Zschüntzsch, Jana

[["dc.bibliographiccitation.firstpage","918"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","11"],["dc.contributor.affiliation","Svetlove, Angelika; 1Translational Molecular Imaging, Max-Planck Institute for Multidisciplinary Sciences, City Campus, 37075 Göttingen, Germany; anzhelika.svetlova@mpinat.mpg.de (A.S.); markus@mpinat.mpg.de (M.A.M.); falves@gwdg.de (F.A.)"],["dc.contributor.affiliation","Albers, Jonas; 2X-ray Based Preclinical Imaging Technologies, Institute for Diagnostic and Interventional Radiology, University Medical Center, 37075 Göttingen, Germany; jonas.albers@embl-hamburg.de"],["dc.contributor.affiliation","Hülsmann, Swen; 3Central Breathing Control, Clinic for Anesthesiology, University Medical Center, 37075 Göttingen, Germany; shuelsm2@uni-goettingen.de"],["dc.contributor.affiliation","Markus, Marietta Andrea; 1Translational Molecular Imaging, Max-Planck Institute for Multidisciplinary Sciences, City Campus, 37075 Göttingen, Germany; anzhelika.svetlova@mpinat.mpg.de (A.S.); markus@mpinat.mpg.de (M.A.M.); falves@gwdg.de (F.A.)"],["dc.contributor.affiliation","Zschüntzsch, Jana; 4Neuromuscular Disease Research, Clinic for Neurology, University Medical Center, 37075 Göttingen, Germany; j.zschuentzsch@med.uni-goettingen.de"],["dc.contributor.affiliation","Alves, Frauke; 1Translational Molecular Imaging, Max-Planck Institute for Multidisciplinary Sciences, City Campus, 37075 Göttingen, Germany; anzhelika.svetlova@mpinat.mpg.de (A.S.); markus@mpinat.mpg.de (M.A.M.); falves@gwdg.de (F.A.)"],["dc.contributor.affiliation","Dullin, Christian; 2X-ray Based Preclinical Imaging Technologies, Institute for Diagnostic and Interventional Radiology, University Medical Center, 37075 Göttingen, Germany; jonas.albers@embl-hamburg.de"],["dc.contributor.author","Svetlove, Angelika"],["dc.contributor.author","Albers, Jonas"],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Markus, Marietta Andrea"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Dullin, Christian"],["dc.date.accessioned","2022-04-01T10:00:28Z"],["dc.date.available","2022-04-01T10:00:28Z"],["dc.date.issued","2022"],["dc.date.updated","2022-04-08T11:23:03Z"],["dc.description.abstract","Duchenne muscular dystrophy (DMD) is the most common x-chromosomal inherited dystrophinopathy which leads to progressive muscle weakness and a premature death due to cardiorespiratory dysfunction. The mdx mouse lacks functional dystrophin protein and has a comparatively human-like diaphragm phenotype. To date, diaphragm function can only be inadequately mapped in preclinical studies and a simple reliable translatable method of tracking the severity of the disease still lacks. We aimed to establish a sensitive, reliable, harmless and easy way to assess the effects of respiratory muscle weakness and subsequent irregularity in breathing pattern. Optical respiratory dynamics tracking (ORDT) was developed utilising a camera to track the movement of paper markers placed on the thoracic-abdominal region of the mouse. ORDT successfully distinguished diseased mdx phenotype from healthy controls by measuring significantly higher expiration constants (k) in mdx mice compared to wildtype (wt), which were also observed in the established X-ray based lung function (XLF). In contrast to XLF, with ORDT we were able to distinguish distinct fast and slow expiratory phases. In mdx mice, a larger part of the expiratory marker displacement was achieved in this initial fast phase as compared to wt mice. This phenomenon could not be observed in the XLF measurements. We further validated the simplicity and reliability of our approach by demonstrating that it can be performed using free-hand smartphone acquisition. We conclude that ORDT has a great preclinical potential to monitor DMD and other neuromuscular diseases based on changes in the breathing patterns with the future possibility to track therapy response."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/cells11050918"],["dc.identifier.pii","cells11050918"],["dc.identifier.pmid","35269540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105437"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/535"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2073-4409"],["dc.relation.workinggroup","RG Alves (Translationale Molekulare Bildgebung)"],["dc.rights","CC BY 4.0"],["dc.title","Non-Invasive Optical Motion Tracking Allows Monitoring of Respiratory Dynamics in Dystrophin-Deficient Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","18683"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.lastpage","18713"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","De Paepe, Boel"],["dc.contributor.author","Zschuentzsch, Jana"],["dc.date.accessioned","2018-11-07T09:53:26Z"],["dc.date.available","2018-11-07T09:53:26Z"],["dc.date.issued","2015"],["dc.description.abstract","The idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of chronic disorders that include dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). They represent distinct pathological entities