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1.
PLoS One ; 17(9): e0273098, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36107951

RESUMO

Naked mole-rats are a long-lived rodent species (current lifespan >37 years) and an increasingly popular biomedical model. Naked mole-rats exhibit neuroplasticity across their long lifespan. Previous studies have begun to investigate their neurogenic patterns. Here, we test the hypothesis that neuronal maturation is extended in this long-lived rodent. We characterize cell proliferation and neuronal maturation in established rodent neurogenic regions over 12 months following seven days of consecutive BrdU injection. Given that naked mole-rats are eusocial (high reproductive skew where only a few socially-dominant individuals reproduce), we also looked at proliferation in brain regions relevant to the social-decision making network. Finally, we measured co-expression of EdU (newly-born cells), DCX (immature neuron marker), and NeuN (mature neuron marker) to assess the timeline of neuronal maturation in adult naked mole-rats. This work reaffirms the subventricular zone as the main source of adult cell proliferation and suggests conservation of the rostral migratory stream in this species. Our profiling of socially-relevant brain regions suggests that future work which manipulates environmental context can unveil how newly-born cells integrate into circuitry and facilitate adult neuroplasticity. We also find naked mole-rat neuronal maturation sits at the intersection of rodents and long-lived, non-rodent species: while neurons can mature by 3 weeks (rodent-like), most neurons mature at 5 months and hippocampal neurogenic levels are low (like long-lived species). These data establish a timeline for future investigations of longevity- and socially-related manipulations of naked mole-rat adult neurogenesis.


Assuntos
Ratos-Toupeira , Neurogênese , Animais , Bromodesoxiuridina , Longevidade/fisiologia , Ratos-Toupeira/fisiologia , Neurônios/fisiologia
2.
Int J Mol Sci ; 23(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36012332

RESUMO

The reason for the exceptional longevity of the naked mole rat (Heterocephalus glaber) remains a mystery to researchers. We assumed that evolutionarily, H. glaber acquired the ability to quickly stabilize the functioning of mitochondria and endoplasmic reticulum (ER) to adjust metabolism to external challenges. To test this, a comparison of the hepatic mitochondria and ER of H. glaber and C57BL/6 mice was done. Electron microscopy showed that 2-months-old mice have more developed rough ER (RER) than smooth ER (SER), occupying ~17 and 2.5% of the hepatocytic area correspondingly, and these values do not change with age. On the other hand, in 1-week-old H. glaber, RER occupies only 13% constantly decreasing with age, while SER occupies 35% in a 1-week-old animal, constantly rising with age. The different localization of mitochondria in H. glaber and mouse hepatocytes was confirmed by confocal and electron microscopy: while in H. glaber, mitochondria were mainly clustered around the nucleus and on the periphery of the cell, in mouse hepatocytes they were evenly distributed throughout the cell. We suggest that the noted structural and spatial features of ER and mitochondria in H. glaber reflect adaptive rearrangements aimed at greater tolerance of the cellular system to challenges, primarily hypoxia and endogenous and exogenous toxins. Different mechanisms of adaptive changes including an activated hepatic detoxification system as a hormetic response, are discussed considering the specific metabolic features of the naked mole rat.


Assuntos
Mitocôndrias , Ratos-Toupeira , Animais , Retículo Endoplasmático , Hepatócitos , Hipertrofia , Camundongos , Camundongos Endogâmicos C57BL
3.
Proc Biol Sci ; 289(1980): 20220878, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35946148

RESUMO

Life underground often leads to animals having specialized auditory systems to accommodate the constraints of acoustic transmission in tunnels. Despite living underground, naked mole-rats use a highly vocal communication system, implying that they rely on central auditory processing. However, little is known about these animals' central auditory system, and whether it follows a similar developmental time course as other rodents. Naked mole-rats show slowed development in the hippocampus suggesting they have altered brain development compared to other rodents. Here, we measured morphological characteristics and voltage-gated potassium channel Kv3.3 expression and protein levels at different key developmental time points (postnatal days 9, 14, 21 and adulthood) to determine whether the auditory brainstem (lateral superior olive and medial nucleus of the trapezoid body) develops similarly to two common auditory rodent model species: gerbils and mice. Additionally, we measured the hearing onset of naked mole-rats using auditory brainstem response recordings at the same developmental timepoints. In contrast with other work in naked mole-rats showing that they are highly divergent in many aspects of their physiology, we show that naked mole-rats have a similar hearing onset, between postnatal day (P) 9 and P14, to many other rodents. On the other hand, we show some developmental differences, such as a unique morphology and Kv3.3 protein levels in the brainstem.


