

    2017-03-15

    A comparative study of amine and silver carboxylate adducts [R{sub 1}COOAg-2(R{sub 2}NH{sub 2})] (R{sub 1} = 1, 7, 11; R{sub 2} = 8, 12) as a key intermediate in NPs synthesis is carried out via differential scanning calorimetry, solid-state FT-infrared spectroscopy, {sup 13}C CP MAS NMR, powder X-ray diffraction and X-ray photoelectron spectroscopy, and various solution NMR spectroscopies ({sup 1}H and {sup 13}C NMR, pulsed field gradient spin-echo NMR, and ROESY). It is proposed that carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination as opposed to bridging bidentate coordination of pure silver carboxylates resulting from the formation of dimeric units. All complexes are packed as lamellar bilayer structures. Silver carboxylate/amine complexes show one first-order melting transition. The evidence presented in this study shows that phase behavior of monovalent metal carboxylates are controlled, mainly, by head group bonding. In solution, insoluble silver salt is stabilized by amine molecules which exist in dynamic equilibrium. Using (bis)amine-silver carboxylate complex as precursor, silver nanoparticles were fabricated. During high-temperature thermolysis, the (bis)amine-carboxylate adduct decomposes to produce silver nanoparticles of small size. NPs are stabilized by strongly interacting carboxylate and trace amounts of amine derived from the silver precursor interacting with carboxylic acid. A corresponding aliphatic amide obtained from silver precursor at high-temperature reaction conditions is not taking part in the stabilization. Combining NMR techniques with FTIR, it was possible to follow an original stabilization mechanism.

  15. Polypyrrole-silver Nanocomposite: Synthesis and Characterization

    Directory of Open Access Journals (Sweden)

    D. M. Nerkar

    2016-07-01

    Full Text Available Polypyrrole-Silver (PPy-Ag nanocomposite has been successfully synthesized by the chemical oxidative polymerization of pyrrole with iron (III chloride as an oxidant, in the presence of a colloidal suspension of silver nanoparticles. Turkevich method (Citrate reduction method was used for the synthesis of silver nanoparticles (Ag NPs. The silver nanoparticles were characterized by UV-Visible spectroscopy which showed an absorption band at 423 nm confirming the formation of nanoparticles. PPy-Ag nanocomposite was characterized by Transmission Electron Microscopy (TEM, Scanning Electron Microscopy (SEM, Fourier Transform Infrared Spectroscopy (FTIR and X-ray diffraction (XRD techniques for morphological and structural confirmations. TEM and SEM images revealed that the silver nanoparticles were well dispersed in the PPy matrix. XRD pattern showed that PPy is amorphous but the presence of the peaks at 2q values of 38.24°, 44.57°, 64.51° and 78.45° corresponding to a cubic phase of silver, revealed the incorporation of silver nanoparticles in the PPy matrix. A possible formation mechanism of PPy-Ag nanocomposite was also proposed. The electrical conductivity of PPy-Ag nanocomposite was studied using two probe method. The electrical conductivity of the PPy-Ag nanocomposite prepared was found to be 4.657´10- 2 S/cm, whereas that of pure PPy was found to be 9.85´10-3 S/cm at room temperature (303 K. The value of activation energy (Ea for pure PPy was 0.045 eV while it decreased to 0.034 eV for PPy-Ag nanocomposite. The synthesized nanocomposite powder can be utilized as a potential material for fabrication of gas sensors operating at room temperature.

  16. Spatial-specific functions in retrograde neuronal signalling.

    Science.gov (United States)

    Zahavi, Eitan Erez; Maimon, Roy; Perlson, Eran

    2017-07-01

    Neurons are highly polarized cells, possessing long axons that can extend to more than 1-m long in adult humans. In order to survive and maintain proper functions, neurons have to respond accurately in both space and time to intracellular or intercellular cues. The regulation of these comprehensive responses involves ligand-receptor interactions, trafficking and local protein synthesis. Alterations in these mechanisms can lead to cellular dysfunction and disease. Although studies on the transport and localization of signalling endosomes along the axon have shed light on some central pathways of neuronal survival and growth as well as synapse function, little is known about the spatiotemporal mechanisms that allow the same molecule to signal differently at diverse subcellular locations and in specific neuronal populations. In this review, we will provide an overview of retrograde axonal signalling mechanisms and discuss new advances in our understanding of the spatial-specific regulation of neuronal signalling and functions, mechanisms that allow the same signal to have a different effect in another subcellular location. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways.

    Science.gov (United States)

    Kim, Jisung; Lee, Siyoung; Choi, Bo-Ryoung; Yang, Hee; Hwang, Youjin; Park, Jung Han Yoon; LaFerla, Frank M; Han, Jung-Soo; Lee, Ki Won; Kim, Jiyoung

    2017-02-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane. Sulforaphane enhanced neuronal BDNF expression and increased levels of neuronal and synaptic molecules such as MAP2, synaptophysin, and PSD-95 in primary cortical neurons and 3 × Tg-AD mice. Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice. Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons. Chromatin immunoprecipitation analysis revealed that sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition. These findings suggest that sulforaphane has the potential to prevent neuronal disorders such as Alzheimer's disease by epigenetically enhancing neuronal BDNF expression and its TrkB signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. The effects of food availability on growth and reproduction of Daphnia magna exposed to silver nanoparticles

    DEFF Research Database (Denmark)

    Mackevica, Aiga; Skjolding, Lars Michael; Gergs, A.

    offspring, and number of neonates produced. The data obtained from the chronic tests are intended for modeling using the Dynamic Energy Budget (DEB) theory, which will hopefully provide information on growth and reproduction strategy of the test animals. The concentrations of silver in the test medium over...... to controls, whereas concentrations above 10 μgAg/L resulted in inhibition of growth and reproduction as well as an increased mortality. The addition of higher amounts of food showed a beneficial effect on animal survival, growth and reproduction. Similar as in normal food availability treatment, animals......The number of available studies on the acute effects of silver nanoparticles (AgNP) on aquatic organisms has increased dramatically in recent years, but there is still very limited information available on chronic effects. In this study, a series of Daphnia magna 21-days reproduction test (OECD 211...

  19. Motor neuron disease in blacks

    African Journals Online (AJOL)

    1989-08-19

    Aug 19, 1989 ... We reported earlier that motor neuron disease occurs more commonly among blacks than Parkinson's disease, which is relatively rare in this race group.! The hypothesis that these conditions, and other neuronal abiotrophies, are the result of previous subclinical neuronal insult and subsequent age-related.

  20. Simple model of spiking neurons.

    Science.gov (United States)

    Izhikevich, E M

    2003-01-01

    A model is presented that reproduces spiking and bursting behavior of known types of cortical neurons. The model combines the biologically plausibility of Hodgkin-Huxley-type dynamics and the computational efficiency of integrate-and-fire neurons. Using this model, one can simulate tens of thousands of spiking cortical neurons in real time (1 ms resolution) using a desktop PC.

  1. Moving Neurons back into place

    OpenAIRE

    Kerjan, Geraldine; Gleeson, Joseph G.

    2009-01-01

    Subcortical band heterotopia (SBH) is a neuron migration disorder characterized by an aberrant ‘band-like’ accumulation of neurons within the neocortical white matter, frequently leading to mental retardation and epilepsy. SBH can now be regressed by reactivating neuronal migration.

  2. Neuronal substrate of eating disorders

    OpenAIRE

    Timofeeva, Elena; Calvez, Juliane

    2014-01-01

    Eating disorders are devastating and life-threatening psychiatric diseases. Although clinical and experimental investigations have significantly progressed in discovering the neuronal causes of eating disorders, the exact neuronal and molecular mechanisms of the development and maintenance of these pathologies are not fully understood. The complexity of the neuronal substrate of eating disorders hampers progress in revealing the precise mechanisms. The present re...

  3. Understanding Neuronal Mechanisms of Epilepsy ...

    Indian Academy of Sciences (India)

    Admin

    Control il ti. Human brain. Control epileptic. Mutani et al., 1994 ... of Calcium Transients Evoked in. Response to Spontaneous Epileptic ... Proof : Feed forward inhibition in subiculum. CA1. Subiculum. Stimulation artifact. -60 mV. Excitatory neuron. Inhibitory neuron. Excitatory neuron. Excitatory. Synapse. Inhibitory. Synapse.

  4. Effect of size of unfed fry at release on survival and growth of juvenile steelhead in streams and a hatchery (Study sites: Dworshak Hatchery, Silver Creek, and Twenty-Mile Creek; Stock: Dworshak hatchery; Year classes: 1996 and 1999): Chapter 7

    Science.gov (United States)

    Rubin, Stephen P.; Reisenbichler, Reginald R.; Wetzel, Lisa A.; Stenberg, Karl D.

    2012-01-01

    We tested whether differences in size of unfed fry at release affected survival and growth of juvenile steelhead Oncorhynchus mykiss in hatchery ponds and streams. Differences in fry size were produced by selecting and spawning females that differed in the mean size of their eggs. Experiments were initiated in 1996 and 1999 with hatchery steelhead returning to the Clearwater River, Idaho. Fry size groups were small (mean fork length=26.7 mm, mean weight=0.149 g) and large (28.1 mm, 0.197 g) in 1996 and small (27.5 mm, 0.159 g), medium (28.2 mm, 0.190 g), and large (28.9 mm, 0.201 g) in 1999. Survival in the hatchery to near the end of the standard one year rearing period and in streams to late summer, three months after release, was higher for the large than for the small group in 1996 but was similar among groups in 1999. Survival in streams to age - 1 appeared to show the same pattern (large>small in 1996; no difference in 1999), but differences among fry size groups in emigration as well as mortality may have been involved. The inconsistency between years may have resulted because some 1996 female parents of the small group had exceptionally small eggs and were a year younger than the other 1996 females and all 1999 females. Growth in the hatchery was similar among groups in both years whereas growth in streams was faster for the large than for the small group in both years and intermediate for the medium group in 1999. Growth in streams appeared to be limited by food availability. Initially large fry probably out - competed smaller fry for limited food; however, we found no evidence that dispersal from release sites or emigration from streams was caused by competitive displacement of small by larger fish. 

  5. Silver nitrate masquerading as a radiopaque foreign body.

    Science.gov (United States)

    Healy, Claragh; Canney, Mark; Murphy, Adrian; Regan, Padraic

    2007-04-01

    Silver nitrate is commonly used as a method of chemical cauterization to areas of hypergranulation. We report two cases wherein silver nitrate in the hand was misinterpreted radiologically as foreign bodies.

  6. Electrical properties of silver selenide thin films prepared by reactive ...

    Indian Academy of Sciences (India)

    Unknown

    2001-07-29

    805 Å. Keywords. Thin film; silver selenide; reactive evaporation; electrical conductivity. 1. Introduction. Silver selenide attracts the interest of researchers because of its application in the switching devices. The binary and ternary ...

  7. Green biosynthesis of silver nanoparticles using Curcuma longa tuber powder

    National Research Council Canada - National Science Library

    Shameli, Kamyar; Ahmad, Mansor Bin; Zamanian, Ali; Sangpour, Parvanh; Shabanzadeh, Parvaneh; Abdollahi, Yadollah; Zargar, Mohsen

    2012-01-01

    .... In this study, silver nanoparticles were biosynthesized from aqueous silver nitrate through a simple and eco-friendly route using Curcuma longa tuber-powder extracts, which acted as a reductant...

  8. DNA-Mediated Morphological Control of Silver Nanoparticles.

    Science.gov (United States)

    Li, Jiuxing; Zhu, Zhi; Liu, Fang; Zhu, Bingqing; Ma, Yanli; Yan, Jinmao; Lin, Bingqian; Ke, Guoliang; Liu, Rudi; Zhou, Leiji; Tu, Song; Yang, Chaoyong

    2016-10-01

    It is demonstrated that DNA can be used to control the synthesis of silver nanoplates with different morphologies using spherical silver seeds. UV-vis spectroscopy, transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy are used to characterize the synthesized nanoparticles. Silver nanoprisms are encoded by poly C and poly G, while silver flower bouquets and silver nanodiscs are synthesized using poly A and poly T, respectively. The length of DNA is found to have little effect on the morphology of silver nanoparticles. Moreover, the synthesized silver nanoplates are found to have high surface enhanced Raman scattering enhancement ability, good antibacterial activity, and good biocompatibility. These discoveries will broaden the application of DNA in nanoscience and will provide a new platform to investigate the interaction between DNA sequences and silver nanoparticles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Silver-catalyzed synthesis of amides from amines and aldehydes

    Science.gov (United States)

    Madix, Robert J; Zhou, Ling; Xu, Bingjun; Friend, Cynthia M; Freyschlag, Cassandra G

    2014-11-18

    The invention provides a method for producing amides via the reaction of aldehydes and amines with oxygen adsorbed on a metallic silver or silver alloy catalyst. An exemplary reaction is shown in Scheme 1: (I), (II), (III). ##STR00001##

  10. Functional finishing of cotton fabrics using silver nanoparticles.

    Science.gov (United States)

    Vigneshwaran, N; Kathe, A A; Varadarajan, P V; Nachane, R P; Balasubramanya, R H

    2007-06-01

    We have reported a novel in situ synthesis protocol for silver nanoparticles onto cotton fabrics. Here, cotton fabric immersed in silver nitrate solution is autoclaved at 15 psi, 121 degrees C for 15 min. At this temperature and pressure, the aldehyde terminal of starch (residual size material on cotton fabric) reduced the silver nitrate to silver metal and simultaneously stabilized the nanoparticles on fabric itself. The UV-visible absorption spectrum of both cotton fabrics and bath solution showed a typical absorption peak at 420 nm corresponding to the surface plasmon resonance of silver nanoparticles. With the help of transmission electron micrographs, the average size of the dislodged silver nanoparticles in water is calculated to be 20.9 +/- 13.7 nm. This silver nanoparticles impregnated cotton fabrics showed excellent antibacterial activity against Staphylococcus aureus and bacteriostasis activity against Klebsiella pneumoniae. Also, silver nanoparticles impregnated fabrics expressed significant UV-protection capability in comparison with the untreated fabrics.