that, most often, share predominant inflammation in muscle tissue. Many of the immunopathogenic processes behind the IIM remain poorly understood, but the crucial role of cytokines as essential regulators of the intramuscular build-up of inflammation is undisputed. This review describes the extensive cytokine network within IIM muscle, characterized by strong expression of Tumor Necrosis Factors (TNF, LT, BAFF), Interferons (IFN//), Interleukins (IL-1/6/12/15/18/23) and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21). Current therapeutic strategies and the exploration of potential disease modifying agents based on manipulation of the cytokine network are provided. Reported responses to anti-TNF treatment in IIM are conflicting and new onset DM/PM has been described after administration of anti-TNF agents to treat other diseases, pointing to the complex effects of TNF neutralization. Treatment with anti-IFN has been shown to suppress the IFN type 1 gene signature in DM/PM patients and improve muscle strength. Beneficial effects of anti-IL-1 and anti-IL-6 therapy have also been reported. Cytokine profiling in IIM aids the development of therapeutic strategies and provides approaches to subtype patients for treatment outcome prediction."],["dc.description.sponsorship","U4 network OSMYO; Ghent University Medical Faculty"],["dc.identifier.doi","10.3390/ijms160818683"],["dc.identifier.isi","000366826100104"],["dc.identifier.pmid","26270565"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12760"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36330"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e17910"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Zschuentzsch, Jana"],["dc.contributor.author","Nadrigny, Fabien"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Neusch, Clemens"],["dc.date.accessioned","2018-11-07T08:58:04Z"],["dc.date.available","2018-11-07T08:58:04Z"],["dc.date.issued","2011"],["dc.description.abstract","Mutations in the enzyme superoxide dismutase-1 (SOD1) cause hereditary variants of the fatal motor neuronal disease Amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous: neurotoxicity is derived not only from mutant motor neurons but also from mutant neighbouring non-neuronal cells. In vivo imaging by two-photon laser-scanning microscopy was used to compare the role of microglia/macrophage-related neuroinflammation in the CNS and PNS using ALS-linked transgenic SOD1(G93A) mice. These mice contained labeled projection neurons and labeled microglia/macrophages. In the affected lateral spinal cord (in contrast to non-affected dorsal columns), different phases of microglia-mediated inflammation were observed: highly reactive microglial cells in preclinical stages (in 60-day-old mice the reaction to axonal transection was similar to 180% of control) and morphologically transformed microglia that have lost their function of tissue surveillance and injury-directed response in clinical stages (reaction to axonal transection was lower than 50% of control). Furthermore, unlike CNS microglia, macrophages of the PNS lack any substantial morphological reaction while preclinical degeneration of peripheral motor axons and neuromuscular junctions was observed. We present in vivo evidence for a different inflammatory activity of microglia and macrophages: an aberrant neuroinflammatory response of microglia in the CNS and an apparently mainly neurodegenerative process in the PNS."],["dc.identifier.doi","10.1371/journal.pone.0017910"],["dc.identifier.isi","000288545100043"],["dc.identifier.pmid","21437247"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23554"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS"],["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.artnumber","e43963"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PlosOne"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Scheffel, Jörg"],["dc.contributor.author","Göricke, Bettina"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Le Meur, Karim"],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Neusch, Clemens"],["dc.date.accessioned","2019-07-09T11:53:39Z"],["dc.date.available","2019-07-09T11:53:39Z"],["dc.date.issued","2012"],["dc.description.abstract","Mutations in SOD1 cause hereditary variants of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous, with toxicity deriving also from glia. In particular, microglia contribute to disease progression. Methylene blue (MB) inhibits the effect of nitric oxide, which mediates microglial responses to injury. In vivo 2P-LSM imaging was performed in ALS-linked transgenic SOD1G93A mice to investigate the effect of MB on microglia-mediated inflammation in the spinal cord. Local superfusion of the lateral spinal cord with MB inhibited the microglial reaction directed at a laser-induced axon transection in control and SOD1G93A mice. In vitro, MB at high concentrations inhibited cytokine and chemokine release from microglia of control and advanced clinical SOD1G93A mice. Systemic MB-treatment of SOD1G93A mice at early