Assuntos
Tronco Encefálico , Ratos-Toupeira , Animais , Percepção Auditiva/fisiologia , Tronco Encefálico/anatomia & histologia , Gerbillinae , Hipocampo , Camundongos , Ratos-Toupeira/fisiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-35907588

RESUMO

Naked mole-rats are among the few mammals with the ability to endure severe hypoxia. These unique rodents use metabolic rate depression along with various molecular mechanisms to successfully overcome the challenges of oxygen-limitation, which they experience in their underground borrows. While studies have reported that naked mole-rats exhibit inherently higher levels of oxidative damage across their lifespan as compared to mice, it has yet to be determined whether naked mole-rats are vulnerable to oxidative damage during periods of low oxygen exposure. To investigate this phenomenon, we examined cellular oxidative damage markers of macromolecules: DNA oxidation determined as 8-oxo-2'deoxyguanosine (8-OHdG8) levels, RNA oxidation as 8-hydroxyguanosine (8-OHG), protein carbonylation, and lipid peroxidation in normoxic (control), acute (4 h at 7% O2), and chronic (24 h at 7% O2) hypoxia-exposed naked mole-rats. Brain appears to be the most resilient to hypoxia-induced oxidative damage, with both brain and heart exhibiting enhanced antioxidant capacity during hypoxia. Levels of DNA and RNA oxidation were minimally changed in all tissues and no changes were observed in protein carbonylation. Most tissues experienced lipid peroxidation, with liver displaying a 9.6-fold increase during hypoxia. Concomitantly, levels of DNA damage repair proteins were dynamically regulated in a tissue-specific manner, with white adipose displaying a significant reduction during hypoxia. Our findings show that naked mole-rats largely avoid hypoxia-induced oxidative damage, possibly due to their high tolerance to redox stress, or to reduced oxidative requirements made possible during their hypometabolic response when oxygen supply is limited.


Assuntos
Ratos-Toupeira , Estresse Oxidativo , Animais , Hipóxia , Camundongos , Ratos-Toupeira/metabolismo , Estresse Oxidativo/fisiologia , Oxigênio/metabolismo , RNA/metabolismo
5.
EMBO J ; 41(15): e111759, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35781819

RESUMO

Analysis of functional deterioration of the blood system during ageing has been largely confined to the mouse and human system. In this issue, Emmrich et al (2022) report the first comprehensive characterisation of the haematopoietic system of the naked mole-rat (NMR), an exceptionally long-lived rodent, highlighting its unique features and uncovering potential strategies to sustain haematopoiesis during an extended lifetime.


Assuntos
Envelhecimento , Ratos-Toupeira , Animais , Humanos , Longevidade , Camundongos
6.
J Zoo Wildl Med ; 53(2): 357-362, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35758577

