Barski, Elisabeth

[["dc.bibliographiccitation.firstpage","3472"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","FEBS Journal"],["dc.bibliographiccitation.lastpage","3483"],["dc.bibliographiccitation.volume","278"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Barski, E."],["dc.contributor.author","Lingor, P."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Michel, U."],["dc.date.accessioned","2017-09-07T11:43:25Z"],["dc.date.available","2017-09-07T11:43:25Z"],["dc.date.issued","2011"],["dc.description.abstract","Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor of neuron-specific genes that binds to a conserved DNA element, the neuron restrictive silencer element (NRSE/RE1). Interestingly, increased REST activity is found in several neurological diseases like Huntington's disease and cerebral ischemia. Recently, it was shown that NRSE dsRNA, a double-stranded non-coding RNA can bind to REST during a defined period of neuronal differentiation, and thereby changes REST from a transcriptional repressor to an activator of neuron-specific genes. Here, we analyzed the effects of NRSE dsRNA expression in primary retinal ganglion cells. We found that NRSE dsRNA expression vectors significantly enhance neurite outgrowth even when axonal degeneration is induced by neurotrophin deprivation. Transfection of HEK cells with NRSE dsRNA-expressing vectors altered their morphology leading to the formation of thin processes and induced the expression of neurofilament-68. Surprisingly, control vectors containing REST-binding sites, but not expressing NRSE dsRNA, resulted in the same effects, also in the retinal ganglion cell model. Reporter assays and retention of REST in the cytoplasm with a labeled NRSE/RE1-containing plasmid incapable of entering the nucleus suggest that sequestration of REST in the cytoplasm is the reason for the observed effects. No evidence for a biological function of NRSE dsRNA could be found in these models. We conclude that sequestration of REST leads to enhanced neurite outgrowth in retinal ganglion cells and that an increased activity of REST, as it is found in several neurodegenerative diseases, can be effectively modulated by sequestration of REST with plasmids containing NRSE/RE1 sites."],["dc.identifier.doi","10.1111/j.1742-4658.2011.08269.x"],["dc.identifier.gro","3142674"],["dc.identifier.isi","000294810600024"],["dc.identifier.pmid","21790997"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/104"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1742-464X"],["dc.title","Plasmids containing NRSE/RE1 sites enhance neurite outgrowth of retinal ganglion cells via sequestration of REST independent of NRSE dsRNA expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","250"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","263"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Tönges, Lars"],["dc.contributor.author","Pieper, Nicole"],["dc.contributor.author","Bermel, Christina"],["dc.contributor.author","Barski, Elisabeth"],["dc.contributor.author","Planchamp, Veronique"],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2017-09-07T11:48:48Z"],["dc.date.available","2017-09-07T11:48:48Z"],["dc.date.issued","2008"],["dc.description.abstract","Functional regeneration in the CNS is limited by lesion-induced neuronal apoptosis and an environment inhibiting axonal elongation. A principal, yet unresolved question is the interaction between these two major factors. We thus evaluated the role of pharmacological inhibition of rho kinase (ROCK), a key mediator of myelin-derived axonal growth inhibition and CNTF, a potent neurotrophic factor for retinal ganglion cells (RGC), in models of retinal ganglion cell apoptosis and neurite outgrowth/regeneration in vitro and in vivo. Here, we show for the first time that the ROCK inhibitor Y-27632 significantly enhanced survival of RGC in vitro and in vivo. In vitro, the co-application of CNTF and Y-27632 potentiated the effect of either substance alone. ROCK inhibition resulted in the activation of the intrinsic MAPK pathway, and the combination of CNTF and Y-27632 resulted in even more pronounced MAPK activation. While CNTF also induced STAT3 phosphorylation, the additional application of ROCK inhibitor surprisingly diminished the effects of CNTF on STAT3 phosphorylation. ROCK activity was also decreased in an additive manner by both substances. In vivo, both CNTF and Y-27632 enhanced regeneration of RGC into the non-permissive optic nerve crush model and additive effects were observed after combination treatment. Further evaluation using specific inhibitors delineate STAT3 as a negative regulator of neurite growth and positive regulator of cell survival, while MAPK and Akt support neurite growth. These results show that next to neurotrophic factors ROCK inhibition by Y-27632 potently supports survival of lesioned adult CNS neurons. Co-administration of CNTF and Y-27632 results in additive effects on neurite outgrowth and regeneration. The interaction of intracellular signalling pathways may, however, attenuate more pronounced synergy and has to be taken into account for future treatment strategies."],["dc.identifier.doi","10.1093/brain/awm284"],["dc.identifier.gro","3143369"],["dc.identifier.isi","000251865700021"],["dc.identifier.pmid","18063589"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/875"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0006-8950"],["dc.subject","retinal ganglion cells; CNTF; rho kinase; axotomy; regeneration"],["dc.title","ROCK inhibition and CNTF interact on intrinsic signalling pathways and differentially regulate survival and regeneration in retinal ganglion cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","217"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","232"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Günther, R."],["dc.contributor.author","Suhr, M."],["dc.contributor.author","Jansen, J."],["dc.contributor.author","Balck, A."],["dc.contributor.author","Saal, K.