preclinical stages significantly delayed disease onset and motor dysfunction. However, an increase of MB dose had no additional effect on disease progression; this was unexpected in view of the local anti-inflammatory effects. Furthermore, in vivo imaging of systemically MB-treated mice also showed no alterations of microglia activity in response to local lesions. Thus although systemic MB treatment had no effect on microgliosis, instead, its use revealed an important influence on motor neuron survival as indicated by an increased number of lumbar anterior horn neurons present at the time of disease onset. Thus, potentially beneficial effects of locally applied MB on inflammatory events contributing to disease progression could not be reproduced in SOD1G93A mice via systemic administration, whereas systemic MB application delayed disease onset via neuroprotection."],["dc.format.extent","13"],["dc.identifier.doi","10.1371/journal.phone.0043963"],["dc.identifier.fs","592827"],["dc.identifier.pmid","22952827"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7861"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60471"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Influence of Methylene Blue on Microglia-Induced Inflammation and Motor Neuron Degeneration in the SOD1G93A Model for ALS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1233"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","11"],["dc.contributor.affiliation","Zschüntzsch, Jana; 1Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany; stefanie.meyer@med.uni-goettingen.de (S.M.); karsten.kummer@med.uni-goettingen.de (K.K.); matthias.schmidt6@stud.uni-goettingen.de (M.S.)"],["dc.contributor.affiliation","Meyer, Stefanie; 1Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany; stefanie.meyer@med.uni-goettingen.de (S.M.); karsten.kummer@med.uni-goettingen.de (K.K.); matthias.schmidt6@stud.uni-goettingen.de (M.S.)"],["dc.contributor.affiliation","Shahriyari, Mina; 2Institute of Pharmacology and Toxicology, University Medical Center Goettingen, 37075 Goettingen, Germany; mina.shahriyari@med.uni-goettingen.de"],["dc.contributor.affiliation","Kummer, Karsten; 1Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany; stefanie.meyer@med.uni-goettingen.de (S.M.); karsten.kummer@med.uni-goettingen.de (K.K.); matthias.schmidt6@stud.uni-goettingen.de (M.S.)"],["dc.contributor.affiliation","Schmidt, Matthias; 1Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany; stefanie.meyer@med.uni-goettingen.de (S.M.); karsten.kummer@med.uni-goettingen.de (K.K.); matthias.schmidt6@stud.uni-goettingen.de (M.S.)"],["dc.contributor.affiliation","Kummer, Susann; 4Risk Group 4 Pathogens–Stability and Persistence, Biosafety Level-4 Laboratory, Center for Biological Threats and Special Pathogens, Robert Koch Institute, 13353 Berlin, Germany; kummers@rki.de"],["dc.contributor.affiliation","Tiburcy, Malte; 2Institute of Pharmacology and Toxicology, University Medical Center Goettingen, 37075 Goettingen, Germany; mina.shahriyari@med.uni-goettingen.de"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Meyer, Stefanie"],["dc.contributor.author","Shahriyari, Mina"],["dc.contributor.author","Kummer, Karsten"],["dc.contributor.author","Schmidt, Matthias"],["dc.contributor.author","Kummer, Susann"],["dc.contributor.author","Tiburcy, Malte"],["dc.date.accessioned","2022-05-02T08:09:34Z"],["dc.date.available","2022-05-02T08:09:34Z"],["dc.date.issued","2022"],["dc.date.updated","2022-05-05T12:22:52Z"],["dc.description.abstract","Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/cells11071233"],["dc.identifier.pii","cells11071233"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107410"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/428"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.eissn","2073-4409"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.title","The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1018"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Cachexia, Sarcopenia and Muscle"],["dc.bibliographiccitation.lastpage","1031"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Jouvenal, Pia Vanessa"],["dc.contributor.author","Zhang, Yaxin"],["dc.contributor.author","Klinker, Florian"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Liebetanz, David"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Brinkmeier, Heinrich"],["dc.contributor.author","Schmidt, Jens"],["dc.date.accessioned","2021-04-14T08:26:53Z"],["dc.date.available","2021-04-14T08:26:53Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Background Duchenne muscular dystrophy (DMD) is a progressive muscle‐wasting disease caused by mutations in the dystrophin gene, which leads to structural instability of the dystrophin–glycoprotein‐complex with subsequent muscle degeneration. In addition, muscle inflammation has been implicated in disease progression and therapeutically addressed with glucocorticosteroids. These have numerous adverse effects. Treatment with human immunoglobulin G (IgG) improved clinical and para‐clinical parameters