RESUMO

A prospective, descriptive study was conducted to evaluate the safety and efficacy of a field-ready anesthetic drug combination of medetomidine-ketamine-buprenorphine for data logger implantation surgery or recheck in free-ranging Cape dune (Bathyergus suillus: n = 41) and Cape (Georychus capensis: n = 37) mole-rats. All anesthesia data were reported as mean (±standard deviation). Medetomidine-ketamine-buprenorphine doses were 0.1 (±0.03), 10.6 (±2.8), and 0.06 (±0.03) mg/kg, respectively, for Cape dune mole-rats; and 0.2 (±0.03), 19.4 (±4.0), and 0.14 (±0.03) mg/kg, respectively, for Cape mole-rats. Induction was calm and took 2.00 (range: 1.00-6.00) min for the Cape dune and 1.75 (range 1.25 to 8.16) min for Cape mole-rats. A surgical plane of anesthesia was achieved in most Cape dune mole-rats (92%) and Cape mole-rats (90%). The remainder required supplementation with a single intramuscular injection of ketamine (3-9 mg/kg) during surgery. Heart and respiratory rates were 149 (±37) beats and 24 (±8) breaths per minute, respectively, for Cape dune mole-rats and 179 (±40) beats and 25 (±10) and breaths per minute, respectively for Cape mole-rats. Surgical time for mole-rats ranged from 25 to 38 min. Recovery was calm and took 8.50 (range: 2.00-19.00) min for Cape dune mole-rats and 9.75 (range: 2.00-34.00) min for Cape mole-rats to recover. For recovery, atipamezole was administered intramuscularly at 0.5 (±0.15) mg/kg for Cape dune mole-rats and 1 (±0.15) mg/kg for Cape mole-rats. All mole-rats were returned to their original burrows within 48 h of recovery. The medetomidine-ketamine-buprenorphine combination induced a predictable, safe anesthesia in Cape dune and Cape mole-rats suitable for short intraabdominal surgery. This combination is suited to in situ studies where the use of a formal surgery or laboratory is not feasible.


Assuntos
Anestesia , Buprenorfina , Ketamina , Anestesia/veterinária , Animais , Ketamina/farmacologia , Medetomidina/farmacologia , Ratos-Toupeira , Estudos Prospectivos
7.
Commun Biol ; 5(1): 526, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650336

RESUMO

Life underground has constrained the evolution of subterranean mammals to maximize digging performance. However, the mechanisms modulating morphological change and development of fossorial adaptations in such taxa are still poorly known. We assessed the morpho-functional diversity and early postnatal development of fossorial adaptations (bone superstructures) in the appendicular system of the African mole-rats (Bathyergidae), a highly specialized subterranean rodent family. Although bathyergids can use claws or incisors for digging, all genera presented highly specialized bone superstructures associated with scratch-digging behavior. Surprisingly, Heterocephalus glaber differed substantially from other bathyergids, and from fossorial mammals by possessing a less specialized humerus, tibia and fibula. Our data suggest strong functional and developmental constraints driving the selection of limb specializations in most bathyergids, but more relaxed pressures acting on the limbs of H. glaber. A combination of historical, developmental and ecological factors in Heterocephalus are hypothesized to have played important roles in shaping its appendicular phenotype.


Assuntos
Aclimatação , Ratos-Toupeira , Adaptação Fisiológica , Animais , Fenótipo
8.
Elife ; 112022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35674717

RESUMO

On the social scale, the blind mole rat (BMR; Spalax ehrenbergi) is an extreme. It is exceedingly solitary, territorial, and aggressive. BMRs reside underground, in self-excavated tunnels that they rarely leave. They possess specialized sensory systems for social communication and navigation, which allow them to cope with the harsh environmental conditions underground. This review aims to present the blind mole rat as an ideal, novel neuroethological model for studying aggressive and solitary behaviors. We discuss the BMR's unique behavioral phenotype, particularly in the context of 'anti-social' behaviors, and review the available literature regarding its specialized sensory adaptations to the social and physical habitat. To date, the neurobiology of the blind mole rat remains mostly unknown and holds a promising avenue for scientific discovery. Unraveling the neural basis of the BMR's behavior, in comparison to that of social rodents, can shed important light on the underlying mechanisms of psychiatric disorders in humans, in which similar behaviors are displayed.