  11. Sintered silver joints via controlled topography of electronic packaging subcomponents

    Science.gov (United States)

    Wereszczak, Andrew A.

    2014-09-02

    Disclosed are sintered silver bonded electronic package subcomponents and methods for making the same. Embodiments of the sintered silver bonded EPSs include topography modification of one or more metal surfaces of semiconductor devices bonded together by the sintered silver joint. The sintered silver bonded EPSs include a first semiconductor device having a first metal surface, the first metal surface having a modified topography that has been chemically etched, grit blasted, uniaxial ground and/or grid sliced connected to a second semiconductor device which may also include a first metal surface with a modified topography, a silver plating layer on the first metal surface of the first semiconductor device and a silver plating layer on the first metal surface of the second semiconductor device and a sintered silver joint between the silver plating layers of the first and second semiconductor devices which bonds the first semiconductor device to the second semiconductor device.

  12. Ink composition for making a conductive silver structure

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Steven B.; Lewis, Jennifer A.

    2016-10-18

    An ink composition for making a conductive silver structure comprises a silver salt and a complex of (a) a complexing agent and a short chain carboxylic acid or (b) a complexing agent and a salt of a short chain carboxylic acid, according to one embodiment. A method for making a silver structure entails combining a silver salt and a complexing agent, and then adding a short chain carboxylic acid or a salt of the short chain carboxylic acid to the combined silver salt and a complexing agent to form an ink composition. A concentration of the complexing agent in the ink composition is reduced to form a concentrated formulation, and the silver salt is reduced to form a conductive silver structure, where the concentrated formulation and the conductive silver structure are formed at a temperature of about 120.degree. C. or less.

  13. Biosynthesis of silver nanoparticles by Aspergillus niger , Fusarium ...

    African Journals Online (AJOL)

    ... scanning electron microscope (SEM). Results indicate the synthesis of silver nanoparticles in the reaction mixture. The synthesis of nanoparticles would be suitable for developing a microbial nanotechnology biosynthesis process for mass scale production. Keywords: Silver nanoparticles, biosynthesis, fungi, Aspergillus.

  14. In vivo comparisons of silver nanoparticle and silver ion transport after intranasal delivery in mice.

    Science.gov (United States)

    Falconer, Jonathan L; Grainger, David W

    2017-10-20

    Silver nanoparticles (AgNPs) are widely available as consumer goods, and over-the-counter or nutraceutical products used for alleged therapeutic and antibacterial properties. Among these products, AgNP topical therapy is proposed for treating patients with upper airway bacterial rhinosinusitis. While silver ion release from AgNPs in biological systems is well known, limited investigations actually characterize this silver ion release and their subsequent biological effects distinct from delivered particulate metallic silver. This is in part due to the analytical complexity and difficulty involved in distinguishing silver ion release from metallic AgNPs in biological media. Therefore, this study compared intranasal administration of AgNPs versus soluble silver ion (AgNO3) control to examine their transport and biological differences in tissues. First, we compared bactericidal activities of AgNPs and AgNO3 in those bacteria commonly associated with clinical rhinosinusitis in vitro. Next, we evaluated silver residence time in the sinus cavity after intranasal delivery of AgNPs and AgNO3 to mice, and characterized tissue distribution of silver in the sinonasal mucosal epithelium. We found that AgNPs show reduced bactericidal activity compared to AgNO3 (i.e., MBC of 15ppm compared to 5ppm), and significantly lower residence times in the sinus cavity (AgNP concentrations of 3.76ppm after 3h compared to 9ppm for AgNO3). AgNPs were not readily taken up into or through respiratory epithelium, with very low silver levels found in blood and no detectable silver measured in the olfactory bulb and brain. Results indicate that limited tissue distribution of silver detected from AgNPs is due to AgNP dissolution to silver ion. AgNPs therefore demonstrate adequate safety through limited penetration and absorption, but limited potential therapeutic efficacy as antimicrobials in nasal applications, as concentrations of silver in the sinus cavity drop below the minimum bactericidal

  15. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence.

    Science.gov (United States)

    Fries, Pascal

    2005-10-01

    At any one moment, many neuronal groups in our brain are active. Microelectrode recordings have characterized the activation of single neurons and fMRI has unveiled brain-wide activation patterns. Now it is time to understand how the many active neuronal groups interact with each other and how their communication is flexibly modulated to bring about our cognitive dynamics. I hypothesize that neuronal communication is mechanistically subserved by neuronal coherence. Activated neuronal groups oscillate and thereby undergo rhythmic excitability fluctuations that produce temporal windows for communication. Only coherently oscillating neuronal groups can interact effectively, because their communication windows for input and for output are open at the same times. Thus, a flexible pattern of coherence defines a flexible communication structure, which subserves our cognitive flexibility.

  16. Silver Nanoparticles and Mitochondrial Interaction

    Directory of Open Access Journals (Sweden)

    Eriberto Bressan

    2013-01-01

    Full Text Available Nanotechnology has gone through a period of rapid growth, thus leading to the constant increase in the application of engineered nanomaterials in daily life. Several different types of nanoparticles have been engineered to be employed in a wide array of applications due to their high surface to volume ratio that leads to unique physical and chemical properties. So far, silver nanoparticles (AgNps have been used in many more different medical devices than any other nanomaterial, mainly due to their antimicrobial properties. Despite the promising advantages posed by using AgNps in medical applications, the possible health effects associated with the inevitable human exposure to AgNps have raised concerns as to their use since a clear understanding of their specific interaction with biological systems has not been attained yet. In light of such consideration, aim of the present work is the morphological analysis of the intracellular behavior of AgNps with a diameter of 10 nm, with a special attention to their interaction with mitochondria.

  17. Visual Experience Facilitates BDNF-Dependent Adaptive Recruitment of New Neurons in the Postembryonic Optic Tectum.

    Science.gov (United States)

    Hall, Zachary J; Tropepe, Vincent

    2018-02-21

    Postembryonic brain development is sensitive to environmental input and sensory experience, but the mechanisms underlying healthy adaptive brain growth are poorly understood. Here, we tested the importance of visual experience on larval zebrafish ( Danio rerio ) postembryonic development of the optic tectum (OT), a midbrain structure involved in visually guided behavior. We first characterized postembryonic neurogenic growth in OT, in which new neurons are generated along the caudal tectal surface and contribute appositionally to anatomical growth. Restricting visual experience during development by rearing larvae in dim light impaired OT anatomical and neurogenic growth, specifically by reducing the survival of new neurons in the medial periventricular gray zone. Neuronal survival in the OT was reduced only when visual experience was restricted for the first 5 d following new neuron generation, suggesting that tectal neurons exhibit an early sensitive period in which visual experience protects these cells from subsequent neuronal loss. The effect of dim rearing on neuronal survival was mimicked by treatment with an NMDA receptor antagonist early, but not later, in a new neuron's life. Both dim rearing and antagonist treatment reduced BDNF production in the OT, and supplementing larvae with exogenous BDNF during dim rearing prevented neuronal loss, suggesting that visual experience protects new tectal neurons through neural activity-dependent BDNF expression. Collectively, we present evidence for a sensitive period of neurogenic adaptive growth in the larval zebrafish OT that relies on visual experience-dependent mechanisms. SIGNIFICANCE STATEMENT Early brain development is shaped by environmental factors via sensory input; however, this form of experience-dependent neuroplasticity is traditionally studied as structural and functional changes within preexisting neurons. Here, we found that restricting visual experience affects development of the larval zebrafish

  18. Sleep disordered breathing in motor neurone disease.

    Science.gov (United States)

    D'Cruz, Rebecca F; Murphy, Patrick B; Kaltsakas, Georgios

    2018-01-01

    Motor neurone disease (MND) is a neurodegenerative disease defined by axonal loss and gliosis of upper and lower motor neurones in the motor cortex, lower brainstem nuclei and ventral horn of the spinal cord. MND is currently incurable and has a poor prognosis, with death typically occurring 3 to 5 years after disease onset. The disease is characterised by rapidly progressive weakness leading to paralysis, fasciculations, bulbar symptoms (including dysarthria and dysphagia) and respiratory compromise. Respiratory complications arise as a result of weakness of upper airway (pharyngeal and laryngeal) muscles and respiratory muscles (diaphragm, intercostal and accessory muscles) leading to respiratory failure. Due to early involvement of respiratory muscles in MND, sleep disordered breathing (SDB) occurs at a higher frequency than compared to the general population. SDB usually precedes daytime respiratory symptoms and chronic respiratory failure. It significantly impacts upon patients' quality of life and survival and its presence may predict prognosis. Managing SDB in MND with non-invasive ventilation (NIV) improves quality of life and survival. Early identification and management of SDB in MND patients is therefore crucial. This update will review assessments of respiratory muscle function, types of SDB and the effects of NIV in patients with MND.

  19. Multifunctionality of silver closo-boranes

    Science.gov (United States)

    Paskevicius, Mark; Hansen, Bjarne R. S.; Jørgensen, Mathias; Richter, Bo; Jensen, Torben R.

    2017-04-01

    Silver compounds share a rich history in technical applications including photography, catalysis, photocatalysis, cloud seeding and as antimicrobial agents. Here we present a class of silver compounds (Ag2B10H10 and Ag2B12H12) that are semiconductors with a bandgap at 2.3 eV in the green visible light spectrum. The silver boranes have extremely high ion conductivity and dynamic-anion facilitated Ag+ migration is suggested based on the structural model. The ion conductivity is enhanced more than two orders of magnitude at room temperature (up to 3.2 mS cm-1) by substitution with AgI to form new compounds. Furthermore, the closo-boranes show extremely fast silver nano-filament growth when excited by electrons during transmission electron microscope investigations. Ag nano-filaments can also be reabsorbed back into Ag2B12H12. These interesting properties demonstrate the multifunctionality of silver closo-boranes and open up avenues in a wide range of fields including photocatalysis, solid state ionics and nano-wire production.

  20. Characterization of antibacterial silver coated yarns.

    Science.gov (United States)

    Pollini, M; Russo, M; Licciulli, A; Sannino, A; Maffezzoli, A

    2009-11-01

    Surface treatments of textile fibers and fabrics significantly increase their performances for specific biomedical applications. Nowadays, silver is the most used antibacterial agent with a number of advantages. Among them, it is worth to note the high degree of biocompatibility, an excellent resistance to sterilization conditions, antibacterial properties with respect to different bacteria associated with a long-term of antibacterial efficiency. However, there are only a few antibacterial fibres available, mainly synthetic with high production cost and limited effectiveness. Cotton yarns with antimicrobial properties are most suitable for wound healing applications and other medical treatments thanks to their excellent moisture absorbance while synthetic based fibres are most suitable for industrial applications such as automotive tapestry and air filters. The silver-coated fibers were developed applying an innovative and low cost silver deposition technique for natural and synthetic fibers or yarns. The structure and morphology of the silver nanoclusters on the fibers was observed by scanning electron microscopy (SEM), atomic force microscopy analysis (AFM) and XRD analysis, and quantitatively confirmed by thermogravimetric analysis (TGA) measurements. Good silver coating stability has been confirmed performing several industrial washing. Antimicrobial tests with Escherichia coli were performed.

