Niebert, Marcus

[["dc.bibliographiccitation.artnumber","385"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Mesuret, Guillaume"],["dc.contributor.author","Dannenberg, Julia"],["dc.contributor.author","Arnoldt, Mauricio"],["dc.contributor.author","Niebert, Marcus"],["dc.date.accessioned","2018-11-07T10:08:36Z"],["dc.date.available","2018-11-07T10:08:36Z"],["dc.date.issued","2016"],["dc.description.abstract","Mutations in methyl-CpG-binding protein 2 (MECP2) gene have been shown to manifest in a neurodevelopmental disorder that is called Rett syndrome. A typical problem that occurs during development is a disturbance of breathing. To address the role of inhibitory neurons, we generated a mouse line that restores MECP2 in inhibitory neurons in the brainstem by crossbreeding a mouse line that expresses the Cre-recombinase (Cre) in inhibitory neurons under the control of the glycine transporter 2 (GIyT2, slc6a5) promotor(GlyT2-Cre) with a mouse line that has a floxed-stop mutation of the Mecp2 gene (Mecp2(stop/y)). Unrestrained whole-body-plethysmography at postnatal day P60 revealed a low respiratory rate and prolonged respiratory pauses in Mecp2(stop/y) mice. In contrast, G/yT2-Cre positive Mecp2(stop/y) mice (Cre; Mecp2(stop/y)) showed greatly improved respiration and were indistinguishable from wild type littermates. These data support the concept that alterations in inhibitory neurons are important for the development of the respiratory phenotype in Rett syndrome."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.3389/fphys.2016.00385"],["dc.identifier.isi","000382923200001"],["dc.identifier.pmid","27672368"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13673"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39494"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.eissn","1664-042X"],["dc.relation.issn","1664-042X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","GlyT2-Dependent Preservation of MECP2-Expression in Inhibitory Neurons Improves Early Respiratory Symptoms but Does Not Rescue Survival in a Mouse Model of Rett Syndrome"],["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","4118"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","4128"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Koch, Uwe R."],["dc.contributor.author","Caley, Alex"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.contributor.author","Mueller, Ulrike"],["dc.contributor.author","Smart, Trevor G."],["dc.contributor.author","Harvey, Robert J."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:37:37Z"],["dc.date.available","2018-11-07T08:37:37Z"],["dc.date.issued","2010"],["dc.description.abstract","Rhythmic breathing movements originate from a dispersed neuronal network in the medulla and pons. Here, we demonstrate that rhythmic activity of this respiratory network is affected by the phosphorylation status of the inhibitory glycine receptor alpha 3 subtype (GlyR alpha 3), which controls glutamatergic and glycinergic neuronal discharges, subject to serotonergic modulation. Serotonin receptor type 1A-specific (5-HTR(1A)-specific) modulation directly induced dephosphorylation of GlyR alpha 3 receptors, which augmented inhibitory glycine-activated chloride currents in HEK293 cells coexpressing 5-HTR(1A) and GlyR alpha 3. The 5-HTR(1A)-GlyR alpha 3 signaling pathway was distinct from opioid receptor signaling and efficiently counteracted opioid-induced depression of breathing and consequential apnea in mice. Paradoxically, this rescue of breathing originated from enhanced glycinergic synaptic inhibition of glutamatergic and glycinergic neurons and caused disinhibition of their target neurons. Together, these effects changed respiratory phase alternations and ensured rhythmic breathing in vivo. GlyR alpha 3-deficient mice had an irregular respiratory rhythm under baseline conditions, and systemic 5-HTR(1A) activation failed to remedy opioid-induced respiratory depression in these mice. Delineation of this 5-HTR(1A)-GlyR alpha 3 signaling pathway offers a mechanistic basis for pharmacological treatment of opioid-induced apnea and other breathing disturbances caused by disorders of inhibitory synaptic transmission, such as hyperekplexia, hypoxia/ischemia, and brainstem infarction."],["dc.identifier.doi","10.1172/JCI43029"],["dc.identifier.isi","000283621800043"],["dc.identifier.pmid","20978350"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6108"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18577"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Clinical Investigation Inc"],["dc.relation.issn","0021-9738"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serotonin receptor 1A-modulated phosphorylation of glycine receptor alpha 3 controls breathing in mice"],["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","173"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","191"],["dc.bibliographiccitation.volume","597"],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Oke, Yoshihiko"],["dc.contributor.author","Mesuret, Guillaume"],["dc.contributor.author","Latal, A. Tobias"],["dc.contributor.author","Fortuna, Michal G."],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.contributor.author","Fischer, Julia"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.date.accessioned","2019-07-30T07:09:26Z"],["dc.date.available","2019-07-30T07:09:26Z"],["dc.date.issued","2019"],["dc.description.abstract","Newborn mice produce ultrasonic vocalization to communicate with their mother. The neuronal glycine transporter (GlyT2) is required for efficient loading of synaptic vesicles in glycinergic neurons. Mice lacking GlyT2 develop a phenotype that resembles human hyperekplexia and the mice die in the second postnatal week. In the present study, we show that GlyT2-knockout mice do not acquire adult ultrasonic vocalization-associated breathing patterns. Despite the strong impairment of glycinergic inhibition, they can produce sufficient expiratory airflow to produce ultrasonic vocalization. Because mouse ultrasonic vocalization is a valuable read-out