Biology subjects

Bennett, N. C.

Publications and source records attributed to Bennett, N. C..

12 recordsLinked to original sources

bioRxiv2026

Sociality, diurnal temperature range and isothermality: Significant determinants of mass-independent resting metabolic rate in subterranean African mole-rats (Superfamily Bathyergidae)

Animals exhibit a diverse range of sociality from the strictly solitary to the highly social. Different forms of sociality have evolved in response to ecological constraints and selective habitat pressures, which are governed by the energetic and fitness costs to an individual. Uniquely among mammals, the clade of African mole-rats (Bathyergidae and Heterocephalidae) covers three distinct life-history forms of sociality: solitary, social and eusocial species. This variety in social structure makes them a model clade to study how metabolic traits vary between different forms of sociality. Resting metabolic rates (RMR) of seven African mole-rat species, ranging from solitary to eusocial, were measured using open-flow respirometry. Results were combined with published data, enabling the inclusion and statistical analysis of 16 species in total. We identified distinct allometric scaling of RMR, with eusocial species exhibiting a considerably greater rise in RMR with increases in body mass. This is likely attributable to reproductive and behavioural divisions of labour, and mass-dependent colony roles in eusocial species. Phylogenetically-informed analyses further identified that sociality, in addition to select bioclimatic traits - diurnal temperature range ({degrees}C) and isothermality (%) - significantly explain variation in the mass-independent RMR of African mole-rats. These findings elucidate, for the first time, that sociality can be a determinant of RMR, and calls for further study to identify the wider significance of sociality on mammalian metabolism, as well as exploring the allometric scaling of metabolic rate with respect to mammalian sociality.

physiology↗

bioRxiv2025

Bacteria-induced colitis in naked mole rats is alleviated by probiotic treatment: a new mammalian model for acute inflammatory disease

Enteropathogenic bacteria are a major cause of morbidity and mortality globally. Mouse models have been indispensable in advancing our understanding of infectious diseases caused by intestinal pathogens and in identifying physical, chemical and immunological barriers that limit these infections. However, there are significant differences between laboratory mice and human intestinal microbiota and immunobiology that underscore the need to develop other models that recapitulate the disease pathology and mucosal immune responses of human enteric diseases. Here we report how the pathogenic expansion of Citrobacter braakii in naked mole rats (NMRs) leads to colonic inflammation and epithelial injury that mimics pathological features of human hemorrhagic colitis. We observe mucosal erosions, ulcerations, depletion of goblet cells, extension of proliferative compartments to the surface of the glands, and active inflammation in the colonic lamina propria of infected NMRs. Without intervention, systemic inflammation associated with sepsis ensues in infected NMRs and results in high mortality. Interestingly, we demonstrate a strong therapeutic effect of probiotics comprising Lactobacillus, Bifidobacterium, Streptococcus salvarius subsp. thermophilus and Enterococcus faecium strains. Treatment with probiotics induces mucosal healing and restores intestinal homeostasis, including suppression of excessive proliferation of epithelial cells, replenishment of goblet cells and also has an anti-inflammatory effect. Taken together, we demonstrate that NMRs, beyond their use as an anti-ageing and disease-resistance model, can also be used to address disease mechanisms underlying infectious colitis, including disruptions in the mucosal barrier permeability, gut microbial ecology and in local and systemic immune regulation; and in testing functional probiotics strains as potential therapeutics.

