Müller, Michael

[["dc.bibliographiccitation.artnumber","479"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","Rinne, Lena"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Golubiani, Gocha"],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2019-07-09T11:51:15Z"],["dc.date.available","2019-07-09T11:51:15Z"],["dc.date.issued","2019"],["dc.description.abstract","Rett syndrome (RTT), an X chromosome-linked neurodevelopmental disorder affecting almost exclusively females, is associated with various mitochondrial alterations. Mitochondria are swollen, show altered respiratory rates, and their inner membrane is leaking protons. To advance the understanding of these disturbances and clarify their link to redox impairment and oxidative stress, we assessed mitochondrial respiration in defined brain regions and cardiac tissue of male wildtype (WT) and MeCP2-deficient (Mecp2-/y) mice. Also, we quantified for the first time neuronal redox-balance with subcellular resolution in cytosol and mitochondrial matrix. Quantitative roGFP1 redox imaging revealed more oxidized conditions in the cytosol of Mecp2-/y hippocampal neurons than in WT neurons. Furthermore, cytosol and mitochondria of Mecp2-/y neurons showed exaggerated redox-responses to hypoxia and cell-endogenous reactive oxygen species (ROS) formation. Biochemical analyzes exclude disease-related increases in mitochondrial mass in Mecp2-/y hippocampus and cortex. Protein levels of complex I core constituents were slightly lower in Mecp2-/y hippocampus and cortex than in WT; those of complex V were lower in Mecp2-/y cortex. Respiratory supercomplex-formation did not differ among genotypes. Yet, supplied with the complex II substrate succinate, mitochondria of Mecp2-/y cortex and hippocampus consumed more O2 than WT. Furthermore, mitochondria from Mecp2-/y hippocampus and cortex mediated an enhanced oxidative burden. In conclusion, we further advanced the molecular understanding of mitochondrial dysfunction in RTT. Intensified mitochondrial O2 consumption, increased mitochondrial ROS generation and disturbed redox balance in mitochondria and cytosol may represent a causal chain, which provokes dysregulated proteins, oxidative tissue damage, and contributes to neuronal network dysfunction in RTT."],["dc.identifier.doi","10.3389/fphys.2019.00479"],["dc.identifier.pmid","31114506"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16085"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59907"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/12"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Neuronal Redox-Imbalance in Rett Syndrome Affects Mitochondria as Well as Cytosol, and Is Accompanied by Intensified Mitochondrial O2 Consumption and ROS Release"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Janc, Oliwia A."],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T10:14:12Z"],["dc.date.available","2018-09-28T10:14:12Z"],["dc.date.issued","2014"],["dc.description.abstract","Rett syndrome (RS) causes severe cognitive impairment, loss of speech, epilepsy, and breathing disturbances with intermittent hypoxia. Also mitochondria are affected; a subunit of respiratory complex III is dysregulated, the inner mitochondrial membrane is leaking protons, and brain ATP levels seem reduced. Our recent assessment of mitochondrial function in MeCP2 (methyl-CpG-binding protein 2)-deficient mouse (Mecp2 (-) (/y)) hippocampus confirmed early metabolic alterations, an increased oxidative burden, and a more vulnerable cellular redox balance. As these changes may contribute to the manifestation of symptoms and disease progression, we now evaluated whether free radical scavengers are capable of improving neuronal and mitochondrial function in RS. Acute hippocampal slices of adult mice were incubated with the vitamin E derivative Trolox for 3-5 h. In Mecp2 (-) (/y) slices this treatment dampened neuronal hyperexcitability, improved synaptic short-term plasticity, and fully restored synaptic long-term potentiation (LTP). Furthermore, Trolox specifically attenuated the increased hypoxia susceptibility of Mecp2 (-) (/y) slices. Also, the anticonvulsive effects of Trolox were assessed, but the severity of 4-aminopyridine provoked seizure-like discharges was not significantly affected. Adverse side effects of Trolox on mitochondria can be excluded, but clear indications for an improvement of mitochondrial function were not found. Since several ion-channels and neurotransmitter receptors are redox modulated, the mitochondrial alterations and the associated oxidative burden may contribute to the neuronal dysfunction in RS. We confirmed in Mecp2 (-) (/y) hippocampus that Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves the hypoxia tolerance. Therefore, radical scavengers are promising compounds for the treatment of neuronal dysfunction in RS and deserve further detailed evaluation."