Assuntos
Metabolismo Basal , Ratos-Toupeira , Animais , Humanos
9.
Artigo em Inglês | MEDLINE | ID: mdl-35731263

RESUMO

The naked mole rat has unique biologic characteristics that include atypical inflammatory responses. Lipopolysaccharide induces inflammation which triggers brain centers controlling feeding, and behavior to result in "sick animal behavior". We characterized the bodyweight, locomotor, and other behavioral responses of this rodent to lipopolysaccharide administration. Lipopolysaccharide caused weight losses, which were not prevented by TAK 242. In the open field test, lipopolysaccharide did not depress locomotion, while urination, defecation, and activity freezing were rare. The animals exhibited walling but not rearing and fast backward movements that were unaffected by lipopolysaccharide. Failure to depress locomotion suggests either a unique immunity-brain crosstalk or motor responses/centers that tolerate depressive effects of inflammation. The absence of activity freezing and rarity of urination and defecation suggests that novel environments or lipopolysaccharide do not induce anxiety, or that anxiety is expressed differently in the animal. The absence of rearing could be due to the design of the animal's locomotor apparatus while fast backward movement could be a mechanism for quick escape from threats in the tunnels of their habitat. Our results elucidate the unique biology of this rodent, which elicits interest in the animal as a model for inflammatory research, although the findings require mechanistic corroborations.


Assuntos
Lipopolissacarídeos , Ratos-Toupeira , Animais , Peso Corporal , Inflamação/induzido quimicamente , Lipopolissacarídeos/farmacologia , Locomoção , Ratos-Toupeira/fisiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-35710053

RESUMO

Evolutionary medicine has been a fast-growing field of biological research in the past decade. One of the strengths of evolutionary medicine is to use non-traditional model organisms which often exhibit unusual characteristics shaped by natural selection. Studying these unusual traits could provide valuable insight to understand biomedical questions, since natural selection likely discovers solutions to those complex biological problems. Because of many unusual traits, the naked mole-rat (NMR) has attracted attention from different research areas such as aging, cancer, and hypoxia- and hypercapnia-related disorders. However, such uniqueness of NMR physiology may sometimes make the translational study to human research difficult. Damaraland mole-rat (DMR) shares multiple characteristics in common with NMR, but shows higher degree of similarity with human in some aspects of their physiology. Research on DMR could therefore offer alternative insights and might bridge the gap between experimental findings from NMR to human biomedical research. In this review, we discuss studies of DMR as an extension of the current set of model organisms to help better understand different aspects of human biology and disease. We hope to encourage researchers to consider studying DMR together with NMR. By studying these two similar but evolutionarily distinct species, we can harvest the power of convergent evolution and avoid the potential biased conclusions based on life-history of a single species.


Assuntos
Envelhecimento , Ratos-Toupeira , Animais , Humanos , Ratos-Toupeira/fisiologia
11.
Biochim Biophys Acta Bioenerg ; 1863(7): 148582, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35667393

RESUMO

Naked mole-rats (NMR) and Damaraland mole-rats (DMR) exhibit extraordinary longevity for their body size, high tolerance to hypoxia and oxidative stress and high reproductive output; these collectively defy the concept that life-history traits should be negatively correlated. However, when life-history traits share similar underlying physiological mechanisms, these may be positively associated with each other. We propose that one such potential common mechanism might be the bioenergetic properties of mole-rats. Here, we aim to characterize the bioenergetic properties of two African mole-rats. We adopted a top-down perspective measuring the bioenergetic properties at the organismal, cellular, and molecular level in both species and the biological significance of these properties were compared with the same measures in Siberian hamsters and C57BL/6 mice, chosen for their similar body size to the mole-rat species. We found mole-rats shared several bioenergetic properties that differed from their comparison species, including low basal metabolic rates, a high dependence on glycolysis rather than on oxidative phosphorylation for ATP production, and low proton conductance across the mitochondrial inner membrane. These shared mole-rat features could be a result of evolutionary adaptation to tolerating variable oxygen atmospheres, in particular hypoxia, and may in turn be one of the molecular mechanisms underlying their extremely long lifespans.


