Reinert, Marie-Christine

[["dc.bibliographiccitation.artnumber","64"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Orphanet Journal of Rare Diseases"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Catarino, Claudia B."],["dc.contributor.author","Klopstock, Thomas"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Schittkowski, Michael Peter"],["dc.contributor.author","Wilichowski, Ekkehard"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2021-04-14T08:28:08Z"],["dc.date.available","2021-04-14T08:28:08Z"],["dc.date.issued","2021"],["dc.date.updated","2022-07-29T12:17:42Z"],["dc.description.abstract","Background Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and characterized by acute or subacute painless visual loss. Environmental factors reported to trigger visual loss in LHON mutation carriers include smoking, heavy intake of alcohol, raised intraocular pressure, and some drugs, including several carbonic anhydrase inhibitors. The antiepileptic drug sulthiame (STM) is effective especially in focal seizures, particularly in benign epilepsy of childhood with centrotemporal spikes, and widely used in pediatric epileptology. STM is a sulfonamide derivate and an inhibitor of mammalian carbonic anhydrase isoforms I–XIV. Results We describe two unrelated patients, an 8-year-old girl and an 11-year-old boy, with cryptogenic focal epilepsy, who suffered binocular (subject #1) or monocular (subject #2) visual loss in close temporal connection with starting antiepileptic pharmacotherapy with STM. In both subjects, visual loss was due to LHON. We used real-time respirometry in fibroblasts derived from LHON patients carrying the same mitochondrial mutations as our two subjects to investigate the effect of STM on oxidative phosphorylation. Oxygen consumption rate in fibroblasts from a healthy control was not impaired by STM compared with a vehicle control. In contrast, fibroblasts carrying the m.14484T>C or the m.3460G>A LHON mutation displayed a drastic reduction of the respiration rate when treated with STM compared to vehicle control. Conclusions Our observations point to a causal relationship between STM treatment and onset or worsening of visual failure in two subjects with LHON rather than pure coincidence. We conclude that antiepileptic medication with STM may pose a risk for visual loss in LHON mutation carriers and should be avoided in these patients."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Orphanet Journal of Rare Diseases. 2021 Feb 04;16(1):64"],["dc.identifier.doi","10.1186/s13023-021-01690-y"],["dc.identifier.pmid","33541401"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82509"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/219"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/102"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen"],["dc.relation.eissn","1750-1172"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Sulthiame"],["dc.subject","Carbonic anhydrase inhibitor"],["dc.subject","Adverse effects"],["dc.subject","Leber hereditary optic neuropathy"],["dc.subject","LHON"],["dc.subject","Oxygen consumption rate"],["dc.title","Sulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","930"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Muscle & Nerve"],["dc.bibliographiccitation.lastpage","936"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Klinker, Florian"],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Hesse, Stefan"],["dc.contributor.author","Liebetanz, David"],["dc.date.accessioned","2018-11-07T08:49:18Z"],["dc.date.available","2018-11-07T08:49:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Introduction: To test the hypothesis that the efficacy of botulinum toxin depends on the activity of the neuromuscular junction, we developed an in vivo paradigm to determine the degree and duration of low-dose botulinum toxin-induced focal paresis in mice. Methods: We combined an automated wheel-running paradigm with low-dose botulinum toxin injections into the calf muscles of wild-type mice. Half of the mice were injected either before the nightly running or before the daily resting period. Results: After botulinum toxin injections, running distance and maximum velocity decreased dose-dependently. The degree and duration of decrease between the respective groups with regard to the time-points of injection were identical. Conclusions: This in vivo paradigm quantifies the degree of otherwise clinically inapparent botulinum toxin-induced focal calf muscle paresis. Increased muscle activity after low-dose injections does not influence the efficacy of botulinum toxin in normal muscles. Muscle Nerve 44: 930-936, 2011"],["dc.identifier.doi","10.1002/mus.22210"],["dc.identifier.isi","000297938800015"],["dc.identifier.pmid","22102464"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21429"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0148-639X"],["dc.title","BOTULINUM TOXIN-INDUCED FOCAL PARESIS IN MICE IS UNAFFECTED BY MUSCLE ACTIVITY"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2803"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.lastpage","2807"],["dc.bibliographiccitation.volume","173"],["dc.contributor.author","Weissbach, Susann"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Krätzner, Ralph"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Rosenbaum, Thorsten"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2018-04-23T11:47:26Z"],["dc.date.available","2018-04-23T11:47:26Z"],["dc.date.issued","2017"],["dc.description.abstract","Cabezas type of X‐linked syndromic intellectual disability (MRXSC; MIM300354) is a rare X‐linked