pathology↗

bioRxiv2024

Sociality shapes mitochondrial adaptations supporting hypoxia tolerance

Oxygen deprivation or hypoxia is poorly dealt with by most terrestrial species and often leads to permanent tissue damage and death. One prominent exception is the naked mole-rat (Heterocephalus glaber) which is remarkably adapted to withstand prolonged periods ([~]18 mins) of severe hypoxia, a trait likely driven by its crowded underground lifestyle. Other African mole-rat species are less social or entirely solitary like the Cape mole-rat (Georychus capensis). Here, we asked whether cellular and molecular adaptations to hypoxia map to social traits. We discovered that at the cellular level naked mole-rat fibroblasts survive >30 hours in 1% oxygen, while fibroblasts from terrestrial or non-social mole-rat species (human, mouse and Cape mole-rat) die rapidly under hypoxic conditions. We further show that naked mole-rat mitochondria have evolved morphological, functional and proteomic adaptations crucial for hypoxia resistance, remaining unaffected after long periods of severe hypoxia. We identify the mitochondrial protein Optic Atrophy 1 (OPA1) as a key player in naked mole-rat hypoxia resilience. Naked mole-rat mitochondria not only express more protective forms of OPA1, but also harbor a structurally unique isoform that likely protects cells from hypoxic damage. We show that evolutionary changes including the functionalization of a unique Opa1 exon support mitochondrial mediated cellular protection. Indeed, knockdown of OPA1 in naked mole-rat cells is sufficient to render them equally susceptible to hypoxia as human cells or cells from non-social African species. Our study demonstrates how molecular evolution drives unique adaptations that enable cells to achieve unprecedented resistance to hypoxic damage. We also show that molecular changes at the level of mitochondria are crucial in conferring hypoxia resistance. Our results thus chart a novel molecular path to understand how robust cellular hypoxia resistance can be achieved. Such knowledge may eventually inspire novel strategies to circumvent the consequences of hypoxic-damage in humans.

physiology↗

bioRxiv2023

Naked mole rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles

The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, RNAseq and metabolomics of cardiac tissue from naked mole-rats was compared to other African mole-rat genera. We identified metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1 was observed while downstream hypoxia responsive-genes were down regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts showed reduced succinate build-up during ischemia and negligible tissue damage following ischemia-reperfusion injury. These adaptive evolutionary traits reflect a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span. One Sentence SummaryNaked mole-rats have metabolic adaptations distinct from other subterranean genera rendering them resistant to cardiovascular pathology.

physiology↗

bioRxiv2021

Immune competence and spleen size scale with colony status in the naked mole-rat

Naked mole-rats (NM-R; Heterocephalus glaber) live in multi-generational colonies with a social hierarchy, show low cancer incidence and long life-spans. Here we asked if such extreme physiology might have an immune component. The spleen is the largest lymphoid organ and plays an essential role in response to immunological insults and may participate in combating cancer and slowing ageing. We investigated the anatomy, molecular composition and function of the NM-R spleen using RNA-sequencing and histological analysis in healthy animals. We found that spleen size in healthy NM-Rs varies considerably. We therefore classified NM-Rs according to spleen size as NM-Rs with small spleens or enlarged spleens. Animals with enlarged spleens showed potentially better anti-microbial profiles and were much more likely to have a high rank within the colony. Splenomegaly was associated with infection in sick NM-Rs, but not in NM-Rs with enlarged spleens. In all healthy NM-Rs splenic erythropoiesis, megakaryopoiesis and myelopoiesis were increased, but B lymphopoiesis was reduced and splenic marginal zone showed markedly altered morphology when compared to other rodents. However, in NM-Rs lymphocytes were found in secondary sites such as lymph nodes, gut lymphoid nodules and thymus. Thus, the NM-R spleen is a major site of adult hematopoiesis under normal physiological conditions. Overall, the NM-R immune system seems to rely mainly on innate immune responses with a more restricted adaptive immune response. We propose that the anatomical plasticity of the spleen might be regulated by social interaction and gives immunological advantage to increase the life-span of higher ranked animals.

immunology↗

bioRxiv2021

Zika virus infection of pregnant Ifnar1-/- mice triggers strain-specific differences in fetal outcomes

Zika virus (ZIKV) is a flavivirus that causes a constellation of adverse fetal outcomes collectively termed Congenital Zika Syndrome (CZS). However, not all pregnancies exposed to ZIKV result in an infant with apparent defects. During the 2015-2016 American outbreak of ZIKV, CZS rates varied by geographic location. The underlying mechanisms responsible for this heterogeneity in outcomes have not been well defined. Therefore, we sought to characterize and compare the pathogenic potential of multiple Asian/American-lineage ZIKV strains in an established Ifnar1-/- pregnant mouse model. Here, we show significant differences in the rate of fetal demise following maternal inoculation with ZIKV strains from Puerto Rico, Panama, Mexico, Brazil, and Cambodia. Rates of fetal demise broadly correlated with maternal viremia but were independent of fetus and placenta virus titer, indicating that additional underlying factors contribute to fetus outcome. Our results, in concert with those from other studies, suggest that subtle differences in ZIKV strains may have important phenotypic impacts. With ZIKV now endemic in the Americas, greater emphasis needs to be placed on elucidating and understanding the underlying mechanisms that contribute to fetal outcome. IMPORTANCEZika virus (ZIKV) actively circulates in 89 countries and territories around the globe. ZIKV infection during pregnancy is associated with adverse fetal outcomes including birth defects, microcephaly, neurological complications, and even spontaneous abortion. Rates of adverse fetal outcomes vary between regions, and not every pregnancy exposed to ZIKV results in birth defects. Not much is known about how or if the infecting ZIKV strain is linked to fetal outcomes. Our research provides evidence of phenotypic heterogeneity between Asian/American-lineage ZIKV strains and provides insight into the underlying causes of adverse fetal outcomes. Understanding ZIKV strain-dependent pathogenic potential during pregnancy and elucidating underlying causes of diverse clinical sequelae observed during human infections is critical to understanding ZIKV on a global scale.

