More Like this

1. Is the Mole Rat Vomeronasal Organ Functional?

   https://doi.org/10.1002/ar.24060  

   Dennis, John_C; Stilwell, Natalie_K; Smith, Timothy_D; Park, Thomas_J; Bhatnagar, Kunwar_P; Morrison, Edward_E (January 2019, The Anatomical Record)

   ABSTRACT The colonial naked mole ratHeterocephalus glaberis a subterranean, eusocial rodent. TheH. glabervomeronasal organ neuroepithelium (VNE) displays little postnatal growth. However, the VNE remains neuronal in contrast to some mammals that possess nonfunctional vomeronasal organ remnants, for example, catarrhine primates and some bats. Here, we describe the vomeronasal organ (VNO) microanatomy in the naked mole rat and we make preliminary observations to determine ifH. glabershares its minimal postnatal VNE growth with other African mole rats. We also determine the immunoreactivity to the mitotic marker Ki67, growth‐associated protein 43 (GAP43), and olfactory marker protein (OMP) in six adult and three subadultH. glaberindividuals. VNE volume measurements on a small sample ofCryptomys hottentotusandFukomys damarensisindicate that the VNE of those African mole rat species are also likely to be growth‐deficient. Ki67(+) cells show that the sensory epithelium is mitotically active. GAP43 labelling indicates neurogenesis and OMP(+) cells are present though less numerous compared to GAP43(+) cells. In this respect, the VNO ofH. glaberdoes not appear vestigial. The African mole rat VNE may be unusually variable, perhaps reflecting reduced selection pressure on the vomeronasal system. If so, African mole rats may provide a useful genetic model for understanding the morphological variability observed in the mammalian VNO. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 303:318–329, 2020. © 2019 American Association for Anatomy 

   more » « less
2. Life without substance P: The naked mole rat

   https://doi.org/10.1016/B978-0-443-22194-1.00013-6  

   Zhao, Aishi; Lee, Jiwon; Gryszkiewicz, Weronika; Park, Thomas J (January 2025, Elsevier)

   Vink, Robert (Ed.)

   The African naked mole rat (Heterocephalus glaber) is a small, eusocial rodent that lives in large colonies consisting of up to 295 individuals. Their skin is pink and translucent, and naked mole rats have a distinct set of incisors that protrude externally from the mouth so that they can close their lips behind their teeth while using the teeth to dig tunnels, toilets, and nest chambers. They construct and inhabit complex underground tunnel systems in the Horn of Africa where they are protected from climate extremes and predators on the surface, but still face limited resources (sparsely distributed food), and a biologically challenging environment where there is a depletion of oxygen and an accumulation of carbon dioxide from many respirating individuals living in an unventilated space. This is particularly an issue in the communal nest chambers where animals gather to huddle and sleep. Data from Zions et al. show that the nest chambers in colonies of captive naked mole rats have significantly, and substantially higher concentrations of CO2 compared to other compartments in the housing system. They also showed that on average, colony members spent more than 70% of their time in the nest chamber, exposed to elevated CO2. Naked mole rats have a multitude of biological adaptations that make them specialized for life in humid, congested, poorly ventilated burrows. Subsequently, this species is a fascinating and important nontraditional model for biomedical research. Studies have focused on topics such as tolerance to hypoxia and hypercapnia, extreme longevity, resistance to cancer, and insensitivity to chemical pain. One remarkable feature that naked mole rats display is the lack of Substance P from their peripheral nerves. Substance P is associated with pain from a variety of irritants such as carbon dioxide (CO2), acid, capsaicin, and ammonia, as well as itch-like pruritogen, like histamines. Lack of Substance P is presumably an adaptation to reduce the negative effects of living in a high CO2 atmosphere, which would cause a burning sensation in the nasal cavity and around the eyes, as well as acidosis in the lungs that causes pulmonary edema. This chapter reviews how this feature affects their physiology and behavior. For example, naked mole rats show a blunted response to inflammatory pain, complete insensitivity to irritants such as capsaicin, ammonia, and acid, and they do not show a scratching response to histamine. 

   more » « less
3. Epigenetic aging of the demographically non-aging naked mole-rat

   https://doi.org/10.1038/s41467-022-27959-9  

   Kerepesi, Csaba; Meer, Margarita V.; Ablaeva, Julia; Amoroso, Vince G.; Lee, Sang-Goo; Zhang, Bohan; Gerashchenko, Maxim V.; Trapp, Alexandre; Yim, Sun Hee; Lu, Ake T.; et al (December 2022, Nature Communications)

   Abstract The naked mole-rat (NMR) is an exceptionally long-lived rodent that shows no increase of mortality with age, defining it as a demographically non-aging mammal. Here, we perform bisulfite sequencing of the blood of > 100 NMRs, assessing > 3 million common CpG sites. Unsupervised clustering based on sites whose methylation correlates with age reveals an age-related methylome remodeling, and we also observe a methylome information loss, suggesting that NMRs age. We develop an epigenetic aging clock that accurately predicts the NMR age. We show that these animals age much slower than mice and much faster than humans, consistent with their known maximum lifespans. Interestingly, patterns of age-related changes of clock sites in Tert and Prpf19 differ between NMRs and mice, but there are also sites conserved between the two species. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species. 

   more » « less
4. Not just a cousin of the naked mole-rat: Damaraland mole-rats offer unique insights into biomedicine

   https://doi.org/10.1016/j.cbpb.2022.110772  

   Wong, Hoi-Shan; Freeman, David A.; Zhang, Yufeng (October 2022, Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology)
5. Pharmacokinetics of Injectable Meloxicam and Buprenorphine in the Naked Mole-Rat (Heterocephalus glaber)

   Moran, CR; Park, TJ; Buffenstein, R; Chakrabarty, S; Lindeblad, MO; Fortman, JD; Adams, CR (July 2024, Journal of the American Association for Laboratory Animal Science)

   Unique characteristics of the naked mole-rat (NMR) have made it increasingly popular as a laboratory animal model. These rodents are used to study many fields of research including longevity and aging, cancer, circadian rhythm, pain, and metabolism. Currently, the analgesic dosing regimens used in the NMR mirror those used in other rodent species. However, there is no pharmacokinetic (PK) data supporting the use of injectable analgesics in the NMR. Therefore, we conducted two independent PK studies to evaluate two commonly used analgesics in the NMR; meloxicam (2 mg/kg SC) and buprenorphine (0.1 mg/kg SC). In each study, blood was collected at 8 time points after subcutaneous injection of meloxicam or buprenorphine (0 (pre-dose), 0.25, 0.5, 1, 2, 4, 8, and 24 hrs). Three NMRs were used per time point for a total of 24 animals per PK study. Plasma concentrations of meloxicam were highest between 0.5 hrs and 1 hr post-injection. Levels remained above the extrapolated dog and cat therapeutic threshold levels (390-911 ng/mL) for at least 24 hrs. Plasma concentrations of buprenorphine were highest between 0.25 and 0.5 hrs post-injection. Levels remained above the human therapeutic threshold (1 ng/mL) for up to 21 hrs. No skin reactions were seen in association with injection of either drug. In summary, this data supports dosing meloxicam (2 mg/kg SC) once every 24 hrs and buprenorphine (0.1 mg/kg SC) once every 8-12 hrs in the NMR. Further studies should be performed to evaluate the clinical efficacy of these drugs by correlating plasma concentrations with post-operative pain assessments. 

   more » « less