Eaton, Liam2026-03-042026-03-042026-03-04http://hdl.handle.net/10393/51429https://doi.org/10.20381/ruor-31786Oxygen is essential for aerobic metabolism and for the concomitant generation of reactive oxygen species (ROS) as a by-product. ROS are important cellular signaling molecules, but sudden changes in oxygen availability may disrupt ROS homeostasis, which can subsequently induce oxidative damage and promote cellular dysfunction and death. Despite this, many animals have adapted to life in hypoxic conditions, in part by developing strategies to maintain ROS homeostasis and avoid accumulation of oxidative damage. Of particular interest are hypoxia-tolerant naked mole-rats (Heterocephalus glaber), which are thought to putatively experience recurrent hypoxia/reoxygenation cycles in their burrows. This thesis investigates mechanisms that contribute to ROS balance in naked mole-rat brain cells, and elucidates novel and beneficial adaptations for life in intermittent hypoxia. In chapter 2, I used fluorescent microscopy to determine that, unlike in mice, ROS homeostasis is maintained in naked mole-rat cortical cells exposed to hypoxia (~1% O₂, ~7.4 mm Hg), oxygen glucose deprivation, exogenous ROS application, and respective reperfusions. Then, in chapter 3, I used pharmacological tools to inhibit known sources of endogenous ROS generation. Unfortunately, relative contributions of key ROS generators remain inconclusive, but I found evidence which suggests that XOR may play a major role in ROS scavenging. Finally, I used a high-throughput plate assay to compare ROS scavenging and found that naked mole-rat permeabilized forebrain homogenates have an enhanced ROS scavenging capacity relative to mice, largely due to improved glutathione-dependent scavenging (Chapter 4). Taken together, these findings provide support for my hypothesis that naked mole-rat brain is better adapted for life in intermittent hypoxic conditions, such that naked mole-rat brain cells are better able to prevent oxidative damage during hypoxia and reoxygenation compared to similar cells in hypoxia-intolerant mice.enHypoxiaNaked mole-ratReactive oxygen speciesBrainThesis