Manzke, Till U.

[["dc.bibliographiccitation.firstpage","1276"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","1291"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Shevtsova, Natalia A."],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Molkov, Yaroslav I."],["dc.contributor.author","Bischoff, Anne M."],["dc.contributor.author","Smith, Jeffrey C."],["dc.contributor.author","Rybak, Ilya A."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:50:56Z"],["dc.date.available","2018-11-07T08:50:56Z"],["dc.date.issued","2011"],["dc.description.abstract","Brainstem respiratory neurons express the glycine a3 receptor (Glya3R), which is a target of modulation by several serotonin (5-HT) receptor agonists. Application of the 5-HT1A receptor (5-HT1AR) agonist 8-OH-DPAT was shown (i) to depress cellular cAMP, leading to dephosphorylation of Glya3R and augmentation of postsynaptic inhibition of neurons expressing Glya3R (Manzke , 2010) and (ii) to hyperpolarize respiratory neurons through 5-HT-activated potassium channels. These processes counteract opioid-induced depression and restore breathing from apnoeas often accompanying pharmacotherapy of pain. The effect is postulated to rely on the enhanced Glya3R-mediated inhibition of inhibitory neurons causing disinhibition of their target neurons. To evaluate this proposal and investigate the neural mechanisms involved, an established computational model of the brainstem respiratory network (Smith , 2007), was extended by (i) incorporating distinct subpopulations of inhibitory neurons (glycinergic and GABAergic) and their synaptic interconnections within the Botzinger and pre-Botzinger complexes and (ii) assigning the 5-HT1AR-Glya3R complex to some of these inhibitory neuron types in the network. The modified model was used to simulate the effects of 8-OH-DPAT on the respiratory pattern and was able to realistically reproduce a number of experimentally observed responses, including the shift in the onset of post-inspiratory activity to inspiration and conversion of the eupnoeic three-phase rhythmic pattern into a two-phase pattern lacking the post-inspiratory phase. The model shows how 5-HT1AR activation can produce a disinhibition of inspiratory neurons, leading to the recovery of respiratory rhythm from opioid-induced apnoeas."],["dc.identifier.doi","10.1111/j.1460-9568.2011.07825.x"],["dc.identifier.isi","000297014000011"],["dc.identifier.pmid","21899601"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21810"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0953-816X"],["dc.title","Computational modelling of 5-HT receptor-mediated reorganization of the brainstem respiratory network"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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.journal","The FASEB Journal"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Shevtsova, Natalia A."],["dc.contributor.author","Bischoff, Anne M."],["dc.contributor.author","Molkov, Yaroslav I."],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Rybak, Ilya A."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:57:49Z"],["dc.date.available","2018-11-07T08:57:49Z"],["dc.date.issued","2011"],["dc.identifier.isi","000310708403961"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23492"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.publisher.place","Bethesda"],["dc.relation.conference","Experimental Biology Meeting 2011"],["dc.relation.eventlocation","Washington, DC"],["dc.relation.issn","0892-6638"],["dc.title","Computational Modeling of Serotonin-Evoked Reorganization of the Brain Stem Respiratory Network"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]