Rohde, Gundula

[["dc.bibliographiccitation.firstpage","1514"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Investigative Ophthalmology & Visual Science"],["dc.bibliographiccitation.lastpage","1522"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Rohde, Gundula"],["dc.contributor.author","Pölking, Esther"],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2017-09-07T11:43:24Z"],["dc.date.available","2017-09-07T11:43:24Z"],["dc.date.issued","2004"],["dc.description.abstract","Purpose. Erythropoietin (EPO) modulates erythropoiesis by inhibiting apoptosis in erythrocyte progenitors. Recently, EPO has been shown to be protective in experimental models of mechanical trauma, neuroinflammation, cerebral and retinal ischemia, and even in a human stroke trial. However, little is known about EPO signal transduction in vivo and the usefulness of EPO in the prevention of the chronic, purely apoptotic neuronal cell death that contributes to vision loss in glaucoma and the progression of neurodegenerative diseases. Methods. EPO's effects and signaling in the retinal ganglion cell axotomy paradigm were studied by Western blot analysis and immunohistochemistry, receptor expression was characterized in the retina before and after lesion. EPO was injected into the vitreous body to investigate neuroprotection of axotomized rat RGCs. Moreover, EPO's effects were studied in cultures of immunopurified retinal ganglion cells. Signal-transduction pathways transmitting neuroprotective EPO effects in vivo were characterized by the use of specific kinase inhibitors, immunohistochemistry, and Western blot analysis. Results. EPO receptors (EPORs) were expressed on RGC somata and dendrites in vivo. EPOR expression did not significantly change after axotomy. Application of EPO prevented death of neurotrophic-factor-deprived immunopurified rat RGCs in vitro, rescued axotomized RGCs in vivo, and prevented caspase-3 activation. EPO-induced Akt phosphorylation and survival-promoting EPO effects were completely abolished by inhibition of PI-3-kinase. EPO neuroprotection followed a bell-shaped dose-response curve in vitro and in vivo, whereas toxic EPO effects were never observed, even at high concentrations. Conclusions. These data support a potential role for EPO as a therapeutic molecule against predominantly apoptotic neuronal cell death in the context of glaucoma or neurodegenerative diseases and delineate the PI-3-K/Akt pathway as the predominant mediator of EPO neuroprotection in this in vivo paradigm of neuronal cell death."],["dc.identifier.doi","10.1167/iovs.03-1039"],["dc.identifier.gro","3143992"],["dc.identifier.isi","000221084700034"],["dc.identifier.pmid","15111610"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1566"],["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","0146-0404"],["dc.title","Effect of Erythropoietin Axotomy-Induced Apoptosis in Rat 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","359"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuroscience"],["dc.bibliographiccitation.lastpage","364"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Kilic, E."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Kilic, Ü."],["dc.contributor.author","Rohde, G."],["dc.contributor.author","Yulug, B."],["dc.contributor.author","Peters, K."],["dc.contributor.author","Hermann, D. M."],["dc.contributor.author","Bähr, M."],["dc.date.accessioned","2017-09-07T11:44:07Z"],["dc.date.available","2017-09-07T11:44:07Z"],["dc.date.issued","2004"],["dc.description.abstract","The superoxide dismutase 1 (SOD1) G93A mouse was recently established as transgenic model of amyotrophic lateral sclerosis. We were interested to know whether the SOD1 G93A mutation promotes neuronal injury after intraluminal middle cerebral artery thread occlusion and/or retinal ganglion cell (RGC) axotomy in mice, which are highly reproducible and clinically relevant in vivo models of acute and subacute neuronal degeneration, respectively. In our experiments, G93A mutant SOD1 neither influenced ischemic injury after 90 or 30 min of focal ischemia, nor had an impact on the severity of RGC degeneration after optic nerve transection, when human SOD1 G93A mutant mice were compared to human wild-type SOD1 mice. Our data indicate that the clinically relevant SOD1 G93A mutation, which leads to amyotrophic lateral sclerosis in humans and mice, does not necessarily worsen neuronal degeneration in other pathologies. Thus, the G93A mutation may be counterbalanced in non-motor neurons of young animals, and region-specific and age-related factors may be necessary so that neurodegeneration is re-enforced. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neuroscience.2004.06.064"],["dc.identifier.gro","3144026"],["dc.identifier.isi","000223944900013"],["dc.identifier.pmid","15350647"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1605"],["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","0306-4522"],["dc.title","The superoxide dismutase1 (SOD1) G93A mutation does not promote neuronal injury after focal brain ischemia and optic nerve transection in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","489"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular and Cellular Neuroscience"],["dc.bibliographiccitation.lastpage","502"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Kussmaul, L"],["dc.contributor.author","Grotsch, P."],["dc.contributor.author","Hecke, A."],["dc.contributor.author","Rohde, Gundula"],["dc.contributor.author","Romig, H."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Gillardon, Frank"],["dc.date.accessioned","2017-09-07T11:44:13Z"],["dc.date.available","2017-09-07T11:44:13Z"],["dc.date.issued","2003"],["dc.description.abstract","Previous studies suggested that pro-apoptotic stimuli may trigger a fatal reactivation of cell cycle elements in postmitotic neurons. Supporting this hypothesis, small molecule inhibitors of cyclin-dependent kinases (CDKs), which are known primarily as cell cycle regulators, are neuroprotective. However, available CDK inhibitors cannot discriminate between the different members of the CDK family and inhibit also CDK5, which is not involved in cell cycle control. Testing a new class of CDK inhibitors, we find that inhibitory activity against CDK5, but not cell cycle-relevant CDKs, confers neuroprotection. Moreover, we demonstrate that cleavage of the CDK5 activator protein p35 to p25 is associated with CDK5 overactivation after focal cerebral ischemia, but not in other models used in this study. We find that blocking CDK5 activity, but not caspase inhibition, protects mitochondria! integrity of lesioned neurons. Thus, in our models, CDK5, rather than cell cycle-relevant CDKs, activates neuronal cell death pathways upstream of mitochondrial dysfunction, and inhibition of CDK5 may promote functional long-term rescue of injured neurons. Moreover, we present the first CDK5-selective small molecule inhibitor, lacking unwanted cytostatic effects due to cross-inhibition of mitotic CDKs. (C) 2003 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/S1044-7431(03)00221-5"],["dc.identifier.gro","3144055"],["dc.identifier.isi","000186164400019"],["dc.identifier.pmid","14572469"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1637"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1044-7431"],["dc.title","Inhibition of CDK5 is protective in necrotic and apoptotic paradigms of neuronal cell death and prevents mitochondrial dysfunction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","313"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","323"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Bartels, Claudia"],["dc.contributor.author","Pölking, Esther"],["dc.contributor.author","Dietrich, Jeannine"],["dc.contributor.author","Rohde, Gundula"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Mertens, Nina"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Bohn, Matthias"],["dc.contributor.author","Hüther, Gerald"],["dc.contributor.author","Schneider, Armin"],["dc.contributor.author","Bach, Alfred"],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Hardeland, Rüdiger"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:31Z"],["dc.date.available","2017-09-07T11:46:31Z"],["dc.date.issued","2006"],["dc.description.abstract","Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron disease of different etiologies, with oxidative stress as a common molecular denominator of disease progression. Melatonin is an amphiphilic molecule with a unique spectrum of antioxidative effects not conveyed by classical antioxidants. In preparation of a possible future clinical trial, we explored the potential of melatonin as neuroprotective compound and antioxidant in: (1) cultured motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)-transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS."],["dc.identifier.doi","10.1111/j.1600-079X.2006.00377.x"],["dc.identifier.gro","3150526"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7299"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.issn","0742-3098"],["dc.title","Reduced oxidative damage in ALS by high-dose enteral melatonin treatment"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","unknown"],["dspace.entity.type","Publication"]]