-A."],["dc.contributor.author","Barski, E."],["dc.contributor.author","Nientied, T."],["dc.contributor.author","Götz, A. A."],["dc.contributor.author","Koch, J.-C."],["dc.contributor.author","Mueller, B. K."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Sereda, M. W."],["dc.contributor.author","Hanisch, U.-K."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:53Z"],["dc.date.available","2017-09-07T11:46:53Z"],["dc.date.issued","2014"],["dc.description.abstract","Disease progression in amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons (MN) and their axons, but is also influenced by neighboring cells such as astrocytes and microglial cells. The role of microglia in ALS is complex as it switches from an anti-inflammatory and neuroprotective phenotype in early disease to a proinflammatory and neurotoxic phenotype in later stages. Our previous studies in models of neurodegeneration identified rho kinase (ROCK) as a target, which can be manipulated to beneficially influence disease progression. Here, we examined the neuroprotective potential of the ROCK inhibitor Fasudil to target the central pathogenic features of ALS. Application of Fasudil to kainic acid-lesioned primary MN in vitro resulted in a strong prosurvival effect. In vivo, SOD1(G93A) mice benefited from oral treatment with Fasudil showing prolonged survival and improved motor function. These findings were correlated to an improved survival of motor neurons and a pronounced alteration of astroglial and microglial cell infiltration of the spinal cord under Fasudil treatment. Modeling a proinflammatory microglial phenotype by stimulation with LPS in vitro, Fasudil decreased the release of proinflammatory cytokines and chemokines TNF, Il6, CCL2, CCL3, and CCL5 while CXCL1 release was only transiently suppressed. In sciatic nerve motor axons, neuromuscular junction remodeling processes were increased. In conclusion, we provide preclinical and neurobiological evidence that inhibition of ROCK by the clinically approved small molecule inhibitor Fasudil may be a novel therapeutic approach in ALS combining both neuroprotection and immunomodulation for the cure of this devastating disease. GLIA 2014;62:217-232"],["dc.identifier.doi","10.1002/glia.22601"],["dc.identifier.gro","3142195"],["dc.identifier.isi","000328209300005"],["dc.identifier.pmid","24311453"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5588"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Rho Kinase Inhibition Modulates Microglia Activation and Improves Survival in a Model of Amyotrophic Lateral Sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1225"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Barski, E."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:15Z"],["dc.date.available","2017-09-07T11:46:15Z"],["dc.date.issued","2014"],["dc.description.abstract","The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.format.extent","12"],["dc.identifier.doi","10.1038/cddis.2014.191"],["dc.identifier.gro","3142130"],["dc.identifier.isi","000337229300025"],["dc.identifier.pmid","24832597"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4877"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","2041-4889"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject","Cell death in the nervous system; Cell signalling; Neurodegeneration; Regeneration and repair in the nervous system"],["dc.title","ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","309"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.journal","NeuroMolecular Medicine"],["dc.bibliographiccitation.lastpage","321"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Carboni, Eleonora"],["dc.contributor.author","Tatenhorst, Lars"],["dc.contributor.author","Tönges, Lars"],["dc.contributor.author","Barski, Elisabeth"],["dc.contributor.author","Dambeck, Vivian"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2018-04-23T11:49:32Z"],["dc.date.available","2018-04-23T11:49:32Z"],["dc.date.issued","2017"],["dc.description.abstract","Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD brains during disease progression. In our study, we focused on the interaction of Fe and aggregating aSyn in vivo in a transgenic mouse model overexpressing human aSyn bearing the A53T mutation (prnp.aSyn.A53T). We utilized a neonatal iron-feeding model to exacerbate the motor phenotype of the transgenic mouse model. Beginning from day 100, mice were treated with deferiprone (DFP), a ferric chelator that is able to cross the blood–brain barrier and is currently used in clinics as treatment for hemosiderosis. Our paradigm resulted in an impairment of the learning abilities in the rotarod task and the novel object recognition test. DFP treatment significantly improved the performance in both tasks. Although this was not accompanied by alterations in aSyn aggregation, our results support DFP as possible therapeutic option in PD."],["dc.identifier.doi","10.1007/s12017-017-8447-9"],["dc.identifier.gro","3142070"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13724"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","1535-1084"],["dc.title","Deferiprone Rescues Behavioral Deficits Induced by Mild Iron Exposure in a Mouse Model of Alpha-Synuclein Aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1769"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","ACS Chemical