Gerich, Florian J.

[["dc.bibliographiccitation.firstpage","1016"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neurophysiology"],["dc.bibliographiccitation.lastpage","1032"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Fischer, Marc"],["dc.contributor.author","Reuter, Julia"],["dc.contributor.author","Gerich, Florian J."],["dc.contributor.author","Hildebrandt, Belinda"],["dc.contributor.author","Haegele, Sonja"],["dc.contributor.author","Katschinski, Doerthe"],["dc.contributor.author","Mueller, Michael"],["dc.date.accessioned","2018-11-07T08:33:12Z"],["dc.date.available","2018-11-07T08:33:12Z"],["dc.date.issued","2009"],["dc.description.abstract","Fischer M, Reuter J, Gerich FJ, Hildebrandt B, Hagele S, Katschinski D, Muller M. Enhanced hypoxia susceptibility in hippocampal slices from a mouse model of Rett syndrome. J Neurophysiol 101: 1016-1032, 2009. First published December 10, 2008; doi: 10.1152/jn.91124.2008. Rett syndrome is a neurodevelopmental disorder caused by mutations in the X-chromosomal MECP2 gene encoding for the transcriptional regulator methyl CpG binding protein 2 (MeCP2). Rett patients suffer from episodic respiratory irregularities and reduced arterial oxygen levels. To elucidate whether such intermittent hypoxic episodes induce adaptation/preconditioning of the hypoxia-vulnerable hippocampal network, we analyzed its responses to severe hypoxia in adult Rett mice. The occurrence of hypoxia-induced spreading depression (HSD)-an experimental model for ischemic stroke-was hastened in Mecp2(-/y) males. The extracellular K+ rise during HSD was attenuated in Mecp2(-/y) males and the input resistance of CA1 pyramidal neurons decreased less before HSD onset. CA1 pyramidal neurons were smaller and more densely packed, but the cell swelling during HSD was unaffected. The intrinsic optical signal and the propagation of HSD were similar among the different genotypes. Basal synaptic function was intact, but Mecp2(-/y) males showed reduced paired-pulse facilitation and higher field potential/fiber volley ratios, but no increased seizure susceptibility. Synaptic failure during hypoxia was complete in all genotypes and the final degree of posthypoxic synaptic recovery indistinguishable. Cellular ATP content was normal in Mecp2(-/y) males, but their hematocrit was increased as was HIF-1 alpha expression throughout the brain. This is the first study showing that in Rett syndrome, the susceptibility of telencephalic neuronal networks to hypoxia is increased; the underlying molecular mechanisms apparently involve disturbed K+ channel function. Such an increase in hypoxia susceptibility may potentially contribute to the vulnerability of male Rett patients who are either not viable or severely disabled."],["dc.identifier.doi","10.1152/jn.91124.2008"],["dc.identifier.isi","000263120300047"],["dc.identifier.pmid","19073793"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17518"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","0022-3077"],["dc.title","Enhanced Hypoxia Susceptibility in Hippocampal Slices From a 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"]]

[["dc.bibliographiccitation.firstpage","492"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neurophysiology"],["dc.bibliographiccitation.lastpage","504"],["dc.bibliographiccitation.volume","96"],["dc.contributor.author","Gerich, Florian J."],["dc.contributor.author","Hepp, Sebastian"],["dc.contributor.author","Probst, Irmelin"],["dc.contributor.author","Mueller, Michael"],["dc.date.accessioned","2018-11-07T09:37:08Z"],["dc.date.available","2018-11-07T09:37:08Z"],["dc.date.issued","2006"],["dc.description.abstract","Oxygen withdrawal blocks mitochondrial respiration. In rat hippocampal slices, this triggers a massive depolarization of CA1 neurons and a negative shift of the extracellular DC potential, the characteristic sign of hypoxia-induced spreading depression (HSD). To unveil the contribution of mitochondria to the sensing of hypoxia and the ignition of HSD, we modified mitochondrial function. Mitochondrial uncoupling by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone ( FCCP, 1 mu M) prior to hypoxia hastened the onset and shortened the duration of HSD. Blocking mitochondrial ATP synthesis by oligomycin ( 10 mu g/ml) was without effect. Inhibition of mitochondrial respiration by rotenone (20 mu M), diphenyleneiodonium (25 mu M), or antimycin A (20 mu M) also hastened HSD onset and shortened HSD duration. 3-nitropropionic acid (1 mM) increased HSD duration. Cyanide ( 100 mu M) hastened HSD onset and increased HSD duration. At higher concentrations, cyanide (1 mM), azide (2 mM), and FCCP (10 mu M) triggered SD episodes on their own. Compared with control HSD, the spatial extent of the intrinsic optical signals of cyanide- and azide-induced SDs was more pronounced. Monitoring NADH ( nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) autofluorescence and mitochondrial membrane potential verified the mitochondrial targeting by the drugs used. Except 1 mM cyanide, no treatment reduced cellular ATP levels severely and no correlation was found between ATP, NADH, or FAD levels and the time to HSD onset. Therefore ATP depletion or a cytosolic reducing shift due to NADH/FADH(2) accumulation cannot serve as a general explanation for the hastening of HSD onset on mitochondrial inhibition. Additional redox couples (glutathione) or events downstream of the mitochondrial depolarization need to be considered."],["dc.identifier.doi","10.1152/jn.01015.2005"],["dc.identifier.isi","000238262400045"],["dc.identifier.pmid","16611842"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32768"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","0022-3077"],["dc.title","Mitochondrial inhibition prior to oxygen-withdrawal facilitates the occurrence of hypoxia-induced spreading depression in rat hippocampal slices"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]