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http://hdl.handle.net/11375/25920
Title: | Astrocytic Deficits in Maintaining Oxidative Homeostasis in the Fragile X Syndrome Cortex |
Authors: | Vandenberg, Gregory |
Advisor: | Scott, Angela |
Department: | Biology |
Keywords: | Fragile X Syndrome;Astrocyte;Mouse model;Oxidative stress;Mitochondrial respiration;Reactive species;Antioxidants;Physiological hypoxia |
Publication Date: | 2020 |
Abstract: | Fragile X Syndrome (FXS) is caused by the instability of a CGG-repeated tract at the 5’ end of the Fmr1 transcript. This instability causes silencing of the gene coding for FMRP. Higher levels of reactive oxygen species, lipid peroxidation, and protein oxidation within brain tissue have been found to be associated with the disease. These imbalances, along with altered levels of components of the glutathione system, provide evidence for increased oxidative stress. Astrocytes, glial cells within the brain, have many functions within neurodevelopment. Specifically, they regulate growth and synaptic contacts of neurons, regulate the level of excitability of synapses, and protect neurons at high levels of activity. To protect neurons from oxidative stress, astrocytes maintain oxidative homeostasis through their mitochondrial electron transport and antioxidant systems. This study examines the relationship between oxidative stress and FXS by assessing mitochondrial function and the antioxidant system of astrocytes. Using the Fmr1 knockout (KO) mouse model, mitochondrial respiration, and reactive oxygen species (ROS) production was analyzed in cultured cortical astrocytes. Astrocytes collected from male and female mice were analyzed under both normoxic and hypoxic conditions. In addition, western blots were conducted on both cortical tissue and cultured cortical astrocytes to determine potential differences in enzyme expression. Results indicate elevations of leak state respiration and ROS production in Fmr1 KO cultured cortical astrocytes alongside alterations in antioxidant and NADPH-oxidase expression. Characterization of mitochondrial function and the antioxidant system of astrocytes will be highly valuable to the understanding of glial roles during brain development and could provide future insight to direct clinically relevant studies of FXS and other neurodevelopment disorders. |
URI: | http://hdl.handle.net/11375/25920 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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vandenberg_gregory_g_2020Sept_MSc.pdf | Gregory Vandenberg's Masters Thesis | 1.62 MB | Adobe PDF | View/Open |
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