کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3070590 1580737 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Manganese superoxide dismutase protects mouse cortical neurons from chronic intermittent hypoxia-mediated oxidative damage
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Manganese superoxide dismutase protects mouse cortical neurons from chronic intermittent hypoxia-mediated oxidative damage
چکیده انگلیسی

Obstructive sleep apnea (OSA) syndrome has been recognized as a highly prevalent public health problem and is associated with major neurobehavioral morbidity. Chronic intermittent hypoxia (CIH), a major pathological component of OSA, increases oxidative damage to the brain cortex and decreases neurocognitive function in rodent models resembling human OSA. We employed in vitro and in vivo approaches to identify the specific phases and subcellular compartments in which enhanced reactive oxygen species (ROS) are generated during CIH. In addition, we utilized the cell culture and animal models to analyze the consequences of enhanced production of ROS on cortical neuronal cell damage and neurocognitive dysfunction. In a primary cortical neuron culture system, we demonstrated that the transition phase from hypoxia to normoxia (NOX) during CIH generates more ROS than the transition phase from NOX to hypoxia or hypoxia alone, all of which generate more ROS than NOX. Using selective inhibitors of the major pathways underlying ROS generation in the cell membrane, cytosol, and mitochondria, we showed that the mitochondria are the predominant source of enhanced ROS generation during CIH in mouse cortical neuronal cells. Furthermore, in both cell culture and transgenic mice, we demonstrated that overexpression of MnSOD-decreased CIH-mediated cortical neuronal apoptosis, and reduced spatial learning deficits measured with the Morris water maze assay. Together, the data from the in vitro and in vivo experiments indicate that CIH-mediated mitochondrial oxidative stress may play a major role in the neuronal cell loss and neurocognitive dysfunction in OSA. Thus, therapeutic strategies aiming at reducing ROS generation from mitochondria may improve the neurobehavioral morbidity in OSA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 28, Issue 2, November 2007, Pages 206–215
نویسندگان
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