in the early disease phase in the well‐established mdx mouse model. The aim of the present study was to confirm the efficacy of IgG in a long‐term pre‐clinical study in mdx mice. Methods IgG (2 g/kg body weight) or NaCl solution as control was administered monthly over 18 months by intraperitoneal injection in mdx mice beginning at 3 weeks of age. Several clinical outcome measures including endurance, muscle strength, and echocardiography were assessed. After 18 months, the animals were sacrificed, blood was collected for analysis, and muscle samples were obtained for ex vivo muscle contraction tests, quantitative PCR, and histology. Results IgG significantly improved the daily voluntary running performance (1.9 m more total daily running distance, P \\u0026lt; 0.0001) and slowed the decrease in grip strength by 0.1 mN, (P = 0.018). IgG reduced fatigability of the diaphragm (improved ratio to maximum force by 0.09 ± 0.04, P = 0.044), but specific tetanic force remained unchanged in the ex vivo muscle contraction test. Cardiac function was significantly better after IgG, especially fractional area shortening (P = 0.012). These results were accompanied by a reduction in cardiac fibrosis and the infiltration of T cells (P = 0.0002) and macrophages (P = 0.0027). In addition, treatment with IgG resulted in a significant reduction of the infiltration of T cells (P ≤ 0.036) in the diaphragm, gastrocnemius, quadriceps, and a similar trend in tibialis anterior and macrophages (P ≤ 0.045) in gastrocnemius, quadriceps, tibialis anterior, and a similar trend in the diaphragm, as well as a decrease in myopathic changes as reflected by a reduced central nuclear index in the diaphragm, tibialis anterior, and quadriceps (P ≤ 0.002 in all). Conclusions The present study underscores the importance of an inflammatory contribution to the disease progression of DMD. The data demonstrate the long‐term efficacy of IgG in the mdx mouse. IgG is well tolerated by humans and could preferentially complement gene therapy in DMD. The data call for a clinical trial with IgG in DMD."],["dc.description.sponsorship","CSL Behring http://dx.doi.org/10.13039/100008322"],["dc.identifier.doi","10.1002/jcsm.12569"],["dc.identifier.pmid","32436338"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17353"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82110"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/355"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","2190-6009"],["dc.relation.issn","2190-5991"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Long‐term human IgG treatment improves heart and muscle function in a mouse model of Duchenne muscular dystrophy"],["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","3251"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","23"],["dc.contributor.affiliation","Merckx, Caroline; 1Department of Neurology, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium; caroline.merckx@ugent.be (C.M.); gwenny.cosemans@ugent.be (G.C.); jan.debleecker@ugent.be (J.L.D.B.)"],["dc.contributor.affiliation","Cosemans, Gwenny; 1Department of Neurology, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium; caroline.merckx@ugent.be (C.M.); gwenny.cosemans@ugent.be (G.C.); jan.debleecker@ugent.be (J.L.D.B.)"],["dc.contributor.affiliation","Zschüntzsch, Jana; 2Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; j.zschuentzsch@med.uni-goettingen.de (J.Z.); j.schmidt@gmx.org (J.S.)"],["dc.contributor.affiliation","Raedt, Robrecht; 34BRAIN, Institute for Neuroscience, Department Head and Skin, Ghent University, 9000 Ghent, Belgium; robrecht.raedt@ugent.be"],["dc.contributor.affiliation","Schmidt, Jens; 2Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; j.zschuentzsch@med.uni-goettingen.de (J.Z.); j.schmidt@gmx.org (J.S.)"],["dc.contributor.affiliation","De Paepe, Boel; 1Department of Neurology, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium; caroline.merckx@ugent.be (C.M.); gwenny.cosemans@ugent.be (G.C.); jan.debleecker@ugent.be (J.L.D.B.)"],["dc.contributor.affiliation","De Bleecker, Jan L.; 1Department of Neurology, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium; caroline.merckx@ugent.be (C.M.); gwenny.cosemans@ugent.be (G.C.); jan.debleecker@ugent.be (J.L.D.B.)"],["dc.contributor.author","Merckx, Caroline"],["dc.contributor.author","Cosemans, Gwenny"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Raedt, Robrecht"],["dc.contributor.author","Schmidt, Jens"],["dc.contributor.author","De Paepe, Boel"],["dc.contributor.author","De Bleecker, Jan L."],["dc.date.accessioned","2022-04-01T10:02:07Z"],["dc.date.available","2022-04-01T10:02:07Z"],["dc.date.issued","2022"],["dc.date.updated","2022-09-03T13:45:48Z"],["dc.description.abstract","Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration. Osmotic stress participates to DMD pathology and altered levels of osmolyte pathway members have been reported. The goal of this study was to gain insight in osmoregulatory changes in the mdx mouse model by examining the expression of osmolyte pathway