Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-09-19 | GSE98746 | GEO
Project description:RNA-seq of breeding and non-breeding naked mole-rats and guinea pigs
| PRJNA386015 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-15 | GSE185724 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-04-20 | GSE148969 | GEO
Project description:Osteoarthritis (OA) is the most prevalent disabling disease, affecting quality of life and contributing to morbidity, particularly during aging. Current treatments for OA are limited to palliation: pain management and surgery for end-stage disease. Innovative approaches and animal models are needed to develop curative treatments for OA. Here, we investigated the naked mole-rat (NMR) as a potential model of OA resistance. NMR is a small rodent with the maximum lifespan of over 30 years, resistant to a wide range of age-related diseases. NMR tissues accumulate large quantities of unique, very high molecular weight, hyaluronan (HA). HA is a major component of cartilage and synovial fluid. Importantly, both HA molecular weight and cartilage stiffness decline with age and progression of OA. As increased polymer length is known to result in stiffer material, we hypothesized that NMR high molecular weight HA contributes to stiffer cartilage. Our analysis of biomechanical properties of NMR cartilage revealed that it is significantly stiffer than mouse cartilage. Furthermore, NMR chondrocytes were highly resistant to traumatic damage. In vivo experiments using an injury-induced model of OA revealed that NMRs were highly resistant to OA. While similarly treated mice developed severe cartilage degeneration, NMRs did not show any signs of OA. Our study shows that NMRs are remarkably resistant to OA, and this resistance is likely conferred by high molecular weight HA. This work suggests that NMR is a useful model to study OA resistance and NMR high molecular weight HA may hold therapeutic potential for OA treatment.
| S-EPMC7681040 | biostudies-literature
Project description:Elevated prolactin (PRL) has been associated with the expression of social and cooperative behaviours in a number of vertebrate species, as well as suppression of reproduction. As social mole-rats exhibit both of these traits, PRL is a prime candidate in mediating their social phenotype. While naked and Damaraland mole-rats (NMRs and DMRs) have evolved eusociality independently within their family, both species exhibit an extreme skew in lifetime reproductive success, with breeding restricted to a single female and one or two males. Non-breeding NMRs of both sexes are physiologically inhibited from reproducing, while in DMRs only the non-breeding females are physiologically suppressed. Newly emerging work has implicated the dopamine system and PRL as a component in socially induced reproductive suppression and eusociality in NMR, but the DMR remains unstudied in this context. To investigate evolutionary convergence in the role of PRL in shaping African mole-rat eusociality, we determined plasma PRL concentrations in breeders and non-breeders of both sexes, comparing DMRs with NMRs. Among samples from non-breeding NMRs 80% had detectable plasma PRL concentrations. As a benchmark, these often (37%) exceeding those considered clinically hyperprolactinaemic (25 ng ml-1) in humans: mean ± s.e.m.: 34.81 ± 5.87 ngml-1; range 0.00-330.30 ng ml-1 Conversely, 85% of non-breeding DMR samples had undetectable values and none had concentrations above 25 ng ml-1: 0.71 ± 0.38 ng ml-1; 0.00-23.87 ngml-1 Breeders in both species had the expected variance in plasma PRL concentrations as part of normal reproductive function, with lactating queens having significantly higher values. These results suggest that while elevated PRL in non-breeders is implicated in NMR eusociality, this may not be the case in DMRs, and suggests a lack of evolutionary convergence in the proximate control of the social phenotype in these mole-rats.
| S-EPMC6012705 | biostudies-literature
Project description:Naked mole rats (NMRs) are among the most hypoxia-tolerant mammals. Other species respond to hypoxia by either escaping the hypoxic environment or drastically decreasing behavioural activity and body temperature (Tb) to conserve energy. However, NMRs rarely leave their underground burrows, which are putatively hypoxic and thermally stable near the NMRs' preferred Tb Therefore, we asked whether NMRs are able to employ behavioural and thermoregulatory strategies in response to hypoxia despite their need to remain active and the minimal thermal scope in their burrows. We exposed NMRs to progressively deeper levels of hypoxia (from 21 to 0% O2) while measuring their behaviour and Tb Behavioural activity decreased 40-60% in hypoxia and Tb decreased slightly in moderate hypoxia (5-9%) and then further with deeper hypoxia (3% O2). However, even at 3% O2 NMRs remained somewhat active and warm, and continued to explore their environment. Remarkably, NMRs were active for greater than 90 s in acute anoxia and Tb and metabolic rate decreased rapidly. We conclude that NMRs are adapted to remain awake and functional even at the extremes of their hypoxia-tolerance. This adaptation likely reflects variable and challenging levels of environmental hypoxia in the natural habitat of this species.
| S-EPMC5746535 | biostudies-literature
Project description:The long-living naked mole-rat (NMR) shows negligible senescence and resistance to age-associated diseases. Recent evidence, based on protein-level assays, suggests that enhanced protein homeostasis machinery contributes to NMR stress-resistance and longevity. Here, we develop NMR-specific, transcriptional assays for measuring the unfolded protein response (UPR), a component of ER proteostasis. By varying doses and response times of pharmacological ER stressors applied to NMR kidney fibroblasts, we probe the NMR UPR in detail, demonstrating that NMR fibroblasts have a higher UPR activation threshold compared to mouse fibroblasts under mild ER-stress induction; whereas temporal analysis reveals that severe ER-stress induction results in no comparative differences. Probing NMR UPR activation with our robust assays may lead to insights into the proteostasis and ageing relationship.
| S-EPMC7453385 | biostudies-literature
Project description:Neuropathic pain is a chronic disease state resulting from injury to the nervous system. This type of pain often responds poorly to standard treatments and occasionally may get worse instead of better over time. Patients who experience neuropathic pain report sensitivity to cold and mechanical stimuli. Since the nociceptive system of African naked mole-rats contains unique adaptations that result in insensitivity to some pain types, we investigated whether naked mole-rats may be resilient to sensitivity following nerve injury. Using the spared nerve injury model of neuropathic pain, we showed that sensitivity to mechanical stimuli developed similarly in mice and naked mole-rats. However, naked mole-rats lacked sensitivity to mild cold stimulation after nerve injury, while mice developed robust cold sensitivity. We pursued this response deficit by testing behavior to activators of transient receptor potential (TRP) receptors involved in detecting cold in naïve animals. Following mustard oil, a TRPA1 activator, naked mole-rats responded similarly to mice. Conversely, icilin, a TRPM8 agonist, did not evoke pain behavior in naked mole-rats when compared with mice. Finally, we used RNAscope to probe for TRPA1 and TRPM8 messenger RNA expression in dorsal root ganglia of both species. We found increased TRPA1 messenger RNA, but decreased TRPM8 punctae in naked mole-rats when compared with mice. Our findings likely reflect species differences due to evolutionary environmental responses that are not easily explained by differences in receptor expression between the species.
| S-EPMC7475789 | biostudies-literature
Project description:The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype-ARF suppression-induced senescence (ASIS)-that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR.
| S-EPMC4866046 | biostudies-literature