Kempkes, Belinda

[["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.journal","Acta Physiologica"],["dc.bibliographiccitation.volume","213"],["dc.contributor.author","Janc, O."],["dc.contributor.author","Kempkes, B."],["dc.contributor.author","Mueller, M."],["dc.date.accessioned","2018-11-07T09:59:53Z"],["dc.date.available","2018-11-07T09:59:53Z"],["dc.date.issued","2015"],["dc.format.extent","174"],["dc.identifier.isi","000362554200391"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37691"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1748-1716"],["dc.relation.issn","1748-1708"],["dc.title","Systemic radical scavenger treatment of a mouse model of Rett syndrom"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","102"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","114"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Grosser, Emanuel"],["dc.contributor.author","Hirt, Ursula"],["dc.contributor.author","Janc, Oliwia A."],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","Fischer, Marc"],["dc.contributor.author","Kempkes, Belinda"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Manzke, Till U."],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T10:18:29Z"],["dc.date.available","2018-09-28T10:18:29Z"],["dc.date.issued","2012"],["dc.description.abstract","Rett syndrome is an X chromosome-linked neurodevelopmental disorder associated with cognitive impairment, motor dysfunction and breathing irregularities causing intermittent hypoxia. Evidence for impaired mitochondrial function is also accumulating. A subunit of complex III is among the potentially dys-regulated genes, the inner mitochondrial membrane is leaking protons, brain ATP levels seem reduced, and Rett patient blood samples confirm increased oxidative damage. We therefore screened for mitochondrial dysfunction and impaired redox balance. In hippocampal slices of a Rett mouse model (Mecp2(-/y)) we detected an increased FAD/NADH baseline-ratio indicating intensified oxidization. Cyanide-induced anoxia caused similar decreases in FAD/NADH ratio and mitochondrial membrane potential in both genotypes, but Mecp2(-/y) mitochondria seemed less polarized. Quantifying cytosolic redox balance with the genetically-encoded optical probe roGFP1 confirmed more oxidized baseline conditions, a more vulnerable redox-balance, and more intense responses of Mecp2(-/y) hippocampus to oxidative challenge and mitochondrial impairment. Trolox treatment improved the redox baseline of Mecp2(-/y) hippocampus and dampened its exaggerated responses to oxidative challenge. Microarray analysis of the hippocampal CA1 subfield did not detect alterations of key mitochondrial enzymes or scavenging systems. Yet, quantitative PCR confirmed a moderate upregulation of superoxide dismutase 1 in Mecp2(-/y) hippocampus, which might be a compensatory response to the increased oxidative burden. Since several receptors and ion-channels are redox-modulated, the mitochondrial and redox changes which already manifest in neonates could contribute to the hyperexcitability and diminished synaptic plasticity in MeCP2 deficiency. Therefore, targeting cellular redox balance might qualify as a potential pharmacotherapeutic approach to improve neuronal network function in Rett syndrome."],["dc.identifier.doi","10.1016/j.nbd.2012.06.007"],["dc.identifier.pmid","22750529"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15855"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1095-953X"],["dc.title","Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","266"],["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Janc, Oliwia A."],["dc.contributor.author","Hüser, Marc A."],["dc.contributor.author","Dietrich, Katharina"],["dc.contributor.author","Kempkes, Belinda"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T09:49:07Z"],["dc.date.available","2018-09-28T09:49:07Z"],["dc.date.issued","2016"],["dc.description.abstract","Rett syndrome (RTT) is a severe neurodevelopmental disorder typically arising from spontaneous mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2) gene. The almost exclusively female Rett patients show an apparently normal development during their first 6-18 months of life. Subsequently, cognitive- and motor-impairment, hand stereotypies, loss of learned skills, epilepsy and irregular breathing manifest. Early mitochondrial impairment and oxidative challenge are considered to facilitate disease progression. Along this line, we recently confirmed in vitro that acute treatment with the vitamin E-derivative Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, ameliorates cellular redox balance and improves hypoxia tolerance in male MeCP2-deficient (Mecp2-/y ) mouse hippocampus. Pursuing these promising findings, we performed a preclinical study to define the merit of systemic Trolox administration. Blinded, placebo-controlled in vivo treatment of male mice started at postnatal day (PD) 10-11 and continued for ~40 days. Compounds (vehicle only, 10 mg/kg or 40 mg/kg Trolox) were injected intraperitoneally every 48 h. Detailed phenotyping revealed that in Mecp2-/y mice, blood glucose levels, lipid peroxidation, synaptic short-term plasticity, hypoxia tolerance and certain forms of environmental exploration were improved by Trolox. Yet, body weight and size, motor function and the rate and regularity of breathing did not improve. In conclusion, in vivo Trolox treatment partially ameliorated a subset of symptoms of the complex Rett phenotype, thereby confirming a partial merit of the vitamin E-derivative based pharmacotherapy. Yet, it also became evident that frequent animal handling and the route of drug administration are critical issues to be optimized in future trials."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.3389/fncel.2016.00266"],["dc.identifier.pmid","27895554"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13968"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15847"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Systemic Radical Scavenger Treatment of a Mouse Model of Rett Syndrome: Merits and Limitations of the Vitamin E Derivative Trolox"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]