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.3389/fncel.2014.00056"],["dc.identifier.pmid","24605086"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9944"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15854"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","53"],["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Schnell, Christian"],["dc.contributor.author","Janc, Oliwia A."],["dc.contributor.author","Kempkes, Belinda"],["dc.contributor.author","Araya Callis, Carolina"],["dc.contributor.author","Flügge, Gabriele"],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T10:22:20Z"],["dc.date.available","2018-09-28T10:22:20Z"],["dc.date.issued","2012"],["dc.description.abstract","Chronic stress affects neuronal networks by inducing dendritic retraction, modifying neuronal excitability and plasticity, and modulating glial cells. To elucidate the functional consequences of chronic stress for the hippocampal network, we submitted adult rats to daily restraint stress for 3 weeks (6 h/day). In acute hippocampal tissue slices of stressed rats, basal synaptic function and short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged while long-term potentiation was markedly impaired. The spatiotemporal propagation pattern of hypoxia-induced spreading depression episodes was indistinguishable among control and stress slices. However, the duration of the extracellular direct current potential shift was shortened after stress. Moreover, K(+) fluxes early during hypoxia were more intense, and the postsynaptic recoveries of interstitial K(+) levels and synaptic function were slower. Morphometric analysis of immunohistochemically stained sections suggested hippocampal shrinkage in stressed rats, and the number of cells that are immunoreactive for glial fibrillary acidic protein was increased in the CA1 subfield indicating activation of astrocytes. Western blots showed a marked downregulation of the inwardly rectifying K(+) channel Kir4.1 in stressed rats. Yet, resting membrane potentials, input resistance, and K(+)-induced inward currents in CA1 astrocytes were indistinguishable from controls. These data indicate an intensified interstitial K(+) accumulation during hypoxia in the hippocampus of chronically stressed rats which seems to arise from a reduced interstitial volume fraction rather than impaired glial K(+) buffering. One may speculate that chronic stress aggravates hypoxia-induced pathophysiological processes in the hippocampal network and that this has implications for the ischemic brain."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.3389/fphar.2012.00053"],["dc.identifier.pmid","22470344"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7501"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15856"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1663-9812"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","Restraint Stress Intensifies Interstitial K(+) Accumulation during Severe Hypoxia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","27"],["dc.bibliographiccitation.journal","BMC Biology"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Sargin, Derya"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Agarwal, Amit"],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Hassouna, Imam"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:35Z"],["dc.date.available","2017-09-07T11:46:35Z"],["dc.date.issued","2011"],["dc.description.abstract","BACKGROUND: Erythropoietin (EPO) and its receptor (EPOR) are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply. RESULTS: Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR) in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices. CONCLUSIONS: Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions."],["dc.format.extent","16"],["dc.identifier.doi","10.1186/1741-7007-9-27"],["dc.identifier.gro","3150548"],["dc.identifier.pmid","21527022"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6376"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7322"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2539"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Festerling, Karina"],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2021-04-14T08:26:49Z"],["dc.date.available","2021-04-14T08:26:49Z"],["dc.date.issued","2020"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cells9122539"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17668"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82087"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Overshooting Subcellular Redox-Responses in Rett-Mouse Hippocampus during Neurotransmitter Stimulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Antioxidants"],["dc.bibliographiccitation.volume","11"],["dc.contributor.affiliation","Baroncelli, Laura; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.affiliation","Auel, Stefanie; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.affiliation","Rinne, Lena; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.affiliation","Schuster, Ann-Kathrin; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.affiliation","Brand, Victoria; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.affiliation","Kempkes, Belinda; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.affiliation","Dietrich, Katharina; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.affiliation","Müller, Michael; 1Institut für Neuro- und Sinnesphysiologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; laura.baroncelli@in.cnr.it (L.B.); stefanieauel@yahoo.de (S.A.); lena.rinne@gmx.net (L.R.); ak_schuster@web.de (A.