microbiology↗

bioRxiv2021

Naked mole-rats (Heterocephalus glaber) do not specialise on cooperative tasks

It has been proposed that naked mole-rat (Heterocephalus glaber) societies resemble those of eusocial insects by showing a division of labour among non-breeding individuals. Earlier studies suggested that non-breeders belong to distinct castes that specialise permanently or temporarily on specific cooperative tasks. In contrast, recent research on naked mole-rats has shown that behavioural phenotypes are continuously distributed across non-breeders and that mole-rats exhibit considerable behavioural plasticity suggesting that individuals may not specialise permanently on work tasks. However, it is currently unclear whether individuals specialise temporarily and whether there is a sex bias in cooperative behaviour among non-breeders. Here we show that non-breeding individuals vary in overall cooperative investment, but do not specialise on specific work tasks. Within individuals, investment into specific cooperative tasks such as nest building, food carrying and burrowing are positively correlated, and there is no evidence that individuals show trade-offs between these cooperative behaviours. Non-breeding males and females do not differ in their investment in cooperative behaviours and show broadly similar age and body mass related differences in cooperative behaviours. Our results suggest that non-breeding naked mole-rats vary in their overall contribution to cooperative behaviours and that some of this variation may be explained by differences in age and body mass. Our data provide no evidence for temporary specialisation, as found among some eusocial insects, and suggests that the behavioural organisation of naked mole-rats resembles that of other cooperatively breeding vertebrates more than that of eusocial insect species.

animal behavior and cognition↗

bioRxiv2020

Forces experienced by instrumented animals depend on lifestyle

Animal-attached devices have transformed our understanding of vertebrate ecology. However, to be acceptable, researchers must minimize tag-related harm. The long-standing recommendation that tag masses should not exceed 3% of the animals body mass ignores tag forces generated by movement. We used collar-attached accelerometers on four free-ranging carnivores, spanning two orders of magnitude in mass, to reveal that during movement, forces exerted by 3% tags were generally equivalent to 4-19% of the animals masses, with a record of 54% in a hunting cheetah. Controlled studies on domestic dogs revealed how the tag forces are dictated by animal gait and speed but appear largely invariant of body mass. This fundamentally changes how acceptable tag mass limits should be determined, requiring cognizance of animal athleticism. One Sentence SummaryThere can be no universal rule for collar-tag masses as a percentage of carrier mass since tag forces depend on lifestyle.

ecology↗

bioRxiv2020

Path tortuosity changes the transport cost paradigm in terrestrial animals

Animal movement paths are variously tortuous, with high turn rates predicted to be energetically costly, especially at high speeds. Animals travel most efficiently at the speed that gives the lowest cost of transport (COT), a well-defined point for movement in fluid media. However, theoretically, land animals should travel at their maximum speed to minimize COT, which they do not, instead travelling at walking pace. We measured oxygen consumption in humans to demonstrate that the energetic costs of turning increase disproportionately with both speed and angular velocity. This resulted in the minimum COT speed occurring at very low speeds, which reduced with increased path tortuosity. Data on turn rates from six free-ranging terrestrial species underpinned this because all individuals turned faster at the slowest speeds across the full speed range. The optimum movement speed for minimum COT in land animals thus depends on the environment and behavior since both affect track tortuosity.

