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Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome

Turovsky, E; Karagiannis, A; Abdala, AP; Gourine, AV; (2015) Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome. Journal of Physiology , 593 (14) pp. 3159-3168. 10.1113/JP270369. Green open access

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Abstract

Rett syndrome is a prototypical neurological disorder characterised by abnormal breathing pattern and reduced ventilatory CO2 sensitivity. Medullary astrocytes are a crucial component of central CO2 /pH chemosensitivity. This study tested the hypotheses that methyl-CpG-binding protein 2 (MeCP2) deficient medullary astrocytes are (i) unable to produce/release appropriate amounts of lactate, and/or (ii) unable to sense changes in PCO2/[H(+) ]. We found no differences in tonic or hypoxia-induced release of lactate from the ventral surface of the medulla oblongata or cerebral cortex between MeCP2-knockout and wild-type mice. Respiratory acidosis triggered robust [Ca(2+) ]i responses in wild-type astrocytes residing near the ventral surface of the medulla oblongata. CO2 -induced [Ca(2+) ]i responses in astrocytes were dramatically reduced in conditions of MeCP2 deficiency. These data suggest that (i) 'metabolic' function of astrocytes in releasing lactate into the extracellular space is not affected by MeCP2 deficiency, and (ii) MeCP2 deficiency impairs the ability of medullary astrocytes to sense changes in PCO2/[H(+) ].

Type: Article
Title: Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/JP270369
Publisher version: http://dx.doi.org/10.1113/JP270369
Language: English
Additional information: © 2015 The Authors The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1471756
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