-K.S.); victoriabrand@gmx.de (V.B.); bhildeb2@gwdg.de (B.K.); dietrich.katharina85@gmail.com (K.D.)"],["dc.contributor.author","Baroncelli, Laura"],["dc.contributor.author","Auel, Stefanie"],["dc.contributor.author","Rinne, Lena"],["dc.contributor.author","Schuster, Ann-Kathrin"],["dc.contributor.author","Brand, Victoria"],["dc.contributor.author","Kempkes, Belinda"],["dc.contributor.author","Dietrich, Katharina"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2022-08-04T08:23:31Z"],["dc.date.available","2022-08-04T08:23:31Z"],["dc.date.issued","2022-07-20"],["dc.date.updated","2022-08-03T09:14:27Z"],["dc.description.abstract","Rett syndrome (RTT) is a severe neurodevelopmental disorder that typically arises from spontaneous germline mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2) gene. For the first 6–18 months of life, the development of the mostly female patients appears normal. Subsequently, cognitive impairment, motor disturbances, hand stereotypies, epilepsy, and irregular breathing manifest, with previously learned skills being lost. Early mitochondrial impairment and a systemic oxidative burden are part of the complex pathogenesis, and contribute to disease progression. Accordingly, partial therapeutic merits of redox-stabilizing and antioxidant (AO) treatments were reported in RTT patients and Mecp2-mutant mice. Pursuing these findings, we conducted a full preclinical trial on male and female mice to define the therapeutic value of an orally administered AO cocktail composed of vitamin E, N-acetylcysteine, and α-lipoic acid. AO treatment ameliorated some of the microcephaly-related aspects. Moreover, the reduced growth, lowered blood glucose levels, and the hippocampal synaptic plasticity of Mecp2−/y mice improved. However, the first-time detected intensified oxidative DNA damage in Mecp2-mutant cortex persisted. The behavioral performance, breathing regularity, and life expectancy of Mecp2-mutant mice did not improve upon AO treatment. Long-term-treated Mecp2+/− mice eventually became obese. In conclusion, the AO cocktail ameliorated a subset of symptoms of the complex RTT-related phenotype, thereby further confirming the potential merits of AO-based pharmacotherapies. Yet, it also became evident that long-term AO treatment may lose efficacy and even aggravate the metabolic disturbances in RTT. This emphasizes the importance of a constantly well-balanced redox balance for systemic well-being."],["dc.description.sponsorship","Cluster of Excellence and Deutsche Forschungsgemeinschaft Research Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)"],["dc.description.sponsorship","Umberto Veronesi Foundation"],["dc.description.sponsorship","Georg-August-Universität Göttingen"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/antiox11071406"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112622"],["dc.language.iso","en"],["dc.relation.eissn","2076-3921"],["dc.rights","CC BY 4.0"],["dc.title","Oral Feeding of an Antioxidant Cocktail as a Therapeutic Strategy in a Mouse Model of Rett Syndrome: Merits and Limitations of Long-Term Treatment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","309"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","319"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Gerchen, Martin F."],["dc.contributor.author","Adamcio, Bartosz"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Martin, Sabine"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Radyushkin, Konstantin A."],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Stühmer, Walter"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:44:13Z"],["dc.date.available","2017-09-07T11:44:13Z"],["dc.date.issued","2011"],["dc.description.abstract","KCNN3, encoding the small conductance calcium-activated potassium channel SK3, harbours a polymorphic CAG repeat in the amino-terminal coding region with yet unproven function. Hypothesizing that KCNN3 genotypes do not influence susceptibility to schizophrenia but modify its phenotype, we explored their contribution to specific schizophrenic symptoms. Using the Gottingen Research Association for Schizophrenia (GRAS) data collection of schizophrenic patients (n=1074), we performed a phenotype-based genetic association study (PGAS) of KCNN3. We show that long CAG repeats in the schizophrenic sample are specifically associated with better performance in higher cognitive tasks, comprising the capacity to discriminate, select and execute (p<0.0001). Long repeats reduce SK3 channel function, as we demonstrate by patch-clamping of transfected HEK293 cells. In contrast, modelling the opposite in mice, i.e. KCNN3 overexpression/channel hyperfunction, leads to selective deficits in higher brain functions comparable to those influenced by SK3 conductance in humans. To conclude, KCNN3 genotypes modify cognitive performance, shown here in a large sample of schizophrenic patients. Reduction of SK3 function may constitute a pharmacological target to improve cognition in schizophrenia and other conditions with cognitive impairment."],["dc.identifier.doi","10.1002/emmm.201100135"],["dc.identifier.gro","3142723"],["dc.identifier.isi","000292277600003"],["dc.identifier.pmid","21433290"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8179"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/159"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1757-4676"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A CAG repeat polymorphism of KCNN3 predicts SK3 channel function and cognitive performance in schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2853"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","NUCLEIC ACIDS RESEARCH"],["dc.bibliographiccitation.lastpage","2864"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Schilling, Oliver"],["dc.contributor.author","Langbein, Ines"],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Schmalisch, Matthias H."],["dc.contributor.author","Stülke, Jörg"],["dc.date.accessioned","2019-07-10T08:12:53Z"],["dc.date.available","2019-07-10T08:12:53Z"],["dc.date.issued","2004"],["dc.description.abstract","The Gram-positive soil bacterium Bacillus subtilis transports glucose by the phosphotransferase system. The genes for this