recessive intellectual disability characterized primarily by intellectual disability, short stature, hypogonadism, and gait abnormalities. It is caused by a wide spectrum of hemizygous variants in CUL4B. In a 10‐year‐old boy with an exceptional leukoencephalopathy pattern, we identified a new missense variant p.Leu329Gln in CUL4B using “Mendeliome” sequencing. However, his phenotype does not include the severe characteristics currently known for MRXSC. We discuss the divergent phenotype and propose a potential connection between the different CUL4B variants and corresponding phenotypes in the context of the current literature as well as 3D homology modeling."],["dc.identifier.doi","10.1002/ajmg.a.38390"],["dc.identifier.gro","3142217"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13339"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","1552-4825"],["dc.title","A new CUL4B variant associated with a mild phenotype and an exceptional pattern of leukoencephalopathy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","89"],["dc.bibliographiccitation.journal","Toxicon"],["dc.bibliographiccitation.lastpage","90"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Reinert, M. C."],["dc.contributor.author","Klinker, Florian"],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Hesse, Stefan"],["dc.contributor.author","Liebetanz, David"],["dc.date.accessioned","2018-11-07T09:23:39Z"],["dc.date.available","2018-11-07T09:23:39Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1016/j.toxicon.2012.07.089"],["dc.identifier.isi","000320075500077"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29632"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Santa Fe, NM"],["dc.relation.issn","0041-0101"],["dc.title","Novel in vivo test shows low-dosage botulinum toxin-induced focal calf muscle paresis is independent of increased muscle activity in wild-type mice"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","374"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Experimental Neurology"],["dc.bibliographiccitation.lastpage","379"],["dc.bibliographiccitation.volume","235"],["dc.contributor.author","Schmitz, Thomas"],["dc.contributor.author","Endesfelder, Stefanie"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Klinker, Florian"],["dc.contributor.author","Müller, Susann"],["dc.contributor.author","Bührer, Christoph"],["dc.contributor.author","Liebetanz, David"],["dc.date.accessioned","2018-11-07T09:10:49Z"],["dc.date.available","2018-11-07T09:10:49Z"],["dc.date.issued","2012"],["dc.description.abstract","In preterm infants, the risk to develop attention-deficit/hyperactivity disorder is 3 to 4-fold higher than in term infants. Moreover, preterm infants exhibit deficits in motor coordination and balance. Based on clinical data, higher oxygen levels in preterm infants lead to worse neurological outcome, and experimental hyperoxia causes wide-ranging cerebral changes in neonatal rodents. We hypothesize that hyperoxia in the immature brain may affect motor activity in preterm infants. We subjected newborn mice from P6 to P8 to 48 h of hyperoxia (80% O-2) and tested motor activity in running wheels starting at adolescent age P30. Subsequently, from P44 to P53, regular wheels were replaced by complex wheels with variable crossbar positions to assess motor coordination deficits. MRI with diffusion tensor imaging was performed in the corpus callosum to determine white matter diffusivity in mice after hyperoxia at ages P30 and P53 in comparison to control animals. Adolescent mice after neonatal hyperoxia revealed significantly higher values for maximum velocity and mean velocity in regular wheels than controls (P<0.05). In the complex running wheels, however, maximum velocity was decreased in animals after hyperoxia, as compared to controls (P<0.05). Decreased fractional anisotropy and increased radial diffusion coefficient were observed in the corpus callosum of P30 and P53 mice after neonatal hyperoxia compared to control mice. Hyperoxia in the immature brain causes hyperactivity, motor coordination deficits, and impaired white matter diffusivity in adolescent and young adult mice. (C) 2012 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Medical Faculty, University of Gottingen"],["dc.identifier.doi","10.1016/j.expneurol.2012.03.002"],["dc.identifier.isi","000303430400039"],["dc.identifier.pmid","22449476"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26581"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","0014-4886"],["dc.title","Adolescent hyperactivity and impaired coordination after neonatal hyperoxia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e980"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Schulz, R."],["dc.contributor.author","Streller, F."],["dc.contributor.author","Scheel, Andreas Hans"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Reinert, M. C."