  1. Complex conductivity response to silver nanoparticles in ...

    Science.gov (United States)

    The increase in the use of nanoscale materials in consumer products has resulted in a growing concern of their potential hazard to ecosystems and public health from their accidental or intentional introduction to the environment. Key environmental, health, and safety research needs include knowledge and methods for their detection, characterization, fate, and transport. Specifically, techniques available for the direct detection and quantification of their fate and transport in the environment are limited. Their small size, high surface area to volume ratio, interfacial, and electrical properties make metallic nanoparticles, such as silver nanoparticles, good targets for detection using electrical geophysical techniques. Here we measured the complex conductivity response to silver nanoparticles in sand columns under varying moisture conditions (0–30%), nanoparticle concentrations (0–10 mg/g), lithology (presence of clay), pore water salinity (0.0275 and 0.1000 S/m), and particle size (35, 90–210 and 1500–2500 nm). Based on the Cole-Cole relaxation models we obtained the chargeability and the time constant. We demonstrate that complex conductivity can detect silver nanoparticles in porous media with the response enhanced by higher concentrations of silver nanoparticles, moisture content, ionic strength, clay content and particle diameter. Quantification of the volumetric silver nanoparticles content in the porous media can also be obtained from complex co

  2. Biosynthesis of PVA encapsulated silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Sharmila Chandran

    2016-10-01

    Full Text Available Green synthesis of metal nanoparticles is an important technique in the methods of eco-friendly nanoparticle production. The synthesis of silver nanoparticles was accomplished using Ocimum sanctum leaf extract at room temperature. These particles were then encapsulated with polyvinyl alcohol (PVA polymer matrix. The presence of silver was confirmed by different characterization techniques such as UV–vis spectroscopy, Fourier transform infrared spectroscopy (FTIR and X-Ray Diffraction (XRD. Scanning electron microscopic (SEM images of the synthesized powder shows spherical shaped silver nanoparticles embedded in sponge-like polymer matrix. The energy dispersive X-ray analysis confirms the presence of elemental silver along with iron signal. Energy dispersive signal corresponding to elemental iron has been attributed to O. sanctum plant. The silver nanoparticles in PVA matrix thus obtained shows high antibacterial activity against gram positive Staphylococcus aureus (S. aureus and gram negative Escherichia coli (E. coli water borne bacteria. The inhibition zone against S. aureus and E. coli were also calculated.

  3. Vascular and neuronal ischemic damage in cryonics patients.

    Science.gov (United States)

    Best, Benjamin P

    2012-04-01

    Cryonics technology seeks to cryopreserve the anatomical basis of the mind so that future medicine can restore legally dead cryonics patients to life, youth, and health. Most cryonics patients experience varying degrees of ischemia and reperfusion injury. Neurons can survive ischemia and reperfusion injury more than is generally believed, but blood vessels are more vulnerable, and such injury can impair perfusion of vitrifying cryoprotectant solution intended to eliminate ice formation in the brain. Forms of vascular and neuronal damage are reviewed, along with means of mitigating that damage. Recommendations are also made for preventing such damage.

  4. Phosphoinositide signaling in somatosensory neurons

    Science.gov (United States)

    Rohacs, Tibor

    2015-01-01

    Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in these neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  5. SILVER NANOPARTICLES IN THE SOLUTION OF THE PROBLEM OF DRUG RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    A. V. Zaharov

    2017-01-01

    Full Text Available The goal — a scientific evaluation of the effectiveness and safety of NHS in the treatment of experimental drug-resistant tuberculosis. Materials and methods. Used silver nanoparticles obtained by an electrochemical method. With a size of 5-60 nm, 120-270 kontsentratsiey- 1 mcm² and the size of the stabilizer shell — 2-5 nm. 750 crops studied Inhibitory activity of the silver nanoparticles in an isolated form and as part of a nanocomposite with chemotherapy in concentrations of 5; 25 and 50 mcg/ml. Defines the minimum inhibitory concentration of bactericidal nanoparticles composed of a nanocomposite with isoniazid. To evaluate the morphometry M.tuberculosis used atomic force microscopy. Toxicology nanopreparations studied 83 non-linear white mice and 146 white rats. Chemotherapeutic Activity nanopreparations determined on an experimental model of tuberculosis in 65 white male mice imbrednoy line BALB/c. Infectivity dose amount 5х106 colony forming units injected into the sinus venosus animal eyes. Isoniazid, nanoparticles and nanocomposite began administered 14 days after infection by intramuscular injection daily. Treatment efficacy was determined by comparing the evaluation criteria in the experimental and control groups of animals. Evaluated the following indicators: survival index, body mass index and weight of target organ, lesions index, index smear and inoculation of affected organs. Conducted pathological examination. Results. When using isoniazid, which had resistant pathogens, with silver nanoparticles full and significant inhibition of the growth of the M.tuberculosis observed in 49,2% of cases. When the concentration of the nanoparticles 5 mcg/ml in the composite bactericidal activity reached 91,3%. The minimum inhibitory concentration of silver nanoperticles in combination with isoniazid was 2,5 mcg/ml, the minimum bactericidal — 5 mcg /ml. There have been changes in the M.tuberculosis morphometry under the influence of the

  6. Learning and Stress Shape the Reward Response Patterns of Serotonin Neurons.

    Science.gov (United States)

    Zhong, Weixin; Li, Yi; Feng, Qiru; Luo, Minmin

    2017-09-13

    The ability to predict reward promotes animal survival. Both dopamine neurons in the ventral tegmental area and serotonin neurons in the dorsal raphe nucleus (DRN) participate in reward processing. Although the learning effects on dopamine neurons have been extensively characterized, it remains largely unknown how the response of serotonin neurons evolves during learning. Moreover, although stress is known to strongly influence reward-related behavior, we know very little about how stress modulates neuronal reward responses. By monitoring Ca 2+ signals during the entire process of Pavlovian conditioning, we here show that learning differentially shapes the response patterns of serotonin neurons and dopamine neurons in mice of either sex. Serotonin neurons gradually develop a slow ramp-up response to the reward-predicting cue, and ultimately remain responsive to the reward, whereas dopamine neurons increase their response to the cue but reduce their response to the reward. For both neuron types, the responses to the cue and the reward depend on reward value, are reversible when the reward is omitted, and are rapidly reinstated by restoring the reward. We also found that stressors including head restraint and fearful context substantially reduce the response strength of both neuron types, to both the cue and the reward. These results reveal the dynamic nature of the reward responses, support the hypothesis that DRN serotonin neurons signal the current likelihood of receiving a net benefit, and suggest that the inhibitory effect of stress on the reward responses of serotonin neurons and dopamine neurons may contribute to stress-induced anhedonia. SIGNIFICANCE STATEMENT Both serotonin neurons in the dorsal raphe and dopamine neurons in the ventral tegmental area are intimately involved in reward processing. Using long-term fiber photometry of Ca 2+ signals from freely behaving mice, we here show that learning produces a ramp-up activation pattern in serotonin neurons

  7. Hypothalamic survival circuits: blueprints for purposive behaviors.

    Science.gov (United States)

    Sternson, Scott M

    2013-03-06

    Neural processes that direct an animal's actions toward environmental goals are critical elements for understanding behavior. The hypothalamus is closely associated with motivated behaviors required for survival and reproduction. Intense feeding, drinking, aggressive, and sexual behaviors can be produced by a simple neuronal stimulus applied to discrete hypothalamic regions. What can these "evoked behaviors" teach us about the neural processes that determine behavioral intent and intensity? Small populations of neurons sufficient to evoke a complex motivated behavior may be used as entry points to identify circuits that energize and direct behavior to specific goals. Here, I review recent applications of molecular genetic, optogenetic, and pharmacogenetic approaches that overcome previous limitations for analyzing anatomically complex hypothalamic circuits and their interactions with the rest of the brain. These new tools have the potential to bridge the gaps between neurobiological and psychological thinking about the mechanisms of complex motivated behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Sperm Affects Head Sensory Neuron in Temperature Tolerance of Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Satoru Sonoda

    2016-06-01

    Full Text Available Tolerance to environmental temperature change is essential for the survival and proliferation of animals. The process is controlled by various body tissues, but the orchestration of activity within the tissue network has not been elucidated in detail. Here, we show that sperm affects the activity of temperature-sensing neurons (ASJ that control cold tolerance in Caenorhabditis elegans. Genetic impairment of sperm caused abnormal cold tolerance, which was unexpectedly restored by impairment of temperature signaling in ASJ neurons. Calcium imaging revealed that ASJ neuronal activity in response to temperature was decreased in sperm mutant gsp-4 with impaired protein phosphatase 1 and rescued by expressing gsp-4 in sperm. Genetic analysis revealed a feedback network in which ASJ neuronal activity regulates the intestine through insulin and a steroid hormone, which then affects sperm and, in turn, controls ASJ neuronal activity. Thus, we propose that feedback between sperm and a sensory neuron mediating temperature tolerance.

  9. Silver-functionalized carbon nanofiber composite electrodes for ibuprofen detection

    NARCIS (Netherlands)

    Manea, F.; Motoc, S.; Pop, A.; Remes, A.; Schoonman, J.

    2012-01-01

    The aim of this study is to prepare and characterize two types of silver-functionalized carbon nanofiber (CNF) composite electrodes, i.e., silver-decorated CNF-epoxy and silver-modified natural zeolite-CNF-epoxy composite electrodes suitable for ibuprofen detection in aqueous solution. Ag carbon

  10. Synthesis of nanosized silver colloids by microwave dielectric heating

    Indian Academy of Sciences (India)

    Silver nanosized crystallites have been synthesized in aqueous and polyols viz., ethylene glycol and glycerol, using a microwave technique. Dispersions of colloidal silver have been prepared by the reduction of silver nitrate both in the presence and absence of stabilizer poly(vinylpyrolidone) (PVP). It was observed that ...

  11. Fabrication and Antibacterial Performance of Nano-silver-Doped ...

    African Journals Online (AJOL)

    NICO

    enhancing the antibacterial activity of nanoparticles.15,16 In addi- tion, the antibacterial properties of nano-silver-doped filter paper against Escherichia coli have been studied.17 Silver ion release from sol-gel coatings has demonstrated antibacterial activ- ity against E. coli.18,19 Also, nano-silver-coated fabric inhibited the.

  12. Physicochemical properties of protein-modified silver nanoparticles in seawater

    Science.gov (United States)

    Zhong, Hangyue

    2013-10-01

    This study investigated the physicochemical properties of silver nanoparticles stabilized with casein protein in seawater. UV?vis spectrometry, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were applied to measure the stability of silver nanoparticles in seawater samples. The obtained results show an increased aggregation tendency of silver nanoparticles in seawater, which could be attributed its relatively high cation concentration that could neutralize the negatively charges adsorbed on the surface of silver nanoparticles and reduce the electrostatic repulsion forces between nanoparticles. Similarly, due to the surface charge screening process, the zeta potential of silver nanoparticles in seawater decreased. This observation further supported the aggregation behavior of silver nanoparticles. This study also investigated the dissolution of silver nanoparticles in seawater. Result shows that the silver nanoparticle dissolution in DI water is lower than in seawater, which is attributed to the high Cl? concentration present in seawater. As Cl? can react with silver and form soluble AgCl complex, dissolution of silver nanoparticles was enhanced. Finally, this study demonstrated that silver nanoparticles are destabilized in seawater condition. These results may be helpful in understanding the environmental risk of discharged silver nanoparticles in seawater conditions.

  13. Synthesis of silver impregnated carbon nanotubes and cyclodextrin ...

    African Journals Online (AJOL)

    Silver impregnated carbon nanotubes and cyclodextrin polymers were synthesised by first functionalising carbon nanotubes in a mixture of nitric and sulphuric acid before impregnating them with silver nanoparticles. The silver impregnated functionalised carbon nanotubes were then polymerised with β cyclodextrin using ...

  14. Biosynthesis of silver nanoparticles by marine bacterium, Idiomarina ...

    Indian Academy of Sciences (India)

    In this paper, we report the intracellular synthesis of silver nanoparticles (SNPs) by the highly silver-tolerant marine bacterium, Idiomarina sp. PR58-8 on exposure to 5mM silver nitrate. SNPs were characterized by UV-visible spectrophotometry, X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission ...

  15. A New Silver Complex with Ofloxacin – Preliminary Study

    Directory of Open Access Journals (Sweden)

    Rusu Aura

    2016-06-01

    Full Text Available Objective: Silver complexes of antibacterial quinolones have the potential advantage of combining the antibacterial activity of silver and fluoroquinolones. The objective of our study was the preparation and the preliminary physico-chemical characterization of a silver complex with ofloxacin.

  16. 25 CFR 304.3 - Classifying and marking of silver.

    Science.gov (United States)

    2010-04-01

    ... Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.3 Classifying and marking of silver. For the present the Indian Arts and Crafts Board... Government mark. All such marking of silver shall, for the present, be done by an agent of the Indian Arts...

  17. 25 CFR 304.7 - Eligibility of silver meeting standards.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Eligibility of silver meeting standards. 304.7 Section 304.7 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER... currently made in compliance with the standards of the Indian Arts and Crafts Board, other silver products...

  18. Pulsed laser excitation of phosphate stabilised silver nanoparticles

    Indian Academy of Sciences (India)

    Laser flash photolysis studies were carried out on two types of silver nanoparticles prepared by -radiolysis of Ag+ solutions in the presence of polyphosphate as the stabiliser. Type I silver nanoparticles displayed a surface plasmon band at 390 nm. Type II silver nanoparticles showed a 390 nm surface plasmon band with a ...

