Bermel, Christina

[["dc.bibliographiccitation.firstpage","2606"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2619"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Planchamp, V."],["dc.contributor.author","Bermel, C."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Ostendorf, T."],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Reed, J. C."],["dc.contributor.author","Kermer, Pawel"],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:48:10Z"],["dc.date.available","2017-09-07T11:48:10Z"],["dc.date.issued","2008"],["dc.description.abstract","Improved survival of injured neurons and the inhibition of repulsive environmental signalling are prerequisites for functional regeneration. BAG1 (Bcl-2-associated athanogene-1) is an Hsp70/Hsc70-binding protein, which has been shown to suppress apoptosis and enhance neuronal differentiation. We investigated BAG1 as a therapeutic molecule in the lesioned visual system in vivo. Using an adeno-associated viral vector, BAG1 (AAV.BAG1) was expressed in retinal ganglion cells (RGC) and then tested in models of optic nerve axotomy and optic nerve crush. BAG1 significantly increased RGC survival as compared to adeno-associated viral vector enhanced green fluorescent protein (AAV.EGFP) treated controls and this was independently confirmed in transgenic mice over-expressing BAG1 in neurons. The numbers and lengths of regenerating axons after optic nerve crush were also significantly increased in the AAV.BAG1 group. In pRGC cultures, BAG1-over-expression resulted in a similar to 3-fold increase in neurite length and growth cone surface. Interestingly, BAG1 induced an intracellular translocation of Raf-1 and ROCK2 and ROCK activity was decreased in a Raf-1-dependent manner by BAG1-over-expression. In summary, we show that BAG1 acts in a dual role by inhibition of lesion-induced apoptosis and interaction with the inhibitory ROCK signalling cascade. BAG1 is therefore a promising molecule to be further examined as a putative therapeutic tool in neurorestorative strategies."],["dc.identifier.doi","10.1093/brain/awn196"],["dc.identifier.gro","3143228"],["dc.identifier.isi","000260381300008"],["dc.identifier.pmid","18757464"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/719"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0006-8950"],["dc.subject","BAG1; ROCK2; Raf-1 kinase; retinal ganglion cell; regeneration; apoptosis"],["dc.title","BAG1 promotes axonal outgrowth and regeneration in vivo via Raf-1 and reduction of ROCK activity"],["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","427"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Molecular and Cellular Neuroscience"],["dc.bibliographiccitation.lastpage","437"],["dc.bibliographiccitation.volume","42"],["dc.contributor.author","Bermel, C."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Planchamp, V."],["dc.contributor.author","Gillardon, F."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Dietz, G. P. H."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:47Z"],["dc.date.available","2017-09-07T11:46:47Z"],["dc.date.issued","2009"],["dc.description.abstract","CNS regeneration is limited by lesion-induced neuronal apoptosis and an environment inhibiting axonal elongation. Inhibition of ROCK has been previously shown to promote regeneration in retinal ganglion cells (RGC) whereas Cdk5 inhibition mainly promoted survival. Therefore, we have evaluated the effects of combined treatment with inhibitors of ROCK and Cdk5. We show that in vitro, the co-application of the Cdk5 inhibitor, Indolinone A, and the ROCK inhibitor, Y-27632, potentiated the survival-promoting effect of either substance alone. However, neurite outgrowth in vitro was promoted only by the presence of Y-27632, not by Indolinone A alone. In the ex vivo explant and the in vivo optic nerve crush model the combination of both inhibitors significantly increased neurite outgrowth at small distances, but this effect leveled off for longer neurites. In Summary, the combined treatment with the Cdk5 inhibitor Indolinone A and the ROCK inhibitor Y-27632 results in a strong additive effect on neuronal survival, but is not able to increase the regenerative response beyond the effect of the ROCK inhibitor. (C) 2009 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.mcn.2009.09.005"],["dc.identifier.gro","3143032"],["dc.identifier.isi","000272121000017"],["dc.identifier.pmid","19782753"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/501"],["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","1044-7431"],["dc.title","Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]