ecology↗

bioRxiv2018

Specialized mechanoreceptor systems in rodent glabrous skin

Rodents use their forepaws to actively interact with their tactile environment. Studies on the physiology and anatomy of glabrous skin that makes up the majority of the forepaw are almost non-existent in the mouse. Here we developed a preparation to record from single sensory fibers of the forepaw and compared anatomical and physiological receptor properties to those of the hind paw glabrous and hairy skin. We found that the mouse forepaw skin is equipped with a very high density of mechanoreceptors; >3 fold more than hind paw glabrous skin. In addition, rapidly adapting mechanoreceptors that innervate Meissners corpuscles of the forepaw were several-fold more sensitive to slowly moving mechanical stimuli compared to their counterparts in the hind paw glabrous skin. All other mechanoreceptors types as well as myelinated nociceptors had physiological properties that were invariant regardless of which skin area they occupied. We discovered a novel D-hair receptor innervating a small group of hairs in the middle of the hind paw glabrous skin in mice. Glabrous D-hair receptors were direction sensitive albeit with an orientation sensitivity opposite to that described for hairy skin D-hair receptors. Glabrous D-hair receptors do not occur in all rodents, but are present in North American and African rodent species that diverged more than 65 million years ago. The function of these specialized hairs is unknown, but they are nevertheless evolutionarily very ancient. Our study reveals novel physiological specializations of mechanoreceptors in the glabrous skin that likely evolved to facilitate tactile exploration.

neuroscience↗

bioRxiv2018

Maternal stress increases cooperative behaviour of offspring in wild meerkats

The phenotype of parents can have long-lasting effects on the development of offspring as well as on their behaviour, physiology, and morphology as adults. In some cases, these changes may increase offspring fitness but, in others, they can elevate parental fitness at a cost to the fitness of their offspring. We show that in Kalahari meerkats (Suricata suricatta), the circulating glucocorticoid (GC) hormones of pregnant females affect the growth and cooperative behaviour of their offspring. We performed a 3-year experiment in wild meerkats to test the hypothesis that GC-mediated maternal effects reduce the potential for offspring to reproduce directly and therefore cause them to exhibit more cooperative behaviour. Daughters (but not sons) born to mothers treated with cortisol during pregnancy grew more slowly early in life and exhibited significantly more of two types of cooperative behaviour (pup rearing and feeding) once they were adults compared to offspring from control mothers. They also had lower measures of GCs as they aged, which could explain the observed increases in cooperative behaviour. Because early life growth is a crucial determinant of fitness in female meerkats, our results indicate that GC-mediated maternal effects may reduce the fitness of offspring, but may elevate parental fitness as a consequence of increasing the cooperative behaviour of their daughters.

animal behavior and cognition↗

bioRxiv2017

Molecular insights into the pathways underlying naked mole-rat eusociality

BackgroundEusociality is the highest level of social organization and naked mole-rats (NMR)s are amongst the few mammals showing this unique social behavior; nevertheless, little is known about the molecular mechanisms underlying the eusociality of NMRs.\n\nResultsGene expression profiling of NMR brain and gonads (ovary and testis), from animals belonging to different reproductive castes, revealed robust gene expression differences between reproductive and non-reproductive members of NMR colonies. In the brain, dopaminergic pathways appear to be potential players in NMR eusocial behaviour. Breeding animals (queens and breeding males) showed increased expression of genes involved in dopamine metabolism. Using immunohistochemistry, we notably found these differences to be in dopaminergic hypothalamic areas, which provide inhibitory control over the secretion of prolactin, amongst other regions. Furthermore, plasma prolactin concentrations were elevated in many non-breeders (of both sexes), often reaching levels exceeding that of pregnant or lactating queens, suggesting a role for hyperprolactinaemia in socially-induced reproductive suppression. We also found that the ovaries of non-breeding females are arrested at pre-pubertal stage. They contained fewer supporting stromal cells compared to queens, and had very low expression of the aromatase gene Cyp19A1 (a key enzyme in estrogen synthesis) compared to non-breeding females. In the testes, genes involved in post meiosis spermatogenesis and sperm maturation (Prm1, Prm2, Odf3 and Akap4) were highly expressed in breeding males compared to non-breeders, explaining the low sperm number and impaired sperm motility characteristic of non-breeding males.\n\nConclusionsOur study suggests that extreme reproductive skew, one of the defining features of eusociality, is associated with changes in expression of key components of dopamine pathways, which could lead to hypogonadism and a lifetime of socially-induced sterility for most NMRs.

neuroscience↗