  19. Antimicrobial Activity of Silver Nanoparticles Synthesized by Marine ...

    African Journals Online (AJOL)

    In this work, in vitro biosynthesis of silver nanoparticles was achieved using AgNO3 as a substrate by L. plantrum isolated from mangrove rhizosphere region in South East Coast of India (Gulf of Mannar). The biosynthesis was faster within a minute of silver ion coming in contact with the cell filtrate. Presence of silver ...

  20. Synthesis of silver nanoparticles by sophorolipids: Effect of ...

    Indian Academy of Sciences (India)

    We report in situ synthesis of silver nanoparticles using biosurfactants called sophorolipids as reducing and capping agents. We further study the effect of temperature and the structure of sophorolipid on the size of silver nanoparticles obtained. The silver nanoparticles were characterized by UVvisible, transmission electron ...

  1. In vitro assessment of activity of graphene silver composite sheets ...

    African Journals Online (AJOL)

    Purpose: To synthesize graphene-based silver nanocomposites and evaluate their antimicrobial and anti-Tomato Bushy Stunt Virus (TBSV) activities. Methods: A graphene-based silver composite was prepared by adsorbing silver nanoparticles AgNPs to the surfaces of graphene oxide (GO) sheets. Scanning electron ...

  2. The Antifungal Activity and Cytotoxicity of Silver Containing Denture ...

    African Journals Online (AJOL)

    2015-10-30

    Oct 30, 2015 ... time- or silver-dependent cytotoxicity of PMMA denture base material containing ... dental materials.[14] Silver ions are biologically active,[15,16] so silver may have adverse effects on human cells.[17]. Although the literature reports various ..... vitro Candida colonization on acrylic resins and denture liners:.

  3. Aloysia triphylla essential oil as additive in silver catfish diet: Blood response and resistance against Aeromonas hydrophila infection.

    Science.gov (United States)

    Dos Santos, Alessandro C; Sutili, Fernando J; Heinzmann, Berta M; Cunha, Mauro A; Brusque, Isabel C M; Baldisserotto, Bernardo; Zeppenfeld, Carla C

    2017-03-01

    The essential oil of Aloysia triphylla (EOAT) is a promising product with potential use in aquaculture systems. This study evaluated hematological/biochemical responses and survival of silver catfish (Rhamdia quelen) fed a diet containing EOAT and infected by Aeromonas hydrophila. After 21 days of feeding trial, fish were infected with A. hydrophila following a 10-day period of observation. Blood collection was performed before and after the bacterial challenge. Dietary EOAT by itself seems to affect some blood parameters, decreasing total leukocyte, lymphocyte, and neutrophil counts and increasing total protein values. However, 2.0 mL EOAT/kg diet showed a possible potential protective effect after A. hydrophila infection, maintaining the evaluated parameters similar to basal values (from healthy fish before the feeding trial) and promoting survival of silver catfish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Mechanism of silver nanoparticle toxicity is dependent on dissolved silver and surface coating in Caenorhabditis elegans.

    Science.gov (United States)

    Yang, Xinyu; Gondikas, Andreas P; Marinakos, Stella M; Auffan, Melanie; Liu, Jie; Hsu-Kim, Heileen; Meyer, Joel N

    2012-01-17

    The rapidly increasing use of silver nanoparticles (Ag NPs) in consumer products and medical applications has raised ecological and human health concerns. A key question for addressing these concerns is whether Ag NP toxicity is mechanistically unique to nanoparticulate silver, or if it is a result of the release of silver ions. Furthermore, since Ag NPs are produced in a large variety of monomer sizes and coatings, and since their physicochemical behavior depends on the media composition, it is important to understand how these variables modulate toxicity. We found that a lower ionic strength medium resulted in greater toxicity (measured as growth inhibition) of all tested Ag NPs to Caenorhabditis elegans and that both dissolved silver and coating influenced Ag NP toxicity. We found a linear correlation between Ag NP toxicity and dissolved silver, but no correlation between size and toxicity. We used three independent and complementary approaches to investigate the mechanisms of toxicity of differentially coated and sized Ag NPs: pharmacological (rescue with trolox and N-acetylcysteine), genetic (analysis of metal-sensitive and oxidative stress-sensitive mutants), and physicochemical (including analysis of dissolution of Ag NPs). Oxidative dissolution was limited in our experimental conditions (maximally 15% in 24 h) yet was key to the toxicity of most Ag NPs, highlighting a critical role for dissolved silver complexed with thiols in the toxicity of all tested Ag NPs. Some Ag NPs (typically less soluble due to size or coating) also acted via oxidative stress, an effect specific to nanoparticulate silver. However, in no case studied here was the toxicity of a Ag NP greater than would be predicted by complete dissolution of the same mass of silver as silver ions.

  5. Neuron-specific splicing.

    Science.gov (United States)

    Hakim, Nor Hakimah Ab; Majlis, Burhanuddin Yeop; Suzuki, Hitoshi; Tsukahara, Toshifumi

    2017-03-22

    During pre-mRNA splicing events, introns are removed from the pre-mRNA, and the remaining exons are connected together to form a single continuous molecule. Alternative splicing is a common mechanism for the regulation of gene expression in eukaryotes. More than 90% of human genes are known to undergo alternative splicing. The most common type of alternative splicing is exon skipping, which is also known as cassette exon. Other known alternative splicing events include alternative 5' splice sites, alternative 3' splice sites, intron retention, and mutually exclusive exons. Alternative splicing events are controlled by regulatory proteins responsible for both positive and negative regulation. In this review, we focus on neuronal splicing regulators and discuss several notable regulators in depth. In addition, we have also included an example of splicing regulation mediated by the RBFox protein family. Lastly, as previous studies have shown that a number of splicing factors are associated with neuronal diseases such as Alzheime's disease (AD) and Autism spectrum disorder (ASD), here we consider their importance in neuronal diseases wherein the underlying mechanisms have yet to be elucidated.

  6. Comparison of silver nylon wound dressing and silver sulfadiazine in partial burn wound therapy.

    Science.gov (United States)

    Abedini, Fereydoon; Ahmadi, Abdollah; Yavari, Akram; Hosseini, Vahid; Mousavi, Sarah

    2013-10-01

    The study aims to perform a comparative assessment of two types of burn wound treatment. To do the assessment, patients with partial thickness burn wounds with total body surface area nylon wound dressing or silver sulfadiazine cream. Efficacy of treatment, use of analgesics, number of wound dressing change, wound infection and final hospitalisation cost were evaluated. The study showed silver nylon wound dressing significantly reduced length of hospital stay, analgesic use, wound infection and inflammation compared with silver sulfadiazine. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  7. In-Situ Silver Acetylide Silver Nitrate Explosive Deposition Measurements Using X-Ray Fluorescence.

    Energy Technology Data Exchange (ETDEWEB)

    Covert, Timothy Todd

    2014-09-01

    The Light Initiated High Explosive facility utilized a spray deposited coating of silver acetylide - silver nitrate explosive to impart a mechanical shock into targets of interest. A diagnostic was required to measure the explosive deposition in - situ. An X - ray fluorescence spectrometer was deployed at the facility. A measurement methodology was developed to measure the explosive quantity with sufficient accuracy. Through the use of a tin reference material under the silver based explosive, a field calibration relationship has been developed with a standard deviation of 3.2 % . The effect of the inserted tin material into the experiment configuration has been explored.

  8. Silver nanoparticle containing silk fibroin bionanotextiles

    Energy Technology Data Exchange (ETDEWEB)

    Calamak, Semih; Aksoy, Eda Ayse [Hacettepe University, Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy (Turkey); Erdogdu, Ceren; Sagıroglu, Meral [Hacettepe University, Department of Pharmaceutical Microbiology, Faculty of Pharmacy (Turkey); Ulubayram, Kezban, E-mail: ukezban@hacettepe.edu.tr [Hacettepe University, Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy (Turkey)

    2015-02-15

    Development of new generation bionanotextiles is an important growing field, and they have found applications as wound dressings, bandages, tissue scaffolds, etc. In this study, silver nanoparticle (AgNP) containing silk-based bionanotextiles were fabricated by electrospinning, and processing parameters were optimized and discussed in detail. AgNPs were in situ synthesized within fibroin nanofibers by UV reduction of silver ions to metallic silver. The influence of post-treatments via methanol treatment and glutaraldehyde (GA) vapor exhibited changes in the secondary structure of silk. Methanol treatment increased the tensile properties of fibers due to supported crystalline silk structure, while GA vapor promoted amorphous secondary structure. AgNP containing silk fibroin bionanotextiles had strong antibacterial activity against gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa.

  9. Silver containing sorbents: Physicochemical and biological properties

    Directory of Open Access Journals (Sweden)

    L.N. Rachkovskaya

    2016-06-01

    Full Text Available New silver containing sorbents, based on mineral carriers, such as alumina and silica systems with a meso- and macro- porous structure, have a higher mechanical resistance and, hydrophilic and hydrophobic chemical composition of the surface. These sorbents are easy to find and relatively inexpensive, compared to their known equivalents. They are furthermore characterised by high specific surface and simple preparation, whilst the addition of silver considerably increases their antiseptic activity. The results of research of the physical, chemical and biological properties of the developed substances, as well as bio-comparability of sorbents with biological tissues, are presented in this paper. The modified material acts simultaneously as the carrier for active substances to the area of therapeutic application and as a sorbent used to remove toxic agents from such areas. This approach led us to modify the sorbent, and prolong the delivery of substances such as silver, as an effective antibacterial and antimycotic agent.

  10. Modifications to the silver physical developer.

    Science.gov (United States)

    Burow, David; Seifert, Donald; Cantu, Antonio A

    2003-09-01

    The silver physical developer is currently the most successful reagent used for visualizing the water-insoluble components (e.g., lipids) of latent prints on porous surfaces. It is normally used after the amino acid visualizing reagents (e.g., ninhydrin and DFO) are used. This work found that the performance of the current formulation of silver physical developer is strongly reduced when the water used is changed from the usual distilled water to the more purified reverse osmosis/deionized (RO/DI) water. Based on numerous experiments involving the systematic variation of the component concentrations, the performance was restored and even improved by reducing the concentration of all the components (except that of the ferric salt) and by including malic acid in the formulation. These modifications resulted in a new silver physical developer formulation that performs as well as or better than the current formulation and is less expensive to make.

  11. Increased motor neuron resilience by small molecule compounds that regulate IGF-II expression.

    Science.gov (United States)

    Osborn, Teresia M; Beagan, Jonathan; Isacson, Ole

    2018-02-01

    The selective vulnerability of motor neurons in amyotrophic lateral sclerosis (ALS) is evident by sparing of a few subpopulations during this fast progressing and debilitating degenerative disease. By studying the gene expression profile of resilient vs. vulnerable motor neuron populations we can gain insight in what biomolecules and pathways may contribute to the resilience and vulnerability. Several genes have been found to be differentially expressed in the vulnerable motor neurons of the cervical spinal cord as compared to the spared motor neurons in CNIII/IV. One gene that is differentially expressed and present at higher levels in less vulnerable motor neurons is insulin-like growth factor II (IGF-II). The motor neuron protective effect of IGF-II has been demonstrated both in vitro and in SOD1 transgenic mice. Here, we have screened a library of small molecule compounds and identified inducers of IGF-II mRNA and protein expression. Several identified compounds significantly protected motor neurons from glutamate excitotoxicity in vitro. One of the compounds, vardenafil, resulted in a complete motor neuron protection, an effect that was reversed by blocking receptors of IGF-II. When administered to naïve rats vardenafil was present in the cerebrospinal fluid and increased IGF-II mRNA expression in the spinal cord. When administered to SOD1 transgenic mice, there was a significant delay in motor symptom onset and prolonged survival. Vardenafil also increased IGF-II mRNA and protein levels in motor neurons derived from healthy subject and ALS patient iPSCs, activated a human IGF-II promoter and improved survival of ALS-patient derived motor neurons in culture. Our findings suggest that modulation of genes differentially expressed in vulnerable and resilient motor neurons may be a useful therapeutic approach for motor neuron disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    OpenAIRE

    Eder, Anja; Bading, Hilmar

    2007-01-01

    Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nuc...

  13. In Vivo AAV1 Transduction With hRheb(S16H) Protects Hippocampal Neurons by BDNF Production

    OpenAIRE

    Jeon, Min-Tae; Nam, Jin Han; Shin, Won-Ho; Leem, Eunju; Jeong, Kyoung Hoon; Jung, Un Ju; Bae, Young-Seuk; Jin, Young-Ho; Kholodilov, Nikolai; Burke, Robert E.; Lee, Seok-Geun; Jin, Byung Kwan; Kim, Sang Ryong

    2015-01-01

    Recent evidence has shown that Ras homolog enriched in brain (Rheb) is dysregulated in Alzheimer's disease (AD) brains. However, it is still unclear whether Rheb activation contributes to the survival and protection of hippocampal neurons in the adult brain. To assess the effects of active Rheb in hippocampal neurons in vivo, we transfected neurons in the cornu ammonis 1 (CA1) region in normal adult rats with an adeno-associated virus containing the constitutively active human Rheb (hRheb(S16...

