Intensified Mitochondrial Hydrogen Peroxide Release Occurs in all Brain Regions, Affects Male as Well as Female Rett Mice, and Constitutes a Life-Long Burden

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dc.contributor.authorAdebayo, Olusegun
dc.date.accessioned2022-05-04T13:56:24Z
dc.date.available2022-05-04T13:56:24Z
dc.date.issued2020-11-06
dc.description.abstractThe neurodevelopmental disorder Rett syndrome (RTT) affects mostly females. Upon an apparently normal initial development, cognitive impairment, irregular breathing, motor dysfunction, and epilepsy occur. The complex pathogenesis includes, among others, mitochondrial impairment, redox imbalance, and oxidative damage. As these arise already in neonatal Rett mice, they were proposed contributors of disease progression. Several mitochondrial studies in RTT used either full brains or selected brain regions only. Here, we mapped mitochondria-related ROS generation brain wide. Using sophisticated multi-sample spectrofluorimetry, H2O2 release by isolated mitochondria was quantified in a coupled reaction of Amplex UltraRed and horseradish peroxidase. All brain regions and the entire lifespan were characterized in male and female mice. In WT mice, mitochondrial H2O2 release was usually highest in cortex and lowest in hippocampus. Maximum rates occurred at postnatal day (PD) 10 and they slightly declined with further maturation. Already at PD 10, male and female Rett mice showed exaggerated mitochondrial H2O2 releases in first brain regions and persistent brain-wide increases from PD 50 on. Interestingly, female Rett mice were more intensely affected than male Rett mice, with their brainstem, midbrain and hippocampus being most severely struck. In conclusion, we used a reliable multi-sample cuvette-based assay on mitochondrial ROS release to perform brain-wide analyzes along the entire lifespan. Mitochondrial H2O2 release in Rett mice is intensified in all brain regions, affects hemizygous males and heterozygous females, and involves all maturational stages. Therefore, intensified mitochondrial H2O2 release seriously needs to be considered throughout RTT pathogenesis and may constitute a potential therapeutic target.en_US
dc.identifier.citation3en_US
dc.identifier.issnPMID: 33160914
dc.identifier.urihttp://dspace.run.edu.ng:8080/jspui/handle/123456789/2620
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofseries696;108666
dc.subjectDisease progressionen_US
dc.subjectMecp2en_US
dc.subjectOxidative stressen_US
dc.subjectPathogenic mechanismen_US
dc.subjectReactive oxygen speciesen_US
dc.subjectRedox signalingen_US
dc.titleIntensified Mitochondrial Hydrogen Peroxide Release Occurs in all Brain Regions, Affects Male as Well as Female Rett Mice, and Constitutes a Life-Long Burdenen_US
dc.typeArticleen_US
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