{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T15:30:34Z","timestamp":1764603034801},"reference-count":79,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:p>Rett syndrome (RTT) patients suffer from respiratory arrhythmias with frequent apneas causing intermittent hypoxia. In a RTT mouse model (methyl-CpG-binding protein 2-deficient mice; Mecp2<jats:sup>\u2212\/ y<\/jats:sup>) we recently discovered an enhanced hippocampal susceptibility to hypoxia and hypoxia-induced spreading depression (HSD). In the present study we investigated whether this also applies to infant Mecp2<jats:sup>\u2212\/ y<\/jats:sup>brain stem, which could become life-threatening due to failure of cardiorespiratory control. HSD most reliably occurred in the nucleus of the solitary tract (NTS) and the spinal trigeminal nucleus (Sp5). HSD susceptibility of the Mecp2<jats:sup>\u2212\/ y<\/jats:sup>NTS and Sp5 was increased on 8 mM K<jats:sup>+<\/jats:sup>-mediated conditioning. 5-HT<jats:sub>1A<\/jats:sub>receptor stimulation with 8-hydroxy-2-(di-propylamino)tetralin (8-OH-DPAT) postponed HSD by up to 40%, mediating genotype-independent protection. The deleterious impact of HSD on in vitro respiration became obvious in rhythmically active slices, where HSD propagation into the pre-B\u00f6tzinger complex (pre-B\u00f6tC) immediately arrested the respiratory rhythm. Compared with wild-type, the Mecp2<jats:sup>\u2212\/ y<\/jats:sup>pre-B\u00f6tC was invaded less frequently by HSD, but if so, HSD occurred earlier. On reoxygenation, in vitro rhythms reappeared with increased frequency, which was less pronounced in Mecp2<jats:sup>\u2212\/ y<\/jats:sup>slices. 8-OH-DPAT increased respiratory frequency but failed to postpone HSD in the pre-B\u00f6tC. Repetitive hypoxia facilitated posthypoxic recovery only if HSD occurred. In 57% of Mecp2<jats:sup>\u2212\/ y<\/jats:sup>slices, however, HSD spared the pre-B\u00f6tC. Although this occasionally promoted residual hypoxic respiratory activity (\u201cgasping\u201d), it also prolonged the posthypoxic recovery, and thus the absence of central inspiratory drive, which in vivo would lengthen respiratory arrest. In view of the breathing disorders in RTTs, the increased hypoxia susceptibility of MeCP2-deficient brain stem potentially contributes to life-threatening disturbances of cardiorespiratory control.<\/jats:p>","DOI":"10.1152\/jn.00822.2010","type":"journal-article","created":{"date-parts":[[2011,4,7]],"date-time":"2011-04-07T05:00:44Z","timestamp":1302152444000},"page":"3067-3079","source":"Crossref","is-referenced-by-count":16,"title":["Altered responses of MeCP2-deficient mouse brain stem to severe hypoxia"],"prefix":"10.1152","volume":"105","author":[{"given":"Miriam","family":"Kron","sequence":"first","affiliation":[{"name":"Deutsche Forschungsgemeinschaft Research Center for Molecular Physiology of the Brain, Zentrum f\u00fcr Physiologie und Pathophysiologie, Abteilung Neuro- und Sinnesphysiologie, and"},{"name":"Bernstein Center for Computational Neuroscience, Georg-August-Universit\u00e4t G\u00f6ttingen, G\u00f6ttingen, 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