Extreme Resistance to Oxygen Deprivation in Brain Tissue from the Naked Mole-Rat

The naked mole-rat lives in large colonies living completely underground, a very unique way of life. This leads to an environment where the air is low in oxygen and high in carbon dioxide. Adaptations in blood and metabolism have been previously reported in the naked mole-rat that help it survive these conditions. My study is aimed at specifically examining the tolerance to low oxygen (hypoxia) in the brain of this unusual species. My working hypothesis was that naked mole-rats retain neonatal protective characteristics against hypoxia into adulthood. First we exposed whole animals to no oxygen (anoxia) to see how long they survived. A group of naked mole-rats was exposed for around 6 minutes and still recovered once put back in room air. This is remarkable when compared to mice, which only survived around 45 seconds and did not recover. We then measured the levels of ATP in the brains of adult naked mole-rats compared to adult mice and neonatal mice. This is important because ATP is the energy of the brain and oxygen is needed for its synthesis. We found that ATP stores in adult naked mole-rat brain depleted slower than in adult mouse brain, however, it was not as slow as in neonatal mouse brain. Next, since many hypoxia-tolerant model systems are able to prevent an increase in internal calcium that leads to cell death during hypoxia, we wanted to establish if naked mole-rats could prevent this as well. We determined that in hippocampal brain slices from naked mole-rats the increase in internal calcium was significantly reduced compared to both neonatal and weanling mice. Lastly, we wanted to find out if the adult naked mole-rat brain retained more of the NMDA receptor subunit NR2D into adulthood compared to adult mouse brain. This subtype closes during hypoxia and is usually expressed more in neonatal mammals than in adults. We revealed that adult naked mole-rats do have a higher proportion of the NR2D subunit in adulthood compared to mice. These finding lead us to conclude that naked mole-rats are retaining neonatal protective characteristics against hypoxia.