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Marchenko, N. D."],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T09:46:24Z"],["dc.date.available","2018-11-07T09:46:24Z"],["dc.date.issued","2014"],["dc.description.abstract","Overexpression of the human epidermal growth factor receptor-2 (HER2) in breast cancer strongly correlates with aggressive tumors and poor prognosis. Recently, a positive correlation between HER2 and MIF (macrophage migration inhibitory factor, a tumor-promoting protein and heat-shock protein 90 (HSP90) client) protein levels was shown in cancer cells. However, the underlying mechanistic link remained unknown. Here we show that overexpressed HER2 constitutively activates heat-shock factor 1 (HSF1), the master transcriptional regulator of the inducible proteotoxic stress response of heat-shock chaperones, including HSP90, and a crucial factor in initiation and maintenance of the malignant state. Inhibiting HER2 pharmacologically by Lapatinib (a dual HER2/epidermal growth factor receptor inhibitor) or CP724.714 (a specific HER2 inhibitor), or by knockdown via siRNA leads to inhibition of phosphoactivated Ser326 HSF1, and subsequently blocks the activity of the HSP90 chaperone machinery in HER2-overexpressing breast cancer lines. Consequently, HSP90 clients, including MIF, AKT, mutant p53 and HSF1 itself, become destabilized, which in turn inhibits tumor proliferation. Mechanistically, HER2 signals via the phosphoinositide-3kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) axis to induce activated pSer326 HSF1. Heat-shock stress experiments confirm this functional link between HER2 and HSF1, as HER2 (and PI3K) inhibition attenuate the HSF1-mediated heat-shock response. Importantly, we confirmed this axis in vivo. In the mouse model of HER2-driven breast cancer, ErbB2 inhibition by Lapatinib strongly suppresses tumor progression, and this is associated with inactivation of the HSF1 pathway. Moreover, ErbB2-overexpressing cancer cells derived from a primary mouse ErbB2 tumor also show HSF1 inactivation and HSP90 client destabilization in response to ErbB2 inhibition. Furthermore, in HER2-positive human breast cancers HER2 levels strongly correlate with pSer326 HSF1 activity. Our results show for the first time that HER2/ErbB2 overexpression controls HSF1 activity, with subsequent stabilization of numerous tumor-promoting HSP90 clients such as MIF, AKT and HSF1 itself, thereby causing a robust promotion in tumor growth in HER2-positive breast cancer."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.1038/cddis.2013.508"],["dc.identifier.isi","000332222700004"],["dc.identifier.pmid","24384723"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9556"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34861"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["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.title","HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","NeuroToxicology"],["dc.bibliographiccitation.lastpage","8"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Krez, Nadja"],["dc.contributor.author","Liebetanz, David"],["dc.contributor.author","Rummel, Andreas"],["dc.date.accessioned","2018-11-07T10:26:22Z"],["dc.date.available","2018-11-07T10:26:22Z"],["dc.date.issued","2017"],["dc.description.abstract","The highly potent Botulinum neurotoxins (BoNT) are successful drugs to treat neuromuscular disorders. Efforts are being made to further reduce the injected BoNT dose and to lengthen the interval between treatments. Detailed knowledge of the BoNT structure-activity relationship (SAR) allows combining the best features of the different BoNT serotypes. Of all seven BoNT serotypes A-G, BoNT/A displays the highest potency despite low neuronal binding affinity, while BoNT/B exhibits much higher affinity. Recently, a new BoNT/AB hybrid (AABB) was constructed comprising the catalytic and translocation domain of BoNT/A and the 50 kDa cell binding domain of BoNT/B. Here, we compared BoNT/A wild-type (AAAA) and AABB with regard to ex vivo potency and in vivo potency, efficacy and duration of action using the mouse phrenic nerve hemidiaphragm assay and the murine running wheel assay, respectively. The ex vivo potency of AABB was found to be 8.4-fold higher than that of AAAA. For the latter, two and 5 pg each of AAAA and AABB, respectively, were bilaterally injected into the calf muscles and mouse running wheel performance was automatically monitored during the following weeks to determine potency, efficacy and duration. Mice displayed a dose-dependent impairment of running performance. AABB showed potency, efficacy and duration equal to AAAA demonstrating successful exchange of the cell binding domain. AABB might combine the higher potency and longer duration of BoNT/A with the target specificity for the autonomic nervous system of BoNT/B. AABB might therefore constitute an improved treatment option for acetylcholine-mediated autonomic disorders such as hypersalivation or hyperhidrosis. (C) 2016 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.neuro.2016.12.008"],["dc.identifier.isi","000399061900001"],["dc.identifier.pmid","28043867"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43028"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1872-9711"],["dc.relation.issn","0161-813X"],["dc.title","BoNT/AB hybrid maintains similar duration of paresis as BoNT/A wild-type in murine running wheel assay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e749"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neurology - Neuroimmunology Neuroinflammation"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Benkert, Pascal"],["dc.contributor.author","Wuerfel, Jens"],["dc.contributor.author","Michalak, Zuzanna"],["dc.contributor.author","Ruberte, Esther"],["dc.contributor.author","Barro, Christian"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Stark, Wiebke"],["dc.contributor.author","Kropshofer, Harald"],["dc.contributor.author","Tomic, Davorka"],["dc.contributor.author","Leppert, David"],["dc.contributor.author","Kuhle, Jens"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-04-14T08:25:14Z"],["dc.date.available","2021-04-14T08:25:14Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1212/NXI.0000000000000749"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17477"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81564"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2332-7812"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","45"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuroscience Methods"],["dc.bibliographiccitation.lastpage","48"],["dc.bibliographiccitation.volume","205"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Klinker, Florian"],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Hesse, Stefan"],["dc.contributor.author","Liebetanz, David"],["dc.date.accessioned","2018-11-07T09:12:06Z"],["dc.date.available","2018-11-07T09:12:06Z"],["dc.date.issued","2012"],["dc.description.abstract","Tetanus neurotoxin (TeNT) enhances activity of motoneurons by blocking spinal inhibitory interneurons. Based on this pathomechanism, we propose that low-dosage intramuscular injections of TeNT could serve as a specific treatment for central paretic muscles. However in vivo TeNT research is restricted because of the fear of triggering widespread muscle spasms. In addition, no reliable test to measure the in vivo toxicity of low-dosage TeNT is available. We introduce a novel wheel running-based paradigm with mice to quantify functional effects and thus the toxicity of low-dosage TeNT in vivo. We accustomed three groups of wildtype mice (n=14) to using a complex running wheel with irregularly spaced crossbars. Each group received an injection with a different low-dosage of TeNT (0.15 ng, 0.1 ng or 0.05 ng TeNT) into both tibialis anterior muscles. The maximum running velocity and accumulative running time of the groups were recorded during the following weeks. Three days after TeNT injections, the mice exhibited an increase in muscle tone of the injected tibialis anterior muscles but no generalized symptoms. However, we found that normal running in the complex wheel set-up was disturbed such that the maximum running velocity and running time of the mice decreased with the size of the dose. This effect peaked on the fifth and sixth nights after injection and returned to baseline level again within the next two weeks. With this novel in vivo automated paradigm we can accurately and objectively quantify the duration and degree of TeNT-induced focal increase in muscle tone. (C) 2012 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jneumeth.2011.12.019"],["dc.identifier.isi","000301688600006"],["dc.identifier.pmid","22227534"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26874"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-0270"],["dc.title","Accurate quantification of tetanus neurotoxin-induced focal spasticity in mice using complex running wheels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","216"],["dc.bibliographiccitation.journal","Neuroscience Letters"],["dc.bibliographiccitation.lastpage","221"],["dc.bibliographiccitation.volume","627"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Manig, Anja"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Moennich, Angelika"],["dc.contributor.author","Liebetanz, David"],["dc.date.accessioned","2018-11-07T10:10:20Z"],["dc.date.available","2018-11-07T10:10:20Z"],["dc.date.issued","2016"],["dc.description.abstract","Three botulinum neurotoxin type A (BoNT/A) products, incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA, all manufactured by different methods, are employed in clinical practice. Comparing the three BoNT/A products is difficult because their concentrations and volumes differ and the precise dose equivalence ratio is not known. We aimed to compare the neurotoxic potencies by a systematic analysis of injected volume and dose. The potency of BoNT in inducing hind limb paresis was assessed by analyzing the wheel-running performance of mice. To standardize the volume, the effect of an identical dose of incobotulinumtoxinA dissolved in different volumes of saline (15,10, 5, and 2 mu l) was studied in four groups of mice (n = 13-15). The potencies of the BoNT products were then compared by injecting identical volumes (10 mu l) containing different doses into both hind leg muscles. Mice injected with incobotulinumtoxinA showed a volume-dependent reduction in wheel-running, with larger volumes inducing more intense paresis. A standardized volume containing the same number of mouse units of the BoNT/A products produced different degrees of paresis. The conversion ratio of incobotulinumtoxinA and onabotulinumtoxinA is estimated to be between 1:0.75 and 1:0.5. OnabotulinumtoxinA displayed a two-fold greater potency than abobotulinumtoxinA. Doses of onabotulinumtoxinA and abobotulinumtoxinA that produce an identical severity of pareses even result in the same duration of pareses. This wheel-running assay allows one to compare the neurotoxic potency of different volumes and doses of the BoNT products in vivo. Our results argue against common clinical practice because incobotulinumtoxinA and onabotulinumtoxinA are not readily interchangeable and a two-fold dose of abobotulinumtoxinA is needed to induce an effect identical to onabotulinumtoxinA. In addition, this emphasizes that the duration of BoNT-induced effect is the same as long as equipotent doses of BoNT are injected. (C) 2016 Elsevier Ireland Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neulet.2016.06.001"],["dc.identifier.isi","000380418400033"],["dc.identifier.pmid","27268041"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39832"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.relation.issn","1872-7972"],["dc.relation.issn","0304-3940"],["dc.title","In-vivo comparison of the neurotoxic potencies of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]