  14. Percutaneous penetration of silver from a silver containing garment in healthy volunteers and patients with atopic dermatitis

    NARCIS (Netherlands)

    Pluut, Olivier A.; Bianco, Carlotta; Jakasa, Ivone; Visser, Maaike J.; Krystek, Petra; Larese-Filon, Francesca; Rustemeyer, Thomas; Kezic, Sanja

    2015-01-01

    Human data on dermal absorption of silver under "in use" scenario are scarce which hampers health risk assessment. The main objective of the present study was to determine percutaneous penetration of silver after dermal exposure to silver containing garment in healthy individuals and atopic

  15. Effects of Chemically Doped Bioactive Borate Glass on Neuron Regrowth and Regeneration.

    Science.gov (United States)

    Gupta, Brinda; Papke, Jason B; Mohammadkhah, Ali; Day, Delbert E; Harkins, Amy B

    2016-12-01

    Peripheral nerve injuries present challenges to regeneration. Currently, the gold standard for nerve repair is an autograft that results in another region of the body suffering nerve damage. Previously, bioactive borate glass (BBG) has been studied in clinical trials to treat patients with non-healing wounds, and we have reported that BBG is conducive for soft tissue repair. BBG provides structural support, degrades in a non-cytotoxic manner, and can be chemically doped. Here, we tested a wide range of chemical compounds that are reported to have neuroprotective characteristics to promote regeneration of peripheral neurons after traumatic injury. We hypothesized that chemical dopants added in trace amounts to BBG would improve neuronal survival and neurite outgrowth from dorsal root ganglion (DRG) explants. We measured neurite outgrowth from whole DRG explants, and survival rates of dissociated neurons and support cells that comprise the DRG. Results show that chemically doped BBGs have differentially variable effects on neuronal survival and outgrowth, with iron, gallium, and zinc improving outgrowth of neurons, and iodine causing the most detriment to neurons. Because chemically doped BBGs support increased nerve regrowth and survival, they show promise for use in peripheral nerve regeneration.

  16. Transduction of PACAP38 protects primary cortical neurons from neurotoxic injury.

    Science.gov (United States)

    Sanchez, Alma; Chiriva-Internati, Maurizo; Grammas, Paula

    2008-12-19

    Neurotrophic factors such as pituitary adenylate cyclase activating polypeptide (PACAP38) are promising therapeutics for neurodegenerative diseases. However, delivery of trophic factors into brain neurons remains a challenge. The objective of this study is to determine whether adeno-associated virus (AAV) can mediate PACAP38 gene delivery into neurons in vitro and if transduction of AAV/PACAP38 into cortical neurons protects cells against neurotoxic insult. Primary cortical neuronal cultures are transduced with rAAV/PACAP38/GFP and cell survival against the nitric oxide releasing neurotoxin sodium nitroprusside (SNP) determined. GFP expression, a surrogate marker for successful transduction, is detected using fluorescent microscopy. The results show expression of GFP transgene and AAV capsid proteins in neurons. PACAP38 transduction significantly increases cell survival of neurons exposed to SNP. These results support the feasibility of using AAV-mediated delivery of PACAP38 to enhance neuronal survival and suggest that AAV-delivered PACAP38 maybe a therapeutic strategy for neurodegenerative diseases.

  17. Recovery of silver from CEPOD anolyte solutions

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, D.L.; Surma, J.E.; Alexander, D.L.; Shade, E.H.; Matheson, J.D.; Cochran, D.L.; Wheelwright, E.J. [Pacific Northwest Lab., Richland, WA (United States); Boyd, T. [EG& G Rocky Flats Plant, Golden, CO (United States)

    1994-09-01

    The process known as Catalyzed Electrochemical Plutonium Oxide Dissolution (CEPOD) has been shown effective for removing plutonium from a variety of residues and solids. This process involves the electrochemical oxidation of PuO{sub 2} (and other Pu species) to (PuO{sub 2}){sup 2+}, and dissolution of the latter species in the anode solution (anolyte). Silver is used to transfer charge from the electrodes to the solid Pu oxide. Ag (1) is oxidized at the anode to Ag(II) and carried by the solution to the plutonium oxide solids, where the silver and oxide undergo a redox reaction that converts Pu(IV) to Pu(VI), and Ag(II) to Ag(I). Other metal ions [such as Ce(IV) and Co(III)] may also be used for this charge transfer, but have been found to be less effective than silver. The same process may be used to destroy various organic materials (such as paper and wood, oil and fuels, and synthetic polymer materials) by complete oxidation to CO{sub 2} or H{sub 2}O, for example. Upon completion of a CEPOD dissolver run, the anolyte may be processed to remove solution species of interest (i.e., Pu), or the anolyte may be recycled, or disposed. Because silver is a Resource Conservation and Recovery Act (RCRA) land ban material, it must be removed from waste streams. Preliminary experiments, completed in FY 1991, demonstrated a simple, effective technique for silver removal from solutions. Ascorbic acid (C{sub 6}H{sub 8}O{sub 6}) Was Used to reduce silver ion to metallic silver, which precipitates from solution. The process was demonstrated effective on a bench scale using samples of actual CEPOD anolyte. Further experiments, in FY 1993, optimized these parameters and demonstrated the effectiveness of the technique on CEPOD anolyte on a larger, process scale (liters of solution). This report describes both the preliminary bench-scale experiments and the more recent process-scale experiments. The results are also compared to electro-deposition, another method of silver ion removal.

  18. Fluorescent DNA Stabilized Silver Nanoclusters as Biosensors

    Directory of Open Access Journals (Sweden)

    Alfonso Latorre

    2013-01-01

    Full Text Available DNA stabilized fluorescent silver nanoclusters are promising materials, of which fluorescent properties can be exploited to develop sensors. Particularly, the presence of a DNA strand in the structure has promoted the development of gene sensors where one part of the sensor is able to recognize the target gene sequence. Moreover, since oligonucleotides can be designed to have binding properties (aptamers a variety of sensors for proteins and cells have been developed using silver nanoclusters. In this review the applications of this material as sensors of different biomolecules are summarized.

  19. Mineral resource of the month: silver

    Science.gov (United States)

    Katrivanos, Florence C.

    2015-01-01

    Silver, one of the eight precious or noble metals, has been used extensively throughout recorded history for various medical purposes, ornaments and utensils, and for its intrinsic value as the basis for trade and monetary systems. Silver has played a significant role in world history, financing a Greek victory over the Persians in 480 B.C., helping Spain become a world power in the 16th and 17th centuries, and helping fund the Union forces during the U.S. Civil War, to give a few examples.

  20. IgLON Cell Adhesion Molecules Are Shed from the Cell Surface of Cortical Neurons to Promote Neuronal Growth*

    Science.gov (United States)

    Sanz, Ricardo; Ferraro, Gino B.; Fournier, Alyson E.

    2015-01-01

    Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons. PMID:25538237

  1. IgLON cell adhesion molecules are shed from the cell surface of cortical neurons to promote neuronal growth.

    Science.gov (United States)

    Sanz, Ricardo; Ferraro, Gino B; Fournier, Alyson E

    2015-02-13

    Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. CALBINDIN CONTENT AND DIFFERENTIAL VULNERABILITY OF MIDBRAIN EFFERENT DOPAMINERGIC NEURONS IN MACAQUES

    Directory of Open Access Journals (Sweden)

    Iria G Dopeso-Reyes

    2014-12-01

    Full Text Available Calbindin (CB is a calcium binding protein reported to protect dopaminergic neurons from degeneration. Although a direct link between CB content and differential vulnerability of dopaminergic neurons has long been accepted, factors other than CB have also been suggested, particularly those related to the dopamine transporter. Indeed, several studies have reported that CB levels are not causally related to the differential vulnerability of dopaminergic neurons against neurotoxins. Here we have used dual stains for tyrosine hydroxylase (TH and CB in 3 control and 3 MPTP-treated monkeys to visualize dopaminergic neurons in the ventral tegmental area (VTA and in the dorsal and ventral tiers of the substantia nigra pars compacta (SNcd and SNcv co-expressing TH and CB. In control animals, the highest percentages of co-localization were found in VTA (58.2%, followed by neurons located in the SNcd (34.7%. As expected, SNcv neurons lacked CB expression. In MPTP-treated animals, the percentage of CB-ir/TH-ir neurons in the VTA was similar to control monkeys (62.1%, whereas most of the few surviving neurons in the SNcd were CB-ir/TH-ir (88.6%. Next, we have elucidated the presence of CB within identified nigrostriatal and nigroextrastriatal midbrain dopaminergic projection neurons. For this purpose, two control monkeys received one injection of Fluoro-Gold into the caudate nucleus and one injection of cholera toxin (CTB into the postcommissural putamen, whereas two more monkeys were injected with CTB into the internal division of the globus pallidus. As expected, all the nigrocaudate- and nigroputamen-projecting neurons were TH-ir, although surprisingly, all of these nigrostriatal-projecting neurons were negative for CB. Furthermore, all the nigropallidal-projecting neurons co-expressed both TH and CB. In summary, although CB-ir dopaminergic neurons seem to be less prone to MPTP-induced degeneration, our data clearly demonstrated that these neurons are not

  3. Patterning human neuronal networks on photolithographically engineered silicon dioxide substrates functionalized with glial analogues.

    Science.gov (United States)

    Hughes, Mark A; Brennan, Paul M; Bunting, Andrew S; Cameron, Katherine; Murray, Alan F; Shipston, Mike J

    2014-05-01

    Interfacing neurons with silicon semiconductors is a challenge being tackled through various bioengineering approaches. Such constructs inform our understanding of neuronal coding and learning and ultimately guide us toward creating intelligent neuroprostheses. A fundamental prerequisite is to dictate the spatial organization of neuronal cells. We sought to pattern neurons using photolithographically defined arrays of polymer parylene-C, activated with fetal calf serum. We used a purified human neuronal cell line [Lund human mesencephalic (LUHMES)] to establish whether neurons remain viable when isolated on-chip or whether they require a supporting cell substrate. When cultured in isolation, LUHMES neurons failed to pattern and did not show any morphological signs of differentiation. We therefore sought a cell type with which to prepattern parylene regions, hypothesizing that this cellular template would enable secondary neuronal adhesion and network formation. From a range of cell lines tested, human embryonal kidney (HEK) 293 cells patterned with highest accuracy. LUHMES neurons adhered to pre-established HEK 293 cell clusters and this coculture environment promoted morphological differentiation of neurons. Neurites extended between islands of adherent cell somata, creating an orthogonally arranged neuronal network. HEK 293 cells appear to fulfill a role analogous to glia, dictating cell adhesion, and generating an environment conducive to neuronal survival. We next replaced HEK 293 cells with slower growing glioma-derived precursors. These primary human cells patterned accurately on parylene and provided a similarly effective scaffold for neuronal adhesion. These findings advance the use of this microfabrication-compatible platform for neuronal patterning. Copyright © 2013 Wiley Periodicals, Inc.

  4. Autometallography: tissue metals demonstrated by a silver enhancement kit

    DEFF Research Database (Denmark)

    Danscher, G; Nørgaard, J O; Baatrup, E

    1987-01-01

    In biological tissue, minute accumulations of gold, silver, mercury and zinc can be visualized by a technique whereby metallic silver is precipitated on tiny accumulations of the two noble metals, or on selenites or sulphides of all four metals. In the present study a silver enhancement kit, prim...... methods and for demonstration of gold, silver, and mercury in tissues from animals intravitally exposed to these metals. It can also be used for counterstaining silver treated osmium fixed tissues embedded in plastic. Udgivelsesdato: 1987-null...

  5. Management of silver fir (Abies alba Mill.) in Slovenia

    OpenAIRE

    Bončina, Andrej; Ficko, Andrej; Klopčič, Matija; Matijašič, Dragan; Poljanec, Aleš

    2009-01-01

    In the paper, we analysed the structure and developmental characteristics of forest stands with silver fir in Slovenia, the management and cut in four forest site strata, where silver fir occurs. We used databases from the Slovenia Forest Service. In growing stock (GS) of silver fir, large (dbh=30-49cm) and very large (d=50 cm and more) diameter trees account for 84.9 % at the national level. The highest share of very large diameter silver fir trees (45 %) is in Dinaric silver fir forests and...

  6. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  7. Astroglial networks promote neuronal coordination.

    Science.gov (United States)

    Chever, Oana; Dossi, Elena; Pannasch, Ulrike; Derangeon, Mickael; Rouach, Nathalie

    2016-01-12

    Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30- and connexin 43-deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior. Our data thus provide molecular and biophysical evidence predicting selective astroglial gap junction inhibitors as anticonvulsive drugs. Copyright © 2016, American Association for the Advancement of Science.

  8. Induction of Neuronal Cell Death by Paraneoplastic Ma1 Antigen

    Science.gov (United States)

    Chen, Huai-Lu; D’Mello, Santosh R.

