Enhanced Hypoxia Susceptibility in Hippocampal Slices From a Mouse Model of Rett Syndrome
Marc Fischer, Julia Reuter, Florian J. Gerich, Belinda Hildebrandt, Sonja Hägele, Dörthe Katschinski, Michael Müller
2009
Journal of Neurophysiology
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
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... oxia-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, 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-1α expression throughout the brain. 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doi:10.1152/jn.91124.2008
pmid:19073793
fatcat:vv4ibzspjffddmcwmeqtnwj7sm