{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:01:29Z","timestamp":1784199689452,"version":"3.55.0"},"reference-count":101,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CNMPB"],"award-info":[{"award-number":["CNMPB"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Land Niedersachsen &amp; Universit\u00e4tsmedizin G\u00f6ttingen","award":["INST 1525\/14-1 FUGG"],"award-info":[{"award-number":["INST 1525\/14-1 FUGG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Rett syndrome (RTT) is a neurodevelopmental disorder associated with disturbed neuronal responsiveness and impaired neuronal network function. Furthermore, mitochondrial alterations and a weakened cellular redox-homeostasis are considered part of the complex pathogenesis. So far, overshooting redox-responses of MeCP2-deficient neurons were observed during oxidant-mediated stress, hypoxia and mitochondrial inhibition. To further clarify the relevance of the fragile redox-balance for the neuronal (dys)function in RTT, we addressed more physiological stimuli and quantified the subcellular redox responses to neurotransmitter-stimulation. The roGFP redox sensor was expressed in either the cytosol or the mitochondrial matrix of cultured mouse hippocampal neurons, and the responses to transient stimulation by glutamate, serotonin, dopamine and norepinephrine were characterized. Each neurotransmitter evoked more intense oxidizing responses in the cytosol of MeCP2-deficient than in wildtype neurons. In the mitochondrial matrix the neurotransmitter-evoked oxidizing changes were more moderate and more uniform among genotypes. This identifies the cytosol as an important reactive oxygen species (ROS) source and as less stably redox buffered. Fura-2 imaging and extracellular Ca2+ withdrawal confirmed cytosolic Ca2+ transients as a contributing factor of neurotransmitter-induced redox responses and their potentiation in the cytosol of MeCP2-deficient neurons. Chemical uncoupling demonstrated the involvement of mitochondria. Nevertheless, cytosolic NADPH- and xanthine oxidases interact to play the leading role in the neurotransmitter-mediated oxidizing responses. As exaggerated redox-responses were already evident in neonatal MeCP2-deficient neurons, they may contribute remarkably to the altered neuronal network performance and the disturbed neuronal signaling, which are among the hallmarks of RTT.<\/jats:p>","DOI":"10.3390\/cells9122539","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T20:50:22Z","timestamp":1606251022000},"page":"2539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Overshooting Subcellular Redox-Responses in Rett-Mouse Hippocampus during Neurotransmitter Stimulation"],"prefix":"10.3390","volume":"9","author":[{"given":"Karina","family":"Festerling","sequence":"first","affiliation":[{"name":"Zentrum Physiologie und Pathophysiologie, Institut f\u00fcr Neuro- und Sinnesphysiologie, Georg-August-Universit\u00e4t G\u00f6ttingen, Universit\u00e4tsmedizin G\u00f6ttingen, Humboldtallee 23, D-37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Can","sequence":"additional","affiliation":[{"name":"Zentrum Physiologie und Pathophysiologie, Institut f\u00fcr Neuro- und Sinnesphysiologie, Georg-August-Universit\u00e4t G\u00f6ttingen, Universit\u00e4tsmedizin G\u00f6ttingen, Humboldtallee 23, D-37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"K\u00fcgler","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Neurologie, Georg-August-Universit\u00e4t G\u00f6ttingen, Universit\u00e4tsmedizin G\u00f6ttingen, Robert-Koch Stra\u00dfe 40, D-37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Zentrum Physiologie und Pathophysiologie, Institut f\u00fcr Neuro- und Sinnesphysiologie, Georg-August-Universit\u00e4t G\u00f6ttingen, Universit\u00e4tsmedizin G\u00f6ttingen, Humboldtallee 23, D-37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1651-2227.1985.tb10993.x","article-title":"Rett\u2019s syndrome: Prevalence and impact on progressive severe mental retardation in girls","volume":"74","author":"Hagberg","year":"1985","journal-title":"Acta Paediatr. 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