    2016-01-01

    Paraneoplastic Ma1 (PNMA1) is a member of a family of proteins involved in an autoimmune disorder called paraneoplastic neurological syndrome. Although it is widely expressed in brain, nothing is known about the function of PNMA1 in neurons. We find that PNMA1 expression is highest in the perinatal brain, a period during which developmentally regulated neuronal death occurs. PNMA1 expression increases in cerebellar granule neurons (CGNs) induced to die by low potassium (LK) and in cortical neurons following homocysteic acid (HCA) treament. Elevated PNMA1 expression is also observed in the degenerating striatum in two separate mouse models of Huntington’s disease, the R6/2 transgenic model and the 3-nitropropionic acid-induced chemical model. Suppression of endogenous PNMA1 expression inhibits LK-induced neuronal apoptosis. Ectopic expression of PNMA1 promotes apoptosis even in medium containing high potassium, a condition that normally ensures survival of CGNs. Deletion of the N-terminal half of the PNMA1 protein abrogates its apoptotic activity, whereas deletion of the C-terminal half renders the protein more toxic. Within the N-terminal half, the ability to induce neuronal death depends on the presence of a BH3-like domain. In addition to being necessary for apoptosis, the BH3-like domain is necessary for self-association of PNMA1. Apoptosis by PNMA1 expression is inhibited by overexpression of Bcl2, suggesting that PNMA1-induced neuronal death may depend on the binding of a proapoptotic member of the Bcl2 family to the BH3 domain. Taken together, our results suggest that PNMA1 is a proapoptotic protein in neurons, elevated expression of which may contribute to neurodegenerative disorders. PMID:20936693

  9. NT2 derived neuronal and astrocytic network signalling.

    Directory of Open Access Journals (Sweden)

    Eric J Hill

    Full Text Available A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

  10. Staining of dead neurons by the Golgi method in autopsy material.

    Science.gov (United States)

    Baloyannis, Stavros J

    2015-01-01

    Golgi silver impregnation techniques remain ideal methods for the visualization of the neurons as a whole in formalin fixed brains and paraffin sections, enabling to obtain insight into the morphological and morphometric characters of the dendritic arbor, and the estimation of the morphology of the spines and the spinal density, since they delineate the profile of nerve cells with unique clarity and precision. In addition, the Golgi technique enables the study of the topographic relationships between neurons and neuronal circuits in normal conditions, and the following of the spatiotemporal morphological alterations occurring during degenerative processes. The Golgi technique has undergone many modifications in order to be enhanced and to obtain the optimal and maximal visualization of neurons and neuronal processes, the minimal precipitations, the abbreviation of the time required for the procedure, enabling the accurate study and description of specific structures of the brain. In the visualization of the sequential stages of the neuronal degeneration and death, the Golgi method plays a prominent role in the visualization of degenerating axons and dendrites, synaptic “boutons,” and axonal terminals and organelles of the cell body. In addition, new versions of the techniques increases the capacity of precise observation of the neurofibrillary degeneration, the proliferation of astrocytes, the activation of the microglia, and the morphology of capillaries in autopsy material of debilitating diseases of the central nervous system.

  11. Multinationals and plant survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2010-01-01

    The aim of this paper is twofold: first, to investigate how different ownership structures affect plant survival, and second, to analyze how the presence of foreign multinational enterprises (MNEs) affects domestic plants’ survival. Using a unique and detailed data set on the Swedish manufacturing...... sector, I am able to separate plants into those owned by foreign MNEs, domestic MNEs, exporting non-MNEs, and purely domestic firms. In line with previous findings, the result, when conditioned on other factors affecting survival, shows that foreign MNE plants have lower survival rates than non......-MNE plants. However, separating the non-MNEs into exporters and non-exporters, the result shows that foreign MNE plants have higher survival rates than non-exporting non-MNEs, while the survival rates of foreign MNE plants and exporting non-MNE plants do not seem to differ. Moreover, the simple non...

  12. Silver surface enrichment of silver-copper alloys: a limitation for the analysis of ancient silver coins by surface techniques

    Science.gov (United States)

    Beck, L.; Bosonnet, S.; Réveillon, S.; Eliot, D.; Pilon, F.

    2004-11-01

    The surface enrichment of archaeological silver-copper alloys has been recognized for many years. However, the origin of this enrichment is not well defined and many hypotheses have been put forward to account for this behaviour: segregation of the components during casting, deliberate thermal and/or chemical post-treatment, abrasion or corrosion. Among the hypotheses mentioned above, we have focused our study on the first step of coin manufacturing. Replications of silver-copper standards of various compositions ranging from 30% to 80% Ag, reflecting the composition of silver blanks, have been produced. Metallographic examination, PIXE and SEM-EDS have been used for the characterization of each sample. A model of the direct enrichment has been established. This model allows us to propose a relationship between the surface composition and the silver content of the core. Comparison with data of Roman coins from the Roman site of Châteaubleau (France) and from the literature and consequences for the analyses of ancient coins by surface methods are presented.

  13. Egr3 dependent sympathetic target tissue innervation in the absence of neuron death.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available Nerve Growth Factor (NGF is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax-deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appears to effect target tissue innervation heterogeneously. In some tissues, such as heart, spleen, bowel, kidney, pineal gland and the eye, Egr3 is essential for normal innervation, whereas in other tissues such as lung, stomach, pancreas and liver, Egr3 appears to have little role in innervation. Moreover, in salivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that abnormal target tissue innervation is not due to deregulation of these neurotrophins in target tissues. Taken together, these results clearly demonstrate a role for Egr3 in mediating sympathetic target tissue innervation that is independent of neuron survival or neurotrophin deregulation.

  14. Motor neurons and the generation of spinal motor neurons diversity

    OpenAIRE

    Nicolas eStifani

    2014-01-01

    Motor neurons (MNs) are neuronal cells located in the central nervous system (CNS) controlling a variety of downstream targets. This function infers the existence of MN subtypes matching the identity of the targets they innervate. To illustrate the mechanism involved in the generation of cellular diversity and the acquisition of specific identity, this review will focus on spinal motor neurons (SpMNs) that have been the core of significant work and discoveries during the last decades. SpMNs a...

  15. Correlative fluorescence and electron microscopy of biocytin-filled neurons with a preservation of the postsynaptic ultrastructure.

    Science.gov (United States)

    Morozov, Youri; Khalilov, Ilgam; Ben-Ari, Yehezkel; Represa, Alfonso

    2002-05-30

    Several techniques enable to inject intracellularly neurons with dyes and to use light and electron microscopy to correlate the physiological data with the morphological properties of the neuron. However, the ultrastructure of the neuron is usually obscured by the injected dye thus notably precluding the analysis of the postsynaptic specialisation and that of the other organelles. To overcome this problem, we have developed a technique based on fluorophore- and ultra small gold-conjugated streptavidins. We report, that this method facilitates the identification of intracellular organelles of the biocytin-filled neuron and of postsynaptic densities. This method is valid for the study of early postnatal neurons that are particularly refractory to this type of analysis. The procedure introduced here consists of the following steps: (1) injection of biocytin into the neuron by a patch-clamp pipette, (2) aldehyde fixation, (3) reaction with a fluorophore-conjugated streptavidin, (4) analysis with a fluorescence microscope, (5) formation of avidin-biotin complexes (ABC), (6) reaction with an ultra small gold-conjugated streptavidin, (7) silver enhancement of gold, (8) postfixation with osmium tetroxide and embedding in resin, (9) ultrathin sectioning and analysis with an electron microscope. Using this method, we show that in early postnatal hippocampal neurons, that have been injected with biocytine, it is possible to determine the morphology of the dendritic and axonal trees (including very thin details such as spines and filopodia) and to identify the localisation of the symmetric and asymmetric synapses on dendrites of the injected neuron.

  16. Bioaccumulation of silver in Daphnia magna:Waterborne and dietary exposure to nanoparticles and dissolved silver

    NARCIS (Netherlands)

    Ribeiro, Fabianne; van Gestel, C.A.M.; Pavlaki, M.D.; Azevedo, S.; Soares, A.M.V.M.; Loureiro, S.

    2017-01-01

    Silver nanoparticles (Ag-NP) are incorporated into commercial products as antimicrobial agents, which potentiate their emission to the environment. The toxicity of Ag-NP has been associated with the release of Ag ions (Ag

  17. Free amino acids as indicators of nutritional status of silver bream (Vimba vimba), when using commercial and purified diets.

    Science.gov (United States)

    Kwasek, Karolina; Zhang, Yongfang; Hliwa, Piotr; Gomułka, Piotr; Ostaszewska, Teresa; Dabrowski, Konrad

    2009-06-01

    Studies on larval rearing of silver bream (Vimba vimba), a migratory cyprinid fish have addressed on limited scale larval and juvenile rearing using commercial and semipurified diets along with live feeds, such as brine shrimp Artemia nauplii. The objectives of the present study were (1) to determine whether experimental, protein-, peptide-, free amino acid-based diets are adequate for larval silver bream, a stomachless fish, (2) to evaluate whether commercial and purified diets are comparable as the first/exclusive feed for growth and survival of silver bream, and (3) to examine whether free amino acid concentrations in fish body are potential indicators of availability of amino acid sources. We report here the differences in diets acceptance, fish growth and diet utilization in silver bream in comparison to other cyprinid fishes. We specifically address the response in free amino acids in the body to dietary treatments. Experimental diets included: a commercial Aglo Norse feed, casein-gelatin based diet (CG), free amino acid mixture diet (FAA), dipeptide (PP), dipeptide-protein (PP50) based diet, and dipeptide diet without arginine (NoArg). In addition, live Artemia were offered to 3 groups and "fasting" control treatment was included during 3 week long trial. Fish offered Artemia overperformed those offered formulated diets both in terms of mass (80.7+/-26.3 mg) and survival (97.2%). We also indicate that commercial and purified diets are comparable as the first/exclusive feed for growth and survival of silver bream. Our experiment also showed that the whole body free amino acid concentrations of 9 indispensable amino acids (IDAA) out of 10 (His, Thr, Arg, Val, Met, Ile, Leu, Trp, Lys) in the PP50 group was the highest among 7 diet treatments and the totalfree amino acid concentration, total dispensable amino acids (DAA) and total IDAA of the PP50 diet fed fish showed the same trend. This may indicate that diets based on 50% of dipeptides and 50% of protein are

  18. Synthesis and characterization of silver nanoparticles in AOT microemulsion system

    Science.gov (United States)

    Zhang, Wanzhong; Qiao, Xueliang; Chen, Jianguo

    2006-11-01

    Colloidal silver nanoparticles have been synthesized in water-in-oil microemulsion using silver nitrate solubilized in the water core of one microemulsion as source of silver ions, hydrazine hydrate solubilized in the water core of another microemulsion as reducing agent, dodecane as the oil phase, sodium bis(2-ethylhexyl) sulfosuccinate (AOT) as the surfactant. The UV-vis absorption spectra and transmission electron microscopy (TEM) have been used to trace the growth process and elucidate the structure of the silver nanoparticles. UV-vis spectra show that the Ag4+ intermediates formed at early stages of the reaction and then the clusters grow or aggregate to larger nanoparticles. TEM micrographs confirm that the silver nanoparticles are all spherical. The resulting particles have a very narrow size distribution. Meanwhile, the diameter size of the particles is so small that the smallest mean diameter is only 1.6 nm. IR results show that the surfactant molecules are strongly adsorbed on the surface of silver particles through a coordination bond between the silver atom and the sulfonic group of AOT molecules, which endows the particles with a good stability in oil solvents. As dodecane is used as oil solvent to prepare silver nanoparticles, the formed nano-silver sol is almost nontoxic. As a result, the silver nanoparticles need not be separated from the reaction solution and the silver sol may be directly used in antibacterial fields.

  19. Nasal neuron PET imaging quantifies neuron generation and degeneration

    National Research Council Canada - National Science Library

    Van de Bittner, Genevieve C; Riley, Misha M; Cao, Luxiang; Ehses, Janina; Herrick, Scott P; Ricq, Emily L; Wey, Hsiao-Ying; O'Neill, Michael J; Ahmed, Zeshan; Murray, Tracey K; Smith, Jaclyn E; Wang, Changning; Schroeder, Frederick A; Albers, Mark W; Hooker, Jacob M

    2017-01-01

    .... Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality...

  20. Latent synthesis of electrically conductive surface-silvered polyimide films.

    Science.gov (United States)

    Davis, Luke M; Abelt, Christopher J; Scott, Joseph L; Orlova, Evguenia; Thompson, David W

    2009-01-01

    A facile ambient temperature route to the fabrication of surface silver-metallized polyimide films is described. Silver(I) trifluoromethanesulfonate or silver(I) nitrate and a polyimide, derived from 2,2-bis(3,4-dicarboxyphenyl)hexafluoropropane dianhydride and an equimolar amount of 4,4'-oxydianiline and 3,5-diaminobenzoic acid, were dissolved together in dimethylacetamide. Silver(I)-doped films were prepared at thicknesses of 25-40 microm and depleted of solvent by evaporation at ambient temperature and low humidity. The silver(I)-ion-containing films were then treated with aqueous solutions of the reducing agents hydrazine hydrate and hydroxylamine, which brought forth surface-silvered films exhibiting conductivity on the order of bulk polycrystalline silver accompanied by modest-to-high specular reflectivity.

