TY - JOUR TI - Neuronal adaptive responses to oxygen deprivation DO - https://doi.org/doi:10.7282/T3VT1QNQ PY - 2012 AB - Adaptability to changing environmental oxygen levels is important for the survival of aerobic organisms. Neurons in particular are vulnerable to oxygen deprivation (hypoxia), and hypoxia-induced degeneration is a hallmark of ischemic stroke, a leading cause of morbidity and disability. Ischemic stroke damages neurons through a combination of hypoxia-induced neuronal membrane depolarization, excess glutamate receptor activation, altered intracellular calcium homeostasis, and mitochondrial dysfunction. Neurons from different species or even from different brain regions of the same species have varying tolerances to oxygen deprivation, yet little is known about how neurons adapt to the stress of oxygen deprivation. Examining the causality of this differential resistance is particularly challenging in mammalian neurons given their inherent sensitivity to this stress. The soil nematode C. elegans serves as a hypoxia-adaptable model organism that can be used to examine how neurons handle oxygen deprivation. In the dissertation work presented here, I have employed C. elegans to study the hypoxic regulation of two key cell biological components important for the progression of hypoxia–induced neuronal death: glutamate receptors and mitochondria. In these studies, I report our identification of a novel variant of the hypoxia response pathway dedicated to the modulation of C. elegans glutamate receptor trafficking. In addition, I report that the dynamics of mitochondrial fission and fusion are altered in response to oxygen deprivation in C. elegans neurons. I also present data suggesting that the canonical hypoxia response pathway regulates this dynamic response. These alterations in glutamate receptor trafficking and mitochondrial dynamics are accompanied by behavioral changes and possibly promote survival in response to oxygen deprivation. My findings indicate that neurons protect themselves by executing a complex and multilayered homeostatic response to reduced oxygen availability that incorporates both transcriptional and posttranslational mechanisms. KW - Neuroscience KW - Neurons KW - Oxygen consumption (Physiology) LA - eng ER -