in translational research, these data are highly relevant for a broad range of research fields."],["dc.identifier.doi","10.1113/JP276976"],["dc.identifier.pmid","30296333"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62159"],["dc.language.iso","en"],["dc.relation.eissn","1469-7793"],["dc.relation.issn","0022-3751"],["dc.relation.issn","1469-7793"],["dc.title","The postnatal development of ultrasonic vocalization-associated breathing is altered in glycine transporter 2-deficient mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","28"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.lastpage","7"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Bischoff, Anne M."],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Manzke, Till"],["dc.date.accessioned","2019-07-09T11:45:09Z"],["dc.date.available","2019-07-09T11:45:09Z"],["dc.date.issued","2018"],["dc.description.abstract","Mutations in the transcription factor methyl-CpG-binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome (RTT). Besides many other neurological problems, RTT patients show irregular breathing with recurrent apneas or breath-holdings. MeCP2-deficient mice, which recapitulate this breathing phenotype, show a dysregulated, persistent expression of G-protein-coupled serotonin receptor 5-ht5b (Htr5b) in the brainstem. To investigate whether the persistence of 5-ht5b expression is contributing to the respiratory phenotype, we crossbred MeCP2-deficient mice with 5-ht5b-deficient mice to generate double knockout mice (Mecp2-/y ;Htr5b-/-). To compare respiration between wild type (WT), Mecp2-/y and Mecp2-/y ;Htr5b-/- mice, we used unrestrained whole-body plethysmography. While the breathing of MeCP2-deficient male mice (Mecp2-/y ) at postnatal day 40 is characterized by a slow breathing rate and the occurrence of prolonged respiratory pauses, we found that in MeCP2-deficient mice, which also lacked the 5-ht5b receptor, the breathing rate and the number of pauses were indistinguishable from WT mice. To test for a potential mechanism, we also analyzed if the known coupling of 5-ht5b receptors to Gi proteins is altering second messenger signaling. Tissue cAMP levels in the medulla of Mecp2-/y mice were decreased as compared to WT mice. In contrast, cAMP levels in Mecp2-/y ;Htr5b-/- mice were indistinguishable from WT mice. Taken together, our data points towards a role of 5-ht5b receptors within the complex breathing phenotype of MeCP2-deficient mice."],["dc.identifier.doi","10.3389/fnmol.2018.00028"],["dc.identifier.pmid","29515365"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15043"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59167"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5099"],["dc.relation.issn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Persistent Expression of Serotonin Receptor 5b Alters Breathing Behavior in Male MeCP2 Knockout Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","43"],["dc.bibliographiccitation.journal","Respiratory Physiology & Neurobiology"],["dc.bibliographiccitation.lastpage","47"],["dc.bibliographiccitation.volume","248"],["dc.contributor.author","Mesuret, Guillaume"],["dc.contributor.author","Dannenberg, Julia"],["dc.contributor.author","Arnoldt, Mauricio"],["dc.contributor.author","Grützner, Anja-Annett"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Hülsmann, Swen"],["dc.date.accessioned","2020-12-10T15:21:04Z"],["dc.date.available","2020-12-10T15:21:04Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.resp.2017.11.011"],["dc.identifier.issn","1569-9048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72907"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Breathing disturbances in a model of Rett syndrome: A potential involvement of the glycine receptor α3 subunit?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","61"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Niebert, Sabine"],["dc.contributor.author","Renner, Ute"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Niebert, Marcus"],["dc.date.accessioned","2018-11-07T10:26:17Z"],["dc.date.available","2018-11-07T10:26:17Z"],["dc.date.issued","2017"],["dc.description.abstract","Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT). Although alteration in serotonin levels have been reported in RTT patients, the molecular mechanisms underlying these defects are not well understood. Therefore, we chose to investigate the serotonergic system in hippocampus and brainstem of male Mecp2(-/y) knock-out mice in the B6.129P2(C)-Mecp2(tm1.1Bird) mouse model of RTT. The serotonergic system in mouse is comprised of 16 genes, whose mRNA expression profile was analyzed by quantitative RT-PCR. Mecp2(-/y) mice are an established animal model for RTT displaying most of the cognitive and physical impairments of human patients and the selected areas receive significant modulation through serotonin. Using anatomically and functional characterized areas, we found regionspecific differential expression between wild type and Mecp2(-/y) mice at post-natal day 40. In brainstem, we found five genes to be dysregulated, while in hippocampus, two genes were dysregulated. The one gene dysregulated in both brain regions was dopamine decarboxylase, but of special interest is the serotonin receptor 5b (5-ht5b), which showed 75-fold dysregulation in brainstem of Mecp2(-/y) mice. This dysregulation was not due to upregulation, but due to failure of down-regulation in Mecp2(-/y) mice during development. Detailed analysis of 5-ht5b revealed a receptor that localizes to endosomes and interacts with G(alpha i) proteins."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.3389/fnmol.2017.00061"],["dc.identifier.isi","000395685700001"],["dc.identifier.pmid","28337123"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14369"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43005"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Frontiers Media Sa"],["dc.relation.issn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b"],["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"]]