Naked mole-rats are unusual because they combine a subterranean lifestyle with living in large colonies. With many animals breathing the same stale air, oxygen supplies become low. Consistent with this, naked mole-rats are extremely tolerant to oxygen deprivation. Their brain is resistant to the effects of oxygen deprivation. The goal of the project is to identify the underlying physiological and genetic factors that give the naked mole-rat its tolerance. This will be important for understanding the diverse ways that animals can change to fit their environment. It will also be important for identifying new ways of surviving oxygen deprivation, which happens in the brain of a human who suffers a heart attack. Blood can no longer carry oxygen to the brain when the heart fails. The project also includes training graduate and undergraduate students to be scientists. Project staff will interact with the public at a free city zoo to inform people about the interesting biology of the naked mole-rat.
The problem to be studied is, how do naked mole-rats achieve extreme brain tolerance to oxygen deprivation? This will be studied using physiological, biochemical, and genetic techniques. Physiological approaches will include recording electroencephalograms (EEG) and quantifying metabolites related to anaerobic metabolism in animals exposed to hypoxia. The project will also use hippocampal brain slices to measure age-related changes in basic synaptic phenomena including long-term potentiation and long-term depression. Mass spectrometry will be used to determine the functionality (phosphorylation dynamics) of phosphorylation sites on hypoxia-induced programed cell death pathways. Finally, CRISPR/cas9 techniques will be used to produce both cell lines and mutant mice that carry naked mole-rat mutations in hypoxia-induced programed cell death pathways. The results are expected to reveal new ways of establishing brain protection from oxygen deprivation.