Assuntos
Mitocôndrias , Ratos-Toupeira , Animais , Hipóxia , Camundongos , Camundongos Endogâmicos C57BL , Ratos-Toupeira/fisiologia , Respiração
12.
RNA ; 28(8): 1128-1143, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35654483

RESUMO

Paraspeckles are mammalian-specific nuclear bodies built on the long noncoding RNA NEAT1_2 The molecular mechanisms of paraspeckle formation have been mainly studied using human or mouse cells, and it is not known if the same molecular components are involved in the formation of paraspeckles in other mammalian species. We thus investigated the expression pattern of NEAT1_2 in naked mole-rats (nNEAT1_2), which exhibit extreme longevity and lower susceptibility to cancer. In the intestine, nNEAT1_2 is widely expressed along the entire intestinal epithelium, which is different from the expression of mNeat1_2 that is restricted to the cells of the distal tip in mice. Notably, the expression of FUS, a FET family RNA binding protein, essential for the formation of paraspeckles both in humans and mice, was absent in the distal part of the intestinal epithelium in naked mole-rats. Instead, mRNAs of other FET family proteins EWSR1 and TAF15 were expressed in the distal region. Exogenous expression of these proteins in Fus-deficient murine embryonic fibroblast cells rescued the formation of paraspeckles. These observations suggest that nNEAT1_2 recruits a different set of RNA binding proteins in a cell type-specific manner during the formation of paraspeckles in different organisms.


Assuntos
Paraspeckles , RNA Longo não Codificante , Animais , Humanos , Mucosa Intestinal/metabolismo , Camundongos , Ratos-Toupeira/genética , Ratos-Toupeira/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/genética
13.
EMBO J ; 41(15): e109694, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35694726

RESUMO

Naked mole rats (NMRs) are the longest-lived rodents yet their stem cell characteristics remain enigmatic. Here, we comprehensively mapped the NMR hematopoietic landscape and identified unique features likely contributing to longevity. Adult NMRs form red blood cells in spleen and marrow, which comprise a myeloid bias toward granulopoiesis together with decreased B-lymphopoiesis. Remarkably, youthful blood and marrow single-cell transcriptomes and cell compositions are largely maintained until at least middle age. Similar to primates, the primitive stem and progenitor cell (HSPC) compartment is marked by CD34 and THY1. Stem cell polarity is seen for Tubulin but not CDC42, and is not lost until 12 years of age. HSPC respiration rates are as low as in purified human stem cells, in concert with a strong expression signature for fatty acid metabolism. The pool of quiescent stem cells is higher than in mice, and the cell cycle of hematopoietic cells is prolonged. By characterizing the NMR hematopoietic landscape, we identified resilience phenotypes such as an increased quiescent HSPC compartment, absence of age-related decline, and neotenic traits likely geared toward longevity.


Assuntos
Envelhecimento , Ratos-Toupeira , Adulto , Envelhecimento/metabolismo , Animais , Hematopoese , Humanos , Camundongos , Pessoa de Meia-Idade , Ratos-Toupeira/genética , Ratos-Toupeira/metabolismo , Fenótipo , Células-Tronco
14.
Artigo em Inglês | MEDLINE | ID: mdl-35537667

RESUMO

Sub-lethal effects, such as oxidative stress, can be linked to various breeding and thermophysiological strategies, which themselves can be linked to seasonal variability in abiotic factors. In this study, we investigated the subterranean, social living Natal mole-rat (Cryptomys hottentotus natalensis), which, unlike other social mole-rat species, implements heterothermy seasonally in an attempt to avoid exercise-induced hyperthermia and relies solely on behavioural reproductive suppression to maintain reproductive skew in colonies. Subsequently, we investigated how oxidative stress varied between season, sex and breeding status in Natal mole-rats. Oxidative markers included total oxidant status (TOS measure of total peroxides present), total antioxidant capacity (TAC), OSI (oxidative stress index) and malondialdehyde (MDA) to measure oxidative stress. Breeding and non-breeding mole-rats of both sexes were captured during the summer (wet season) and winter (dry season). Seasonal environmental variables (air temperature, soil temperature and soil moisture) had a significant effect on TOS, OSI and MDA, where season affected each sex differently. Unlike other social mole-rat species that use both physiological and behavioural means of reproductive suppression, no oxidative costs to reproduction were present in the Natal mole-rats. Males had significantly higher MDA than females, which was most apparent in summer (wet season). We conclude that the significant oxidative damage in males is a consequence of exercise-induced oxidative stress, exacerbated by increased burrow humidities and poorer heat dissipation abilities as a function of body mass. This study highlights the importance of both breeding and thermophysiological strategies in affecting oxidative stress.