  1. Phytochemical Synthesis and Preliminary Characterization of Silver Nanoparticles Using Hesperidin

    Directory of Open Access Journals (Sweden)

    Anish Stephen

    2013-01-01

    Full Text Available This paper is the first of its kind for development of rapid and ecofriendly method for synthesis of silver nanoparticles from aqueous solution of silver nitrate using the flavonoid “hesperidin” and optimization of the methodology. There is formation of stable spherical silver nanoparticles in the size range of 20–40 nm. Optimization of methodology in terms of concentration of reactants and pH of the reaction mixture reduced the reaction time for silver nanoparticle formation to 2 mins. Silver nanoparticles (AgNPs were characterized by UV-Vis spectroscopy and transmission electron microscopy (TEM. UV-vis spectroscopy derived spectrum demonstrated a peak of 430 nm which corresponds to the plasmon absorbance of silver nanoparticles. Transmission electron microscopy revealed spherical shaped silver nanoparticles in the size range of 20–40 nm.

  2. Silver nanosystems for photoacoustic imaging and image-guided therapy

    Science.gov (United States)

    Homan, Kimberly; Shah, Jignesh; Gomez, Sobeyda; Gensler, Heidi; Karpiouk, Andrei; Brannon-Peppas, Lisa; Emelianov, Stanislav

    2010-01-01

    Due to their optical absorption properties, metallic nanoparticles are excellent photoacoustic imaging contrast agents. A silver nanosystem is presented here as a potential contrast agent for photoacoustic imaging and image-guided therapy. Currently, the nanosystem consists of a porous silver layer deposited on the surface of spherical silica cores ranging in diameter from 180 to 520 nm. The porous nature of the silver layer will allow for release of drugs or other therapeutic agents encapsulated in the core in future applications. In their current PEGylated form, the silver nanosystem is shown to be nontoxic in vitro at concentrations of silver up to 2 mg∕ml. Furthermore, the near-infrared absorbance properties of the nanosystem are demonstrated by measuring strong, concentration-dependent photoacoustic signal from the silver nanosystem embedded in an ex vivo tissue sample. Our study suggests that silver nanosystems can be used as multifunctional agents capable of augmenting image-guided therapy techniques. PMID:20459238

  3. Selective separation of silver(I) by novel substituted thiourea

    Energy Technology Data Exchange (ETDEWEB)

    Khan, A. [Pakistan Inst. of Nuclear Science and Technology (PINSTECH), Islamabad (Pakistan). Chemistry Div.

    2007-07-01

    The extraction of silver(I) from nitric acid solutions using naphthyl substituted thiourea such as 1-naphthylthiourea (ANTU) has been studied. Different variables: equilibration time, aqueous pH, chloride and extractant concentrations and organic phase diluent that could affect the extraction system were evaluated at 28.0 {+-} 2.0 C. It was found that silver is quantitatively extracted by ANTU over the entire studied range of nitric acid concentration. Extraction of silver by ANTU is fast and equilibration was achieved in less than five minutes. Experimental data relating to silver have been analysed to determine the stoichiometry of the extracted species. Effect of foreign ions on the extraction of silver was carried out. Recycling capacity of the extractant was also studied. Thiourea and EDTA solutions were found suitable for > 99% stripping of extracted silver(I). The reagent has been found to have high selectivity for silver against copper, cadmium, nickel, cobalt, hafnium, zirconium and europium. (orig.)

  4. Yeast-derived biosynthesis of silver/silver chloride nanoparticles and their antiproliferative activity against bacteria

    OpenAIRE

    Eugenio, Mateus; Müller, Nathalia; Frasés, Susana; Almeida-Paes, Rodrigo; Lima, Luís Maurício T.R.; Lemgruber, Leandro; Farina, Marcos; de Souza, Wanderley; Sant'Anna, Celso

    2016-01-01

    Here, we provide the first evidence of yeast strains assisted Ag/AgCl-NPs production in vitro. The formed nanoparticles were characterized by spectroscopic and electron microscopy approaches. UV-vis supported the biosynthesis. TEM analysis evidenced that the nanoparticles mainly presented a circular shape and their diameters varied mostly being in the range 2 to 10 nm. XRD analysis showed a crystalline structure, with diffraction peaks corresponding to metallic silver and silver chloride nano...

  5. A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

    Science.gov (United States)

    Bachler, Gerald; von Goetz, Natalie; Hungerbühler, Konrad

    2013-01-01

    Silver is a strong antibiotic that is increasingly incorporated into consumer products as a bulk, salt, or nanosilver, thus potentially causing side-effects related to human exposure. However, the fate and behavior of (nano)silver in the human body is presently not well understood. In order to aggregate the existing experimental information, a physiologically based pharmacokinetic model (PBPK) was developed in this study for ionic silver and nanosilver. The structure of the model was established on the basis of toxicokinetic data from intravenous studies. The number of calibrated parameters was minimized in order to enhance the predictive capability of the model. We validated the model structure for both silver forms by reproducing exposure conditions (dermal, oral, and inhalation) of in vivo experiments and comparing simulated and experimentally assessed organ concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption fraction was estimated based on the blood silver concentration of the respective experimental data set. In all of the cases examined, the model could successfully predict the biodistribution of ionic silver and 15–150 nm silver nanoparticles, which were not coated with substances designed to prolong the circulatory time (eg, polyethylene glycol). Furthermore, the results of our model indicate that: (1) within the application domain of our model, the particle size and coating had a minor influence on the biodistribution; (2) in vivo, it is more likely that silver nanoparticles are directly stored as insoluble salt particles than dissolve into Ag+; and (3) compartments of the mononuclear phagocytic system play a minor role in exposure levels that are relevant for human consumers. We also give an example of how the model can be used in exposure and risk assessments based on five different exposure scenarios, namely dietary intake, use of three separate consumer products, and occupational exposure. PMID:24039420

  6. Antimicrobial activity of biogenic silver nanoparticles, and silver chloride nanoparticles: an overview and comments.

    Science.gov (United States)

    Durán, Nelson; Nakazato, Gerson; Seabra, Amedea B

    2016-08-01

    The antimicrobial impact of biogenic-synthesized silver-based nanoparticles has been the focus of increasing interest. As the antimicrobial activity of nanoparticles is highly dependent on their size and surface, the complete and adequate characterization of the nanoparticle is important. This review discusses the characterization and antimicrobial activity of biogenic synthesized silver nanoparticles and silver chloride nanoparticles. By revising the literature, there is confusion in the characterization of these two silver-based nanoparticles, which consequently affects the conclusion regarding to their antimicrobial activities. This review critically analyzes recent publications on the synthesis of biogenic silver nanoparticles and silver chloride nanoparticles by attempting to correlate the characterization of the nanoparticles with their antimicrobial activity. It was difficult to correlate the size of biogenic nanoparticles with their antimicrobial activity, since different techniques are employed for the characterization. Biogenic synthesized silver-based nanoparticles are not completely characterized, particularly the nature of capped proteins covering the nanomaterials. Moreover, the antimicrobial activity of theses nanoparticles is assayed by using different protocols and strains, which difficult the comparison among the published papers. It is important to select some bacteria as standards, by following international foundations (Pharmaceutical Microbiology Manual) and use the minimal inhibitory concentration by broth microdilution assays from Clinical and Laboratory Standards Institute, which is the most common assay used in antibiotic ones. Therefore, we conclude that to have relevant results on antimicrobial effects of biogenic silver-based nanoparticles, it is necessary to have a complete and adequate characterization of these nanostructures, followed by standard methodology in microbiology protocols.

  7. 3, 4-dihydroxy-L-phenylalanine-derived melanin from Yarrowia lipolytica mediates the synthesis of silver and gold nanostructures.

    Science.gov (United States)

    Apte, Mugdha; Girme, Gauri; Bankar, Ashok; Ravikumar, Ameeta; Zinjarde, Smita

    2013-01-30

    Nanobiotechnology applies the capabilities of biological systems in generating a variety of nano-sized structures. Plants, algae, fungi and bacteria are some systems mediating such reactions. In fungi, the synthesis of melanin is an important strategy for cell-survival under metal-stressed conditions. Yarrowia lipolytica, the biotechnologically significant yeast also produces melanin that sequesters heavy metal ions. The content of this cell-associated melanin is often low and precursors such as L-tyrosine or 3, 4-dihydroxy-L-phenylalanine (L-DOPA) can enhance its production. The induced melanin has not been exploited for the synthesis of nanostructures. In this investigation, we have employed L-DOPA-melanin for the facile synthesis of silver and gold nanostructures. The former have been used for the development of anti-fungal paints. Yarrowia lipolytica NCIM 3590 cells were incubated with L-DOPA for 18 h and the resultant dark pigment was subjected to physical and chemical analysis. This biopolymer was used as a reducing and stabilizing agent for the synthesis of silver and gold nanostructures. These nanoparticles were characterized by UV-Visible spectra, X-ray diffraction (XRD) studies, and electron microscopy. Silver nanoparticles were evaluated for anti-fungal activity. The pigment isolated from Y. lipolytica was identified as melanin. The induced pigment reduced silver nitrate and chloroauric acid to silver and gold nanostructures, respectively. The silver nanoparticles were smaller in size (7 nm) and displayed excellent anti-fungal properties towards an Aspergillus sp. isolated from a wall surface. An application of these nanoparticles as effective paint-additives has been demonstrated. The yeast mediated enhanced production of the metal-ion-reducing pigment, melanin. A simple and rapid method for the extracellular synthesis of nanoparticles with paint-additive-application was developed.

  8. Lithium Promotes Neuronal Repair and Ameliorates Depression-Like Behavior following Trimethyltin-Induced Neuronal Loss in the Dentate Gyrus

    Science.gov (United States)

    Yoneyama, Masanori; Shiba, Tatsuo; Hasebe, Shigeru; Umeda, Kasumi; Yamaguchi, Taro; Ogita, Kiyokazu

    2014-01-01

    Lithium, a mood stabilizer, is known to ameliorate the stress-induced decrease in hippocampal neurogenesis seen in animal models of stress-related disorders. However, it is unclear whether lithium has beneficial effect on neuronal repair following neuronal damage in neuronal degenerative diseases. Here, we evaluated the effect of in vivo treatment with lithium on the hippocampal neuronal repair in a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampal dentate gyrus (such mice referred to as “impaired animals”) [Ogita et al. (2005) J Neurosci Res 82: 609–621]. The impaired animals had a dramatically increased number of 5-bromo-2′-deoxyuridine (BrdU)-incorporating cells in their dentate gyrus at the initial time window (days 3 to 5 post-TMT treatment) of the self-repair stage. A single treatment with lithium produced no significant change in the number of BrdU-incorporating cells in the dentate granule cell layer and subgranular zone on day 3 post-TMT treatment. On day 5 post-TMT treatment, however, BrdU-incorporating cells were significantly increased in number by lithium treatment for 3 days. Most interestingly, chronic treatment (15 days) with lithium increased the number of BrdU-incorporating cells positive for NeuN or doublecortin in the dentate granule cell layer of the impaired animals, but not in that of naïve animals. The results of a forced swimming test revealed that the chronic treatment with lithium improved the depression-like behavior seen in the impaired animals. Taken together, our data suggest that lithium had a beneficial effect on neuronal repair following neuronal loss in the dentate gyrus through promoted proliferation and survival/neuronal differentiation of neural stem/progenitor cells in the subgranular zone. PMID:24504050

  9. CHIP Is an Essential Determinant of Neuronal Mitochondrial Stress Signaling

    Science.gov (United States)

    Palubinsky, Amy M.; Stankowski, Jeannette N.; Kale, Alixandra C.; Codreanu, Simona G.; Singer, Robert J.; Liebler, Daniel C.; Stanwood, Gregg D.