system are encoded in the ptsGHI operon. The expression of this operon is controlled at the level of transcript elongation by a protein-dependent riboswitch. In the absence of glucose a transcriptional terminator prevents elongation into the structural genes. In the presence of glucose, the GlcT protein is activated and binds and stabilizes an alternative RNA structure that overlaps the terminator and prevents termination. In this work, we have studied the structural and sequence requirements for the two mutually exclusive RNA structures, the terminator and the RNA antiterminator (the RAT sequence). In both cases, the structure seems to be more important than the actual sequence. The number of paired and unpaired bases in the RAT sequence is essential for recognition by the antiterminator protein GlcT. In contrast, mutations of individual bases are well tolerated as long as the general structure of the RAT is not impaired. The introduction of one additional base in the RAT changed its structure and resulted in complete loss of interaction with GlcT. In contrast, this mutant RAT was efficiently recognized by a different B.subtilis antitermination protein, LicT."],["dc.identifier.fs","28429"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/4114"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61066"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0305-1048"],["dc.relation.issn","1362-4962"],["dc.relation.orgunit","Fakultät für Biologie und Psychologie"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","570"],["dc.title","A protein-dependent riboswitch controlling ptsGHI operon expression in Bacillus subtilis: RNA structure rather than sequence provides interaction specificity."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","3064016"],["dc.bibliographiccitation.journal","Oxidative Medicine and Cellular Longevity"],["dc.bibliographiccitation.volume","2017"],["dc.contributor.author","Bebensee, Dörthe F."],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T09:44:52Z"],["dc.date.available","2018-09-28T09:44:52Z"],["dc.date.issued","2017"],["dc.description.abstract","Rett syndrome (RTT) is a neurodevelopmental disorder with mutations in the MECP2 gene. Mostly girls are affected, and an apparently normal development is followed by cognitive impairment, motor dysfunction, epilepsy, and irregular breathing. Various indications suggest mitochondrial dysfunction. In Rett mice, brain ATP levels are reduced, mitochondria are leaking protons, and respiratory complexes are dysregulated. Furthermore, we found in MeCP2-deficient mouse (Mecp2-/y ) hippocampus an intensified mitochondrial metabolism and ROS generation. We now used emission ratiometric 2-photon imaging to assess mitochondrial morphology, mass, and membrane potential (ΔΨm) in Mecp2-/y hippocampal astrocytes. Cultured astrocytes were labeled with the ΔΨm marker JC-1, and semiautomated analyses yielded the number of mitochondria per cell, their morphology, and ΔΨm. Mecp2-/y astrocytes contained more mitochondria than wild-type (WT) cells and were more oxidized. Mitochondrial size, ΔΨm, and vulnerability to pharmacological challenge did not differ. The antioxidant Trolox opposed the oxidative burden and decreased the mitochondrial mass, thereby dampening the differences among WT and Mecp2-/y astrocytes; mitochondrial size and ΔΨm were not markedly affected. In conclusion, mitochondrial alterations and redox imbalance in RTT also involve astrocytes. Mitochondria are more numerous in Mecp2-/y than in WT astrocytes. As this genotypic difference is abolished by Trolox, it seems linked to the oxidative stress in RTT."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1155/2017/3064016"],["dc.identifier.pmid","28894505"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15846"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1942-0994"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Increased Mitochondrial Mass and Cytosolic Redox Imbalance in Hippocampal Astrocytes of a Mouse Model of Rett Syndrome: Subcellular Changes Revealed by Ratiometric Imaging of JC-1 and roGFP1 Fluorescence"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","818"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Weissbach, Susann"],["dc.contributor.author","Church, Joseph A."],["dc.contributor.author","Schnur, Rhonda"],["dc.contributor.author","Krusen, Martina"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Kühn-Velten, W. Nikolaus"],["dc.contributor.author","Wolf, Annika"],["dc.contributor.author","Huppke, Brenda"],["dc.contributor.author","Millan, Francisca"],["dc.contributor.author","Begtrup, Amber"],["dc.contributor.author","Almusafri, Fatima"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Müller, Michael"],["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","Transcription factor NRF2, encoded by NFE2L2, is the master regulator of defense against stress in mammalian cells. Somatic mutations of NFE2L2 leading to NRF2 accumulation promote cell survival and drug resistance in cancer cells. Here we show that the same mutations as inborn de novo mutations cause an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms. NRF2 accumulation leads to widespread misregulation of gene expression and an imbalance in cytosolic redox balance. The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1038/s41467-017-00932-7"],["dc.identifier.gro","3142218"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14817"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13340"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]