Assuntos
Ratos-Toupeira , Reprodução , Animais , Feminino , Masculino , Ratos-Toupeira/fisiologia , Estresse Oxidativo , Reprodução/fisiologia , Comportamento Sexual Animal/fisiologia , Solo
16.
Aging (Albany NY) ; 14(9): 3728-3756, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507806

RESUMO

Naked mole-rats (NMR) are subterranean rodents characterized by an unusual longevity coupled with an unexplained resistance to aging. In the present study, we performed extensive in situ analysis and single-cell RNA-sequencing comparing young and older animals. At variance with other species, NMR exhibited a striking stability of skin compartments and cell types, which remained stable over time without aging-associated changes. Remarkably, the number of stem cells was constant throughout aging. We found three classical cellular states defining a unique keratinocyte differentiation trajectory that were not altered after pseudo-temporal reconstruction. Epidermal gene expression did not change with aging either. Langerhans cell clusters were conserved, and only a higher basal stem cell expression of Igfbp3 was found in aged animals. In accordance, NMR skin healing closure was similar in young and older animals. Altogether, these results indicate that NMR skin is characterized by peculiar genetic and cellular features, different from those previously demonstrated for mice and humans. The remarkable stability of the aging NMR skin transcriptome likely reflects unaltered homeostasis and resilience.


Assuntos
Ratos-Toupeira , Transcriptoma , Envelhecimento/genética , Animais , Longevidade/genética , Camundongos , Ratos-Toupeira/genética , Células-Tronco
17.
Int J Mol Sci ; 23(9)2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35563075

RESUMO

Peptidylarginine deiminases (PADs) and extracellular vesicles (EVs) may be indicative biomarkers of physiological and pathological status and adaptive responses, including to diseases and disorders of the central nervous system (CNS) and related to hypoxia. While these markers have been studied in hypoxia-intolerant mammals, in vivo investigations in hypoxia-tolerant species are lacking. Naked mole-rats (NMR) are among the most hypoxia-tolerant mammals and are thus a good model organism for understanding natural and beneficial adaptations to hypoxia. Thus, we aimed to reveal CNS related roles for PADs in hypoxia tolerance and identify whether circulating EV signatures may reveal a fingerprint for adaptive whole-body hypoxia responses in this species. We found that following in vivo acute hypoxia, NMR: (1) plasma-EVs were remodelled, (2) whole proteome EV cargo contained more protein hits (including citrullinated proteins) and a higher number of associated KEGG pathways relating to the total proteome of plasma-EVs Also, (3) brains had a trend for elevation in PAD1, PAD3 and PAD6 protein expression, while PAD2 and PAD4 were reduced, while (4) the brain citrullinome had a considerable increase in deiminated protein hits with hypoxia (1222 vs. 852 hits in normoxia). Our findings indicate that circulating EV signatures are modified and proteomic content is reduced in hypoxic conditions in naked mole-rats, including the circulating EV citrullinome, while the brain citrullinome is elevated and modulated in response to hypoxia. This was further reflected in elevation of some PADs in the brain tissue following acute hypoxia treatment. These findings indicate a possible selective role for PAD-isozymes in hypoxia response and tolerance.


Assuntos
Vesículas Extracelulares , Proteômica , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Vesículas Extracelulares/metabolismo , Hipóxia/metabolismo , Ratos-Toupeira/metabolismo , Desiminases de Arginina em Proteínas/metabolismo , Proteoma/metabolismo
18.
Horm Behav ; 143: 105196, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35597054