    2015-01-01

    Abstract Aims: Determine the mechanism by which C-terminus of HSC70-interacting protein (CHIP) induction alters neuronal survival under conditions of mitochondrial stress induced by oxygen glucose deprivation. Results: We report that animals deficient in the E3 ubiquitin ligase, CHIP, have high baseline levels of central nervous system protein oxidation and lipid peroxidation, reduced antioxidant defenses, and decreased energetic status. Stress-associated molecules typically linked to Parkinson's disease such as the mitochondrial kinase, PTEN-inducible putative kinase 1 (PINK1), and another E3 ligase, Parkin, are upregulated in brains from CHIP knockout (KO) animals. Utilizing a novel biotin–avidin capture technique, we found that the oxidation status of Parkin and the mitochondrial fission protein, dynamin-related protein 1 (Drp1), are altered in a CHIP-dependent manner. We also found that following oxygen–glucose deprivation (OGD), the expression of CHIP, PINK1, and the autophagic marker, LC3, increase and there is activation of the redox-sensitive kinase p66shc. Under conditions of OGD, CHIP relocalizes from the cytosol to mitochondria. Mitochondria from CHIP KO mice have profound impairments in stress response induced by calcium overload, resulting in accelerated permeability transition activity. While CHIP-deficient neurons are morphologically intact, they are more susceptible to OGD consistent with a previously unknown neuroprotective role for CHIP in maintaining mitochondrial homeostasis. Innovation: CHIP relocalization to the mitochondria is essential for the regulation of mitochondrial integrity and neuronal survival following OGD. Conclusions: CHIP is an essential regulator of neuronal bioenergetics and redox tone. Altering the expression of this protein has profound effects on neuronal survival when cells are exposed to OGD. Antioxid. Redox Signal. 23, 535–549. PMID:25602369

  10. Protection of dopaminergic neurons in primary culture by lisuride.

    Science.gov (United States)

    Gille, G; Rausch, W D; Hung, S T; Moldzio, R; Ngyuen, A; Janetzky, B; Engfer, A; Reichmann, H

    2002-02-01

    Dopamine agonists play an important role in the treatment of Parkinson's disease by reducing the administration of L-3,4-dihydroxyphenylalanine (L-DOPA). The enzymatic and non-enzymatic conversion of L-DOPA is suspected to increase oxidative stress, which leads to the degeneration of dopaminergic neurons in Parkinson's disease. In primary mouse mesencephalic cultures we show that the dopamine D1/D2 receptor agonist lisuride, in a concentration range of 0.001-1 microM, enhances the survival of dopaminergic neurons, protects against toxicity induced by L-DOPA or 1-methyl-4-phenylpyridinium ion (MPP+) and stimulates 3H-dopamine uptake. Lisuride also reduces anaerobic metabolism during incubation with L-DOPA. The present findings suggest that lisuride may have trophic/survival-promoting properties and potentially reduces oxidative stress.

  11. Green synthesis of colloid silver nanoparticles and resulting biodegradable starch/silver nanocomposites.

    Science.gov (United States)

    Cheviron, Perrine; Gouanvé, Fabrice; Espuche, Eliane

    2014-08-08

    Environmentally friendly silver nanocomposite films were prepared by an ex situ method consisting firstly in the preparation of colloidal silver dispersions and secondly in the dispersion of the as-prepared nanoparticles in a potato starch/glycerol matrix, keeping a green chemistry process all along the synthesis steps. In the first step concerned with the preparation of the colloidal silver dispersions, water, glucose and soluble starch were used as solvent, reducing agent and stabilizing agent, respectively. The influences of the glucose amount and reaction time were investigated on the size and size distribution of the silver nanoparticles. Two distinct silver nanoparticle populations in size (diameter around 5 nm size for the first one and from 20 to 50 nm for the second one) were distinguished and still highlighted in the potato starch/glycerol based nanocomposite films. It was remarkable that lower nanoparticle mean sizes were evidenced by both TEM and UV-vis analyses in the nanocomposites in comparison to the respective colloidal silver dispersions. A dispersion mechanism based on the potential interactions developed between the nanoparticles and the polymer matrix and on the polymer chain lengths was proposed to explain this morphology. These nanocomposite film series can be viewed as a promising candidate for many applications in antimicrobial packaging, biomedicines and sensors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Silver nanoparticles decorated lipase-sensitive polyurethane micelles for on-demand release of silver nanoparticles.

    Science.gov (United States)

    Su, Yuling; Zhao, Lili; Meng, Fancui; Wang, Quanxin; Yao, Yongchao; Luo, Jianbin

    2017-04-01

    In order to improve the antibacterial activities while decrease the cytotoxity of silver nanoparticles, we prepared a novel nanocomposites composed of silver nanoparticles decorated lipase-sensitive polyurethane micelles (PUM-Ag) with MPEG brush on the surface. The nanocomposite was characterized by UV-vis, TEM and DLS. UV-vis and TEM demonstrated the formation of silver nanoparticles on PU micelles and the nanoassembly remained intact without the presence of lipase. The silver nanoparticles were protected by the polymer matrix and PEG brush which show good cytocompatibility to HUVEC cells and low hemolysis. Moreover, at the presence of lipase, the polymer matrix of nanocomposites is subject to degradation and the small silver nanoparticles were released as is shown by DLS and TEM. The MIC and MBC studies showed an enhanced toxicity of the nanocomposites to both gram negative and gram positive bacteria, i.e. E. coli and S. aureus, as the result of the degradation of polymer matrix by bacterial lipase. Therefore, the nanocomposites are biocompatible to mammalian cells cells which can also lead to activated smaller silver nanoparticles release at the presence of bacteria and subsequently enhanced inhibition of bacteria growth. The satisfactory selectivity for bacteria compared to HUVEC and RBCs make PUM-Ag a promising antibacterial nanomedicine in biomedical field. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Resonate-and-fire neurons.

    Science.gov (United States)

    Izhikevich, E M

    2001-01-01

    We suggest a simple spiking model-resonate-and-fire neuron, which is similar to the integrate-and-fire neuron except that the state variable is complex. The model provides geometric illustrations to many interesting phenomena occurring in biological neurons having subthreshold damped oscillations of membrane potential. For example, such neurons prefer a certain resonant frequency of the input that is nearly equal to their eigenfrequency, they can be excited or inhibited by a doublet (two pulses) depending on its interspike interval, and they can fire in response to an inhibitory input. All these properties could be observed in Hodgkin-Huxley-type models. We use the resonate-and-fire model to illustrate possible sensitivity of biological neurons to the fine temporal structure of the input spike train. Being an analogue of the integrate-and-fire model, the resonate-and-fire model is computationally efficient and suitable for simulations of large networks of spiking neurons.

  14. Unique aspects of transcriptional regulation in neurons – nuances in NFκB and Sp1-related factors

    Directory of Open Access Journals (Sweden)

    Chen Yuzhi

    2009-05-01

    Full Text Available Abstract The unique physiology and function of neurons create differences in their cellular physiology, including their regulation of gene expression. We began several years ago exploring the relationships between the NFκB transcription factor, neuronal survival, and glutamate receptor activation in telencephalic neurons. These studies led us to conclude that this population of cells is nearly incapable of activating the NFκB that is nonetheless expressed at reasonable levels. A subset of the κB cis elements are instead bound by members of the Sp1 family in neurons. Also surprising was our discovery that Sp1 itself, typically described as ubiquitous, is severely restricted in expression within forebrain neurons; Sp4 seems to be substituted during neuronal differentiation. These findings and their implications for neuronal differentiation – as well as potential dedifferentiation during degenerative processes – are discussed here.

  15. Biosynthesis and structural characterization of silver nanoparticles from bacterial isolates

    Energy Technology Data Exchange (ETDEWEB)

    Zaki, Sahar, E-mail: saharzaki@yahoo.com [Environmental Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, Mubarak City for Scientific Research and Technology Applications, Alexandria, 21934 New Burgelarab City (Egypt); El Kady, M.F. [Fabrication Technology Department, Advanced Technology and New Materials Research Institute (ATNMRI), Mubarak City for Scientific Research and Technology Applications, Alexandria (Egypt); Abd-El-Haleem, Desouky [Environmental Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, Mubarak City for Scientific Research and Technology Applications, Alexandria, 21934 New Burgelarab City (Egypt)

    2011-10-15

    Graphical abstract: In this study five bacterial isolates belong to different genera were found to be able to biosynthesize silver nanoparticles. Biosynthesis and spectral characterization are reported here. Highlights: {yields} About 300 bacterial isolates were screened for their ability to produce nanosilvers {yields} Five of them were potential candidates for synthesis of silver nanoparticles {yields} Production of silver nanoparticles was examined using UV-Vis, XRD, SEM and EDS. {yields} The presence of nanoparticles with all five bacterial isolates was confirmed. -- Abstract: This study aimed to develop a green process for biosynthesis of silver nanomaterials by some Egyptian bacterial isolates. This target was achieved by screening an in-house culture collection consists of 300 bacterial isolates for silver nanoparticle formation. Through screening process, it was observed that strains belonging to Escherichia coli (S30, S78), Bacillus megaterium (S52), Acinetobacter sp. (S7) and Stenotrophomonas maltophilia (S54) were potential candidates for synthesis of silver nanoparticles. The extracellular production of silver nanoparticles by positive isolates was investigated by UV-Vis spectroscopy, X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The results demonstrated that UV-visible spectrum of the aqueous medium containing silver ion showed a peak at 420 nm corresponding to the plasmon absorbance of silver nanoparticles. Scanning electron microscopy micrograph showed formation of silver nanoparticles in the range of 15-50 nm. XRD-spectrum of the silver nanoparticles exhibited 2{theta} values corresponding to the silver nanocrystal that produce in hexagonal and cubic crystal configurations with different plane of orientation. In addition, the signals of the silver atoms were observed by EDS-spectrum analysis that confirms the presence of silver nanoparticles (Ag

  16. Colloidal silver solutions with antimicrobial properties

    Energy Technology Data Exchange (ETDEWEB)

    Petica, A. [INCDIE ICPE-Advanced Research, Bucharest (Romania)], E-mail: petica@icpe-ca.ro; Gavriliu, S.; Lungu, M.; Buruntea, N. [INCDIE ICPE-Advanced Research, Bucharest (Romania); Panzaru, C. [Institute of Medicine and Pharmacy, Iassy (Romania)

    2008-08-25

    Some colloidal silver solutions involving the electrochemical technique with 'sacrificial anode method and different stabilizers and co-stabilizers' have been prepared. A constant current pulse generator with stirrer at different working times has been used. To achieve stable colloidal silver solutions, a mix of different tensioactive agents namely [poly (N-vinylpyrrolidone)], Na-naphthalene sulphonate, Na-lauryl sulfate and Na-dodecyl sulphonate were tested. The effects of these various mixes of polymer and ionic surfactants upon the Ag concentration and UV-vis spectra of silver nanoparticles were determined by spectrophotometer techniques. The nanoparticles sizes have been analyzed through dynamic light scattering technique and the silver nanoparticle morphology has been evidenced by transmission electron microscopy (TEM). Micobiological analysis has been made by determining minimal inhibitorial concentration upon the following germs: Staphylococcus aureus (ATCC) (Gram-positive cocci), Pseudomonas aeruginosa (ATTC), Escherichia coli (ATCC) and Acinetobacter spp. (Gram-negative coccobacillus). To evaluate the antifungal effect, the antibiogram method involving various tests using a fungi mix of Aspergillus, Penicillium and Trichoderma species has been used. The presented method allows obtaining of some stable colloidal solutions containing up to 35 ppm of Ag with very good antimicrobial and antifungal properties.

  17. Microwave assisted template synthesis of silver nanoparticles

    Indian Academy of Sciences (India)

    Easier, less time consuming, green processes, which yield silver nanoparticles of uniform size, shape and morphology are of interest. Various methods for synthesis, such as conventional temperature assisted process, controlled reaction at elevated temperatures, and microwave assisted process have been evaluated for ...

  18. Reinforcement of Conducting Silver-based Materials

    Directory of Open Access Journals (Sweden)

    Heike JUNG

    2014-09-01

    Full Text Available Silver is a well-known material in the field of contact materials because of its high electrical and thermal conductivity. However, due to its bad mechanical and switching properties, silver alloys or reinforcements of the ductile silver matrix are required. Different reinforcements, e. g. tungsten, tungsten carbide, nickel, cadmium oxide or tin oxide, are used in different sectors of switches. To reach an optimal distribution of these reinforcements, various manufacturing techniques (e. g. powder blending, preform infiltration, wet-chemical methods, internal oxidation are being used for the production of these contact materials. Each of these manufacturing routes offers different advantages and disadvantages. The mechanical alloying process displays a successful and efficient method to produce particle-reinforced metal-matrix composite powders. This contribution presents the obtained fine disperse microstructure of tungsten-particle-reinforced silver composite powders produced by the mechanical alloying process and displays this technique as possible route to provide feedstock powders for subsequent consolidation processes. DOI: http://dx.doi.org/10.5755/j01.ms.20.3.4889

  19. Characterization of Fe -doped silver phosphate glasses

    Indian Academy of Sciences (India)

    tures of the glass and at lower concentration of dopant, a nanostructure is obtained. Electrical conductivity mea- surements from 303 to 373 K in a frequency range from 100 Hz to 5 MHz have indicated that all glasses are ionic conductors with Ag+ ions as the charge carrier. Fe2O3 doping in silver phosphate glass increased ...

  20. Biosynthesis of silver nanoparticles synthesized by Aspergillus ...

    Indian Academy of Sciences (India)

    agents. Keywords. Aspergillus flavus; silver nanoparticles; antimicrobial; antioxidant; cytotoxicity. 1. Introduction. Nanoparticles with controlled size and composition are of fundamental and technological interest as they provide solu- tions to technological and environmental challenges in the areas of solar energy conversion ...