Neuroscience"],["dc.bibliographiccitation.lastpage","1779"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Dučić, Tanja"],["dc.contributor.author","Carboni, Eleonora"],["dc.contributor.author","Lai, Barry"],["dc.contributor.author","Chen, Si"],["dc.contributor.author","Michalke, Bernhard"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Barski, Elisabeth"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2017-09-07T11:43:30Z"],["dc.date.available","2017-09-07T11:43:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Manganese (Mn) may foster aggregation of alpha-synuclein (alpha Syn) contributing to the pathogenesis of PD. Here, we examined the influence of aSyn overexpression on distribution and oxidation states of Mn in frozen-hydrated primary midbrain neurons (PMNs) by synchrotron-based Xray fluorescence (XRF) and X-ray absorption near edge structure spectroscopy (XANES). Overexpression of aSyn increased intracellular Mn levels, whereas levels of Ca, Zn, K, P, and S were significantly decreased. Mn oxidation states were not altered. A strong correlation between Cu-/Mn-levels as well as Fe-/Mn-levels was observed in alpha Syn-overexpressing cells. Subcellular resolution revealed a punctate or filament-like perinuclear and neuritic distribution of Mn, which resembled the expression of DMT1 and MnSOD. While overexpression of aSyn did not significantly alter the expression patterns of the most-expressed Mn transport proteins (DMT1, VGCC, Fpn1), it attenuated the Mn release from Mn-treated neurons. Thus, these data suggest that aSyn may act as an intracellular Mn store. In total, neurotoxicity in PD could be mediated via regulation of transition metal levels and the metal-binding capacity of aSyn, which could represent a promising therapeutic target for this neurodegenerative disorder."],["dc.identifier.doi","10.1021/acschemneuro.5b00093"],["dc.identifier.gro","3141816"],["dc.identifier.isi","000363435300012"],["dc.identifier.pmid","26284970"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1390"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1948-7193"],["dc.title","Alpha-Synuclein Regulates Neuronal Levels of Manganese and Calcium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2810"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","2827"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Vahsen, Björn Friedhelm"],["dc.contributor.author","Ribas, Vinicius Toledo"],["dc.contributor.author","Sundermeyer, Jonas"],["dc.contributor.author","Boecker, Alexander"],["dc.contributor.author","Dambeck, Vivian"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Caldi Gomes, Lucas"],["dc.contributor.author","Tatenhorst, Lars"],["dc.contributor.author","Barski, Elisabeth"],["dc.contributor.author","Roser, Anna-Elisa"],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Koch, Jan Christoph"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2020-12-10T18:09:42Z"],["dc.date.available","2020-12-10T18:09:42Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41418-020-0543-y"],["dc.identifier.eissn","1476-5403"],["dc.identifier.issn","1350-9047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73733"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","250"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","261"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Dučić, Tanja"],["dc.contributor.author","Barski, Elisabeth"],["dc.contributor.author","Salome, Murielle"],["dc.contributor.author","Koch, Jan C."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2017-09-07T11:48:19Z"],["dc.date.available","2017-09-07T11:48:19Z"],["dc.date.issued","2013"],["dc.description.abstract","Transition metals have been suggested to play a pivotal role in the pathogenesis of Parkinson's disease. X-ray microscopy combined with a cryogenic setup is a powerful method for elemental imaging in low concentrations and high resolution in intact cells, eliminating the need for fixation and sectioning of the specimen. Here, we performed an elemental distribution analysis in cultured primary midbrain neurons with a step size in the order of 300 nm and 0.1 ppm sensitivity under cryo conditions by using X-ray fluorescence microscopy. We report the elemental mappings on the subcellular level in primary mouse dopaminergic (DAergic) and non-DAergic neurons after treatment with transition metals. Application of Fe2+ resulted in largely extracellular accumulation of iron without preference for the neuronal transmitter subtype. A quantification of different Fe oxidation states was performed using X-ray absorption near edge structure analysis. After treatment with Mn2+, a cytoplasmic/paranuclear localization of Mn was observed preferentially in DAergic neurons, while no prominent signal was detectable after Mn3+ treatment. Immunocytochemical analysis correlated the preferential Mn uptake to increased expression of voltage-gated calcium channels in DAergic neurons. We discuss the implications of this differential elemental distribution for the selective vulnerability of DAergic neurons and Parkinson's disease pathogenesis."],["dc.identifier.doi","10.1111/jnc.12073"],["dc.identifier.gro","3142417"],["dc.identifier.isi","000313260200010"],["dc.identifier.pmid","23106162"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8509"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8052"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","Im Artikel selbst steht kein Hinweis auf eine cc Lizenz. Bei Wiley sind aber die Artikel, die mit einem lila Schloss-Symbol gekennzeichnet sind, open access und dürfen archiviert werden."],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0022-3042"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","X-ray fluorescence analysis of iron and manganese distribution in primary dopaminergic neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]