members, including taurine transporter (TauT), sodium myo-inositol co-transporter (SMIT), betaine GABA transporter (BGT), and aldose reductase (AR) in the skeletal muscles and diaphragm of mdx mice aged 4, 8, 12, and 26 weeks. Necrosis was most prominent in 12 week-old mdx mice, whereas the amount of regenerated fibers increased until week 26 in the tibialis anterior. TauT protein levels were downregulated in the tibialis anterior and gastrocnemius of 4 to 12 week-old mdx mice, but not in 26 week-old mice, whereas TauT levels in the diaphragm remained significantly lower in 26 week-old mdx mice. In contrast, SMIT protein levels were significantly higher in the muscles of mdx mice when compared to controls. Our study revealed differential regulation of osmolyte pathway members in mdx muscle, which points to their complex involvement in DMD pathogenesis going beyond general osmotic stress responses. These results highlight the potential of osmolyte pathway members as a research interest and future therapeutic target in dystrophinopathy."],["dc.identifier.doi","10.3390/ijms23063251"],["dc.identifier.pii","ijms23063251"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105825"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.title","Description of Osmolyte Pathways in Maturing Mdx Mice Reveals Altered Levels of Taurine and Sodium/Myo-Inositol Co-Transporters"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Neurology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.affiliation","Meyer, Stefanie; 1Department of Neurology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Kaulfuß, Silke; 2Department of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Zechel, Sabrina; 3Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Kummer, Karsten; 1Department of Neurology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Seif Amir Hosseini, Ali; 4Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Ernst, Marielle Sophie; 5Department of Neuroradiology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Schmidt, Jens; 1Department of Neurology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Pauli, Silke; 2Department of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Zschüntzsch, Jana; 1Department of Neurology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.author","Meyer, Stefanie"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Zechel, Sabrina"],["dc.contributor.author","Kummer, Karsten"],["dc.contributor.author","Hosseini, Ali Seif Amir"],["dc.contributor.author","Ernst, Marielle Sophie"],["dc.contributor.author","Schmidt, Jens"],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.date.accessioned","2022-08-04T07:56:56Z"],["dc.date.available","2022-08-04T07:56:56Z"],["dc.date.issued","2022-07-19"],["dc.date.updated","2022-08-02T14:39:17Z"],["dc.description.abstract","Background\r\nBenefits and challenges resulting from advances in genetic diagnostics are two sides of the same coin. Facilitation of a correct and timely diagnosis is paralleled by challenges in interpretation of variants of unknown significance (VUS). Focusing on an individual VUS-re-classification pipeline, this study offers a diagnostic approach for clinically suspected hereditary muscular dystrophy by combining the expertise of an interdisciplinary team.\r\n\r\n\r\nMethods\r\nIn a multi-step approach, a thorough phenotype assessment including clinical examination, laboratory work, muscle MRI and histopathological evaluation of muscle was performed in combination with advanced Next Generation Sequencing (NGS). Different in-silico tools and prediction programs like Alamut, SIFT, Polyphen, MutationTaster and M-Cap as well as 3D- modeling of protein structure and RNA-sequencing were employed to determine clinical significance of the LAMA2 variants.\r\n\r\n\r\nResults\r\nTwo previously unknown sequence alterations in LAMA2 were detected, a missense variant was classified initially according to ACMG guidelines as a VUS (class 3) whereas a second splice site variant was deemed as likely pathogenic (class 4). Pathogenicity of the splice site variant was confirmed by mRNA sequencing and nonsense mediated decay (NMD) was detected. Combination of the detected variants could be associated to the LGMDR23-phenotype based on the MRI matching and literature research.\r\n\r\n\r\nDiscussion\r\nTwo novel variants in LAMA2 associated with LGMDR23-phenotype are described. This study illustrates challenges of the genetic findings due to their VUS classification and elucidates how individualized diagnostic procedure has contributed to the accurate diagnosis in the spectrum of LGMD."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3389/fneur.2022.893605"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112616"],["dc.language.iso","en"],["dc.relation.eissn","1664-2295"],["dc.rights","CC BY 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Evidence of Two Novel LAMA2 Variants in a Patient With Muscular Dystrophy: Facing the Challenges of a Certain Diagnosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]