Buried Alive! Arrested Development and Hypoxia Tolerance in the Naked Mole-Rat

Abstract

Event Abstract Back to Event Buried Alive! Arrested Development and Hypoxia Tolerance in the Naked Mole-Rat John Larson1*, Bethany L. Peterson2, Madeline Romano1 and Thomas J. Park2 1 University of Illinois at Chicago, Psychiatry, United States 2 University of Illinois at Chicago, Biological Sciences, United States Naked mole-rats are highly social subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. In addition to systemic factors such as reduced metabolic rate, hypothermia, and high-affinity hemoglobin, we found that brain slices from adult naked mole-rats are also remarkably resistant to hypoxia. We hypothesized that extreme brain resistance to hypoxia may reflect an arrested state of brain development in which the well-known tolerance of neonatal brain tissue to hypoxia is retained into the adult state. Hippocampal slices from adult naked mole-rats manifest extreme tolerance to hypoxia in at least three ways, compared to other mammal species: synaptic transmission is maintained under more hypoxic conditions; anoxic depolarization time is delayed three times longer after total oxygen deprivation, and slices recover electrophysiological responsiveness after much longer period of anoxia. Since hypoxia tolerance is a characteristic of neonatal brains generally, we examined naked mole-rat brains for other neonatal characteristics potentially related to hypoxia tolerance. NMDA receptors in many brain areas show developmental changes in which GluN2B and GluN2D subunits decrease with maturation while GluN2A and GluN2C increase in abundance. We found that adult naked mole-rat brain retains more GluN2D into adulthood than do mice. GluN2D has also been linked to hypoxia tolerance in neonatal mice and rats, since channels containing this subunit exhibit decreased openings under low-oxygen conditions. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death is the elevation of intracellular calcium concentration. Using calcium imaging methods, we found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. Both species demonstrated more calcium accumulation at older ages; however, the older naked mole-rats showed a smaller calcium response than even the neonatal mice. Finally, we measured the ATP content of hippocampal slices from adult mice and naked mole-rats before and during an episode of anoxia. Naked mole-rat slices had considerably higher resting levels of ATP than did mouse slices. These results are also consistent with the arrested development hypothesis since ATP levels in mouse are higher in the early postnatal period than in adulthood. During anoxia, ATP levels declined similarly in slices from mice and naked mole-rats. In summary, adult naked mole-rat brain exhibits a remarkable tolerance to hypoxia. Considering that brain is an important consumer of oxygen, we suggest that evolution in a chronically hypoxic environment may have resulted in an adaptation involving arrested brain development such that adult naked mole-rat brain maintains neonatal hypoxia tolerance into adulthood. Keywords: Anoxia, ATP, Calcium, fossorial, Hippocampus, NMDA Conference: Tenth International Congress of Neuroethology, College Park. Maryland USA, United States, 5 Aug - 10 Aug, 2012. Presentation Type: Invited Symposium (only for people who have been invited to a particular symposium) Topic: Cellular Properties Citation: Larson J, Peterson BL, Romano M and Park TJ (2012). Buried Alive! Arrested Development and Hypoxia Tolerance in the Naked Mole-Rat. Conference Abstract: Tenth International Congress of Neuroethology. doi: 10.3389/conf.fnbeh.2012.27.00047 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Apr 2012; Published Online: 07 Jul 2012. * Correspondence: Prof. John Larson, University of Illinois at Chicago, Psychiatry, Chicago, IL, 60612, United States, jrlarson@uic.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers John Larson Bethany L Peterson Madeline Romano Thomas J Park Google John Larson Bethany L Peterson Madeline Romano Thomas J Park Google Scholar John Larson Bethany L Peterson Madeline Romano Thomas J Park PubMed John Larson Bethany L Peterson Madeline Romano Thomas J Park Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.