RESUMO

Despite decades of research into the evolutionary drivers of sociality, we know relatively little about the underlying proximate mechanisms. Here we investigate the potential role of prolactin in the highly social naked mole-rat. Naked mole-rats live in large social groups but, only a small number of individuals reproduce. The remaining non-breeders are reproductively suppressed and contribute to burrow maintenance, foraging, and allo-parental care. Prolactin has well-documented links with reproductive timing and parental behaviour, and the discovery that non-breeding naked mole-rats have unusually high prolactin levels has led to the suggestion that prolactin may help maintain naked mole-rat sociality. To test this idea, we investigated whether urinary prolactin was correlated with cooperative behaviour and aggression. We then administered the prolactin-suppressing drug Cabergoline to eight female non-breeders for eight weeks and assessed the physiology and behaviour of the animals relative to controls. Contrary to the mammalian norm, and supporting previous findings for plasma, we found non-breeders had elevated urinary prolactin concentrations that were similar to breeding females. Further, prolactin levels were higher in heavier, socially dominant non-breeders. Urinary prolactin concentrations did not explain variation in working behaviour or patterns of aggression. Furthermore, females receiving Cabergoline did not show any behavioural or hormonal (progesterone) differences, and urinary prolactin did not appear to be suppressed in individuals receiving Cabergoline. While the results add to the relatively limited literature experimentally manipulating prolactin to investigate its role in reproduction and behaviour, they fail to explain why prolactin levels are high in non-breeding naked mole-rats, or how female non-breeding phenotypes are maintained.


Assuntos
Ratos-Toupeira , Prolactina , Animais , Cabergolina , Feminino , Ratos-Toupeira/fisiologia , Reprodução/fisiologia , Comportamento Social
19.
Open Biol ; 12(4): 210292, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35382566

RESUMO

Naked mole-rats (NM-R; Heterocephalus glaber) live in multi-generational colonies with a social hierarchy, and show low cancer incidence and long life-spans. Here we asked if an immune component might underlie such extreme physiology. The largest lymphoid organ is the spleen, which plays an essential role in responding 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 NM-Rs. Spleen size in healthy NM-Rs showed considerable inter-individual variability, with some animals displaying enlarged spleens. In all healthy NM-Rs, the spleen is a major site of adult haematopoiesis under normal physiological conditions. However, myeloid-to-lymphoid cell ratio is increased and splenic marginal zone showed markedly altered morphology when compared to other rodents. Healthy NM-Rs with enlarged spleens showed potentially better anti-microbial profiles and were much more likely to have a high rank within the colony. We propose that the anatomical plasticity of the spleen might be regulated by social interaction and gives immunological advantage to increase the lifespan of higher-ranked animals.


Assuntos
Ratos-Toupeira , Baço , Envelhecimento , Animais , Longevidade , Ratos-Toupeira/anatomia & histologia , Ratos-Toupeira/genética , Análise de Sequência de RNA
20.
Genome Biol Evol ; 14(5)2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35482036

RESUMO

The molecular mechanisms of aging and life expectancy have been studied in model organisms with short lifespans. However, long-lived species may provide insights into successful strategies for healthy aging, potentially opening the door for novel therapeutic interventions in age-related diseases. Notably, naked mole-rats, the longest-lived rodent, present attenuated aging phenotypes compared with mice. Their resistance toward oxidative stress has been proposed as one hallmark of their healthy aging, suggesting their ability to maintain cell homeostasis, specifically their protein homeostasis. To identify the general principles behind their protein homeostasis robustness, we compared the aggregation propensity and mutation tolerance of naked mole-rat and mouse orthologous proteins. Our analysis showed no proteome-wide differential effects in aggregation propensity and mutation tolerance between these species, but several subsets of proteins with a significant difference in aggregation propensity. We found an enrichment of proteins with higher aggregation propensity in naked mole-rat, and these are functionally involved in the inflammasome complex and nucleic acid binding. On the other hand, proteins with lower aggregation propensity in naked mole-rat have a significantly higher mutation tolerance compared with the rest of the proteins. Among them, we identified proteins known to be associated with neurodegenerative and age-related diseases. These findings highlight the intriguing hypothesis about the capacity of the naked mole-rat proteome to delay aging through its proteomic intrinsic architecture.


Assuntos
Agregados Proteicos , Proteômica , Animais , Longevidade/genética , Camundongos , Ratos-Toupeira/genética , Mutação , Proteoma/genética
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