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Astrocytic mitochondrial membrane hyperpolarization following extended oxygen and glucose deprivation

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Norris, Christopher Mark, Korenić, Andrej, Boltze, Johannes, Deten, Alexander, Peters, Myriam, Andjus, Pavle and Radenović, Lidija (2014) Astrocytic mitochondrial membrane hyperpolarization following extended oxygen and glucose deprivation. PLoS One, 9 (2). e90697. doi:10.1371/journal.pone.0090697 ISSN 1932-6203.

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Official URL: http://dx.doi.org/10.1371/journal.pone.0090697

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Abstract

Astrocytes can tolerate longer periods of oxygen and glucose deprivation (OGD) as compared to neurons. The reasons for this reduced vulnerability are not well understood. Particularly, changes in mitochondrial membrane potential (Δψm) in astrocytes, an indicator of the cellular redox state, have not been investigated during reperfusion after extended OGD exposure. Here, we subjected primary mouse astrocytes to glucose deprivation (GD), OGD and combinations of both conditions varying in duration and sequence. Changes in Δψm, visualized by change in the fluorescence of JC-1, were investigated within one hour after reconstitution of oxygen and glucose supply, intended to model in vivo reperfusion. In all experiments, astrocytes showed resilience to extended periods of OGD, which had little effect on Δψm during reperfusion, whereas GD caused a robust Δψm negativation. In case no Δψm negativation was observed after OGD, subsequent chemical oxygen deprivation (OD) induced by sodium azide caused depolarization, which, however, was significantly delayed as compared to normoxic group. When GD preceded OD for 12 h, Δψm hyperpolarization was induced by both GD and subsequent OD, but significant interaction between these conditions was not detected. However, when GD was extended to 48 h preceding OGD, hyperpolarization enhanced during reperfusion. This implicates synergistic effects of both conditions in that sequence. These findings provide novel information regarding the role of the two main substrates of electron transport chain (glucose and oxygen) and their hyperpolarizing effect on Δψm during substrate deprivation, thus shedding new light on mechanisms of astrocyte resilience to prolonged ischemic injury.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title: PLoS One
Publisher: Public Library of Science
ISSN: 1932-6203
Official Date: 2014
Dates:
DateEvent
2014Published
Volume: 9
Number: 2
Article Number: e90697
DOI: 10.1371/journal.pone.0090697
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)

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