Suppression of neurons in circumventricular organs enables months-long survival without water in thirteen-lined ground squirrels
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PROVIDER: PRJNA1093053 | ENA |
REPOSITORIES: ENA
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Project description:Water deprivation is a life-threatening condition that engages a protective physiological response to couple osmolyte retention with potentiation of thirst. This response, typical for most mammals, safeguards against short-term water deprivation, but fails in the long-term. Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) employ the short-term response during summer, whereas during winter they lack thirst and survive without water for months. Here, we show that long-term thirst suppression occurs despite hormonal and behavioral signs of a dramatic fluid deficit and originates from hypoactivity of neurons in the circumventricular organs, which exhibit marked functional suppression during winter that blunts their sensitivity to thirst cues. Our work reveals a remarkable capacity of the evolutionarily conserved brain regions which control fluid homeostasis in mammals to enable long-term survival without water.
2024-11-28 | GSE262723 | GEO
Project description:Mitochondrial microRNA profiles are altered in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) during hibernation
| PRJNA1069040 | ENA
Project description:Hibernating mammals undergo a dramatic drop in temperature and blood flow during torpor and must suppress hemostasis to avoid stasis blood clotting. In addition, cold storage of most mammalian platelets induces cold storage lesions, resulting in rapid clearance following transfusion. 13-lined ground squirrels (Ictidomys tridecemlineatus) provide a model to study hemostasis and cold storage of platelets during hibernation because, even with a body temperature of 4-8C, their platelets are resistant to cold storage lesions. We quantified and systematically compared proteomes of platelets collected from ground squirrels at summer (activity), fall (entrance), and winter (topor) to elucidate how molecular-level changes in platelets may support hemostatic adaptations in torpor. Platelets were isolated from squirrel blood collected in June, October, and January. Platelet lysates from each animal were digested with trypsin prior to 11-plex tandem mass tag (TMT) labeling, followed by LC-MS/MS analysis for relative protein quantification. We found over 700 platelet proteins with significant changes over the course of entrance, torpor, and activity – including systems of proteins regulating translation, platelet degranulation, metabolism, complement, and coagulation cascades. We also noted species specific differences in hemostatic, secretory, and inflammatory regulators in ground squirrel platelets relative to human platelets. In addition to providing the first ever proteomic characterization of platelets from hibernating animals, our results support a model whereby systematic changes in metabolic, hemostatic, and other proteins support physiological adaptations in torpor. In addition, our results could translate into better methods to cold store human platelets, increasing their supply and quality for transfusions.
2021-12-08 | PXD026903 | Pride
Project description:Hibernators dramatically lower metabolism to save energy while fasting for months. Prolonged fasting challenges metabolic homeostasis, yet small-bodied hibernators emerge each spring ready to resume all aspects of active life, including immediate reproduction. The liver is the body’s metabolic hub, processing and detoxifying macromolecules to provide essential fuels to brain, muscle and other organs throughout the body. Here we quantify changes in liver gene expression using RNA-seq to measure the steady-state transcriptome and GRO-seq to measure transcription across several distinct physiological states of hibernation in 13-lined ground squirrels. Our data capture key timepoints in both the seasonal and torpor-arousal cycles of hibernation. Strong positive correlation between transcription and the transcriptome indicates that transcriptional control dominates the known seasonal reprogramming of metabolic gene expression in liver for hibernation. During the torpor-arousal cycle, however, discordance develops between transcription and the steady-state transcriptome by at least two mechanisms: 1) although not transcribed during torpor, some liver transcripts are unusually stable, consistent with data from other tissues; and 2) unexpectedly, on some genes, we document continuing, slow elongation with a failure to terminate transcription across the torpor bout. While the steady-state RNAs corresponding to these readthrough transcripts did not increase during torpor, they did increase shortly after rewarming despite then low transcription. Both of these mechanisms assure the availability of functional transcripts immediately upon rewarming. Integration of transcriptional, post-transcriptional and RNA stability control mechanisms, all demonstrated in these data, likely initiate a serial gene expression program across the short euthermic period that restores the tissue and prepares the animal for the next bout of torpor.
