Mironov, Sergej L.

[["dc.bibliographiccitation.firstpage","2473"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","2485"],["dc.bibliographiccitation.volume","587"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Skorova, Ekaterina Y."],["dc.contributor.author","Hartelt, N."],["dc.contributor.author","Mironova, Lidia A."],["dc.contributor.author","Hasan, Mazahir T."],["dc.contributor.author","Kuegler, Sebastian"],["dc.date.accessioned","2018-11-07T08:29:29Z"],["dc.date.available","2018-11-07T08:29:29Z"],["dc.date.issued","2009"],["dc.description.abstract","Rett syndrome caused by MeCP2 mutations is a devastating neurodevelopmental disorder accompanied by severe breathing irregularities. Using transduction of organotypic slices from model MeCP2-/y mice with neuron-specific calcium sensor protein D3cpv, we examined the slow calcium buffering in neurons in pre-Botzinger complex (preBotC), a component of the complex respiratory network. Examination of wild-type (WT) and MeCP2 null mice showed clear differences in the spatial organisations of neurons in preBotC and also in the disturbances in calcium homeostasis in mutant mice during early postnatal development. Deregulated calcium buffering in MeCP2-/y neurons was indicated by increased amplitude and kinetics of depolarisation-induced calcium transients. Both effects were related to an insufficient calcium uptake into the endoplasmic reticulum that was restored after pretreatment with brain-derived neurotrophic factor (BNDF). Conversely, the inhibition of BDNF signalling in WT neurons produced disturbances similar to those observed in MeCP2-/y mice. Brief hypoxia and calcium release from internal stores induced global calcium increases, after which the processes of many MeCP2-/y neurons were retracted, an effect that was also corrected by pretreatment with BDNF. The data obtained point to a tight connection between calcium homeostasis and long-term changes in neuronal connectivity. We therefore propose that calcium-dependent retraction of neurites in preBotC neurons can cause remodelling of the neuronal network during development and set up the conditions for appearance of breathing irregularities in Rett model mice."],["dc.identifier.doi","10.1113/jphysiol.2009.169805"],["dc.identifier.isi","000266492200010"],["dc.identifier.pmid","19359374"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16662"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","0022-3751"],["dc.title","Remodelling of the respiratory network in a mouse model of Rett syndrome depends on brain-derived neurotrophic factor regulated slow calcium buffering"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","425"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular and Cellular Neuroscience"],["dc.bibliographiccitation.lastpage","431"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Hartelt, N."],["dc.contributor.author","Skorova, Ekaterina Y."],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Suhr, M."],["dc.contributor.author","Mironova, L."],["dc.contributor.author","Kuegler, Sebastian"],["dc.contributor.author","Mironov, Sergej L."],["dc.date.accessioned","2018-11-07T11:17:53Z"],["dc.date.available","2018-11-07T11:17:53Z"],["dc.date.issued","2008"],["dc.description.abstract","Topology of neuronal networks contributes to their functioning but the structure-function relationships are not yet understood. In order to reveal the spatial organisation of the respiratory network, we expressed enhanced green fluorescent proteins in neurons in brainstem slices containing the respiratory kernel (pre-Botzinger complex). The expression was neuron specific due to use of adeno-associated viral vector driving transgene expression from synapsin I promoter. Both neuronal cell bodies and their dendrites were labelled with high efficacy. This labelling allowed for enhanced spatial resolution as compared to conventional calcium-sensitive dyes. Neurons occupied about 10% of tissue volume and formed an interconnected network. Using custom-developed software, we quantified the network structure that had a modular structure consisting of clusters having transverse (dorsoventral) orientation. They contained in average seven neurons and connections between the cells in different clusters were less frequent. This novel in situ imaging technique is promising to gain new knowledge about the fine structure and function of neuronal networks in living slice preparations. (c) 2007 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.mcn.2007.10.011"],["dc.identifier.isi","000253928500001"],["dc.identifier.pmid","18203620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54917"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1044-7431"],["dc.title","Imaging of respiratory network topology in living brainstem slices"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","47"],["dc.bibliographiccitation.journal","Molecular and Cellular Neuroscience"],["dc.bibliographiccitation.lastpage","56"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Toloe, J."],["dc.contributor.author","Mollajew, R."],["dc.contributor.author","Kuegler, Sebastian"],["dc.contributor.author","Mironov, Sergej L."],["dc.date.accessioned","2018-11-07T09:42:51Z"],["dc.date.available","2018-11-07T09:42:51Z"],["dc.date.issued","2014"],["dc.description.abstract","Understanding metabolic control of neuronal function requires detailed knowledge of ATP handling in living neurons. We imaged ATP in organotypic hippocampal slices using genetically encoded sensor Ateam 1.03 modified to selectively transduce neurons in the tissue. ATP imaging indicated distinct differences in ATP production and consumption in dentate gyrus and cornu ammonis (CA) areas. Removal of extracellular Mg2+ from the bath evoked epileptiform-like activity that was accompanied by ATP decline from 2-3 to 1-2 mM. The slices fully recovered from treatment and showed persistent spontaneous activity. Neuronal discharges were followed by transient ATP changes and periodic activation of ATP-sensitive K+ (K-ATP) channels. The biggest ATP decreases during epileptiform-like episodes of activity were observed in CA1 and CA3 neurons. Examination of neurons from the Rett model mice MeCP2(-/y) showed that