Nest Carbon Dioxide Masks GABA-Dependent Seizure Susceptibility in the Naked Mole-Rat

African naked mole-rats were likely the first mammals to evolve eusociality, and thus required adaptations to conserve energy and tolerate the low oxygen (O-2) and high carbon dioxide (CO2) of a densely populated fossorial nest. As hypercapnia is known to suppress neuronal activity, we studied whether naked mole-rats might demonstrate energy savings in GABAergic inhibition. Using whole-colony behavioral monitoring of captive naked mole-rats, we found a durable nest, characterized by high CO2 levels, where all colony members spent the majority of their time. Analysis of the naked mole-rat genome revealed, uniquely among mammals, a histidine point variation in the neuronal potassium-chloride cotransporter 2 (KCC2). A histidine missense substitution mutation at this locus in the human ortholog of KCC2, found previously in patients with febrile seizures and epilepsy, has been demonstrated to diminish neuronal Cl- extrusion capacity, and thus impairs GABAergic inhibition. Seizures were observed, without pharmacological intervention, in adult naked mole-rats exposed to a simulated hyperthermic surface environment, causing systemic hypocapnic alkalosis. Consistent with the diminished function of KCC2, adult naked mole-rats demonstrate a reduced efficacy of inhibition that manifests as triggering of seizures at room temperature by the GABA(A) receptor (GABA(A)R) positive allosteric modulator diazepam. These seizures are blocked in the presence of nest-like levels of CO2 and likely to be mediated through GABA(A)R activity, based on in vitro recordings. Thus, altered GABAergic inhibition adds to a growing list of adaptations in the naked mole-rat and provides a plausible proximate mechanism for nesting behavior, where a return to the colony nest restores GABA-mediated inhibition.Peer reviewe

Recommendations of Common Data Elements to Advance the Science of Selfâ Management of Chronic Conditions

PurposeCommon data elements (CDEs) are increasingly being used by researchers to promote data sharing across studies. The purposes of this article are to (a) describe the theoretical, conceptual, and definition issues in the development of a set of CDEs for research addressing selfâ management of chronic conditions; (b) propose an initial set of CDEs and their measures to advance the science of selfâ management; and (c) recommend implications for future research and dissemination.Design and MethodsBetween July 2014 and December 2015 the directors of the National Institute of Nursing Research (NINR)â funded P20 and P30 centers of excellence and NINR staff met in a series of telephone calls and a faceâ toâ face NINRâ sponsored meeting to select a set of recommended CDEs to be used in selfâ management research. A list of potential CDEs was developed from examination of common constructs in current selfâ management frameworks, as well as identification of variables frequently used in studies conducted in the centers of excellence.FindingsThe recommended CDEs include measures of three selfâ management processes: activation, selfâ regulation, and selfâ efficacy for managing chronic conditions, and one measure of a selfâ management outcome, global health.ConclusionsThe selfâ management of chronic conditions, which encompasses a considerable number of processes, behaviors, and outcomes across a broad range of chronic conditions, presents several challenges in the identification of a parsimonious set of CDEs. This initial list of recommended CDEs for use in selfâ management research is provisional in that it is expected that over time it will be refined. Comment and recommended revisions are sought from the research and practice communities.Clinical RelevanceThe use of CDEs can facilitate generalizability of research findings across diverse population and interventions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134268/1/jnu12233_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134268/2/jnu12233.pd