seizure-like activity had earlier onset and subsequent spontaneous activity demonstrated more frequent discharges. Hippocampal MeCP2(-/y) neurons had higher resting ATP levels and showed bigger ATP decreases during epileptiform-like activity. More intense ATP turnover in MeCP2(-/y) neurons may result from necessity to maintain hippocampal function in Rett syndrome. Elevated ATP may make, in turn, Rett hippocampus more prone to epilepsy due to inadequate activity of K-ATP channels. (C) 2014 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.mcn.2013.12.008"],["dc.identifier.isi","000336338400005"],["dc.identifier.pmid","24394521"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34052"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1095-9327"],["dc.relation.issn","1044-7431"],["dc.title","Metabolic differences in hippocampal 'Ratt' neurons revealed by ATP imaging"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","29"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Skorova, Ekaterina Y."],["dc.contributor.author","Taschenberger, Grit"],["dc.contributor.author","Hartelt, N."],["dc.contributor.author","Nikolaev, V. O."],["dc.contributor.author","Lohse, Martin J."],["dc.contributor.author","Kuegler, Sebastian"],["dc.date.accessioned","2018-11-07T08:31:34Z"],["dc.date.available","2018-11-07T08:31:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca(2+) levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before. Results: Using a strictly neuron-restricted promoter we virally transduced neurons in the organotypic brainstem slices which contained pre-Botzinger complex, constituting the rhythm-generating part of the respiratory network. Fluorescent cAMP sensor Epac1-camps was expressed both in neuronal cell bodies and neurites, allowing us to measure intracellular distribution of cAMP, its absolute levels and time-dependent changes in response to physiological stimuli. We recorded [cAMP](i) changes in the micromolar range after modulation of adenylate cyclase, inhibition of phosphodiesterase and activation of G-protein-coupled metabotropic receptors. [cAMP](i) levels increased after membrane depolarisation and release of Ca(2+) from internal stores. The effects developed slowly and reached their maximum after transient [Ca(2+)](i) elevations subsided. Ca(2+)-dependent [cAMP](i) transients were suppressed after blockade of adenylate cyclase with 0.1 mM adenylate cyclase inhibitor 2'5'-dideoxyadenosine and potentiated after inhibiting phosphodiesterase with isobutylmethylxanthine and rolipram. During paired stimulations, the second depolarisation and Ca(2+) release evoked bigger cAMP responses. These effects were abolished after inhibition of protein kinase A with H-89 pointing to the important role of phosphorylation of calcium channels in the potentiation of [cAMP](i) transients. Conclusion: We constructed and characterized a neuron-specific cAMP probe based on Epac1-camps. Using viral gene transfer we showed its efficient expression in organotypic brainstem preparations. Strong fluorescence, resistance to photobleaching and possibility of direct estimation of [cAMP] levels using dual wavelength measurements make the probe useful in studies of neurons and the mechanisms of their plasticity. Epac1-camps was applied to examine the crosstalk between Ca(2+) and cAMP signalling and revealed a synergism of actions of these two second messengers."],["dc.identifier.doi","10.1186/1471-2202-10-29"],["dc.identifier.isi","000265852000001"],["dc.identifier.pmid","19327133"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17151"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1471-2202"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Imaging cytoplasmic cAMP in mouse brainstem neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","869"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neuropharmacology"],["dc.bibliographiccitation.lastpage","877"],["dc.bibliographiccitation.volume","60"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Skorova, Ekaterina Y."],["dc.contributor.author","Kuegler, Sebastian"],["dc.date.accessioned","2018-11-07T08:56:50Z"],["dc.date.available","2018-11-07T08:56:50Z"],["dc.date.issued","2011"],["dc.description.abstract","Rett Syndrome (RTT) is a neurodevelopmental disease thought to be caused by deficits in synaptogenesis and neuronal circuitry. cAMP is one of the key factors for neuronal outgrowth, plasticity and regeneration. We examined its homeostasis in RTT during early postnatal development of the essential part of the respiratory network, pre-Botzinger complex. Using targeted expression of Epac1-camps sensor in neurons we quantified CAMP levels and their fluctuations in MeCP2-/y mice, an established model of RTT. Resting cAMP levels in the mutant were smaller than in the wild-type. cAMP transients elicited by depolarisation and stimulation of adenylate cyclase had also smaller amplitudes and faster time-courses. The anomalies in MeCP2 -/y mice were removed after inhibition of phosphodiesterase PDE4 with rolipram. Brief CAMP elevations triggered elongation of neuronal processes that was significantly bigger in the wild-type. The effects were observed after inhibition of protein kinase A and mimicked by activation of a guanine nucleotide exchange factor. Epac, with 8-(4-Chlorophenylthio)-2'-O-methyl-adenosine-3',5'-cyclic monophosphate (8-pCPT). The agonist reinforced bursting in preBotC neurons in the mutant and converted it to the wild-type. All actions of 8-pCPT were not reproduced by its non-active analogue and abolished by Epac signalling inhibitor Brefeldin A. We propose that disturbances in cAMP homeostasis in MeCP2 -/y mice can lead to inadequate Epac signalling. Concomitant defective development of respiratory circuits may be responsible for irregular breathing activity in RTT. (C) 2011 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neuropharm.2011.01.002"],["dc.identifier.isi","000289133200006"],["dc.identifier.pmid","21232545"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23247"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0028-3908"],["dc.title","Epac-mediated cAMP-signalling in the mouse model of Rett Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]