2021-05-10 | GSE166370 | GEO
Project description:Thirteen-lined ground squirrels (TLGS) are obligate hibernators that cycle between torpor (low metabolic rate and body temperature) and interbout euthermia (IBE; typical euthermic body temperature and metabolism) from late autumn to spring. Many physiological changes occur throughout hibernation, including a reduction in liver mitochondrial metabolism during torpor, which is reversed during arousal to interbout euthermia. Nuclear-encoded microRNA (small post-transcriptional regulator molecules) differ in abundance throughout TLGS hibernation and have been shown to regulate mitochondrial gene expression in mammalian cell culture (where they are referred to as mitomiRs). This study characterized differences in mitomiR profiles from TLGS liver mitochondria isolated during summer, torpor, and IBE, and predicted their mitochondrial targets. Using small RNA sequencing, differentially abundant mitomiRs were identified between hibernation states and, using qPCR analysis we quantified expression of predicted mitochondrial mRNA targets. Most differences in mitomiR abundances were seasonal (i.e. between summer and winter) with only one mitomiR differentially abundant between IBE and torpor. Multiple factor analysis revealed unique clustering of hibernation states, predominantly driven by mitomiR abundances, and nine of these differentially abundant mitomiRs had predicted mitochondrial RNA targets, including subunits of electron transfer system complexes I and IV, 12S rRNA and two tRNAs. Overall, mitomiRs were predicted to suppress expression of their mitochondrial targets and may have some involvement in regulating protein translation in mitochondria. This study found differences in mitomiR abundances between seasons and hibernation states of TLGS and suggests potential mechanisms in regulating the mitochondrial electron transfer system.
2024-07-31 | GSE254223 | GEO
Project description:GRO-seq analysis of liver gene transcription in hibernating 13-lined ground squirrels
| PRJNA700632 | ENA
Project description:Mammalian hibernation is characterized by metabolic rate depression and a strong decrease in core body temperature that together create energy savings such that most species do not have to eat over the winter months. Brown adipose tissue (BAT), a thermogenic tissue that uses uncoupled mitochondrial respiration to generate heat instead of ATP, plays a major role in rewarming from deep torpor. The present study used label-free phosphoproteomics to investigate changes in BAT from thirteen-lined ground squirrels (Ictidomys tridecemlineatus), comparing euthermic squirrels with squirrels in deep torpor. Differential expression of mitochondrial proteins was also investigated. Surprisingly, mitochondrial membrane and matrix protein expression in BAT was largely constant between active euthermic squirrels and their hibernating counterparts. Validation by immunoblotting confirmed that the protein levels of mitochondrial respiratory chain complexes were largely unchanged. However, phosphoproteomics showed that pyruvate dehydrogenase (PDH) phosphorylation increased during ground squirrel hibernation, and this was confirmed by immunoblotting with phospho-specific antibodies. PDH phosphorylation leads to its inactivation, which suggests that BAT carbohydrate oxidation is inhibited during hibernation. Phosphorylation of hormone-sensitive lipase (HSL) also increased during hibernation, suggesting that HSL would be in a partly activated state in BAT to produce the fatty acids that are likely the primary fuel for thermogenesis during arousal.
2017-07-11 | PXD004261 | Pride
Project description:Kidney gene expression dynamics during torpor-arousal cycles in hibernating 13-lined ground squirrels
| PRJNA943230 | ENA
Project description:PurposeThe cone-dominant, 13-lined ground squirrel (13-LGS) retina mimics the human central retina, but a thorough examination of retinal development in this species has not been reported. Here, the embryonic and postnatal development of the 13-LGS retina was studied to further characterize 13-LGS as a practical alternative animal model for investigating cone-based vision in health and disease.MethodsThe spatiotemporal expression of key progenitor and cell type markers was examined in retinas from defined embryonic and postnatal stages using immunohistochemistry. Postnatal gene expression changes were validated by quantitative PCR.ResultsThe 13-LGS neuroblastic layer expressed key progenitor markers (Sox2, Vsx2, Pax6, and Lhx2) at E18. Sequential cell fate determination evidenced by the first appearance of cell-type-specific marker labeling was at embryonic stage 18 (E18) with ganglion cells (Brn-3A, HuC/D) and microglia (Iba1); at E22.5 with photoreceptor progenitors (Otx2, recoverin) followed shortly by horizontal and amacrine cells (Lhx1, Oc1) at E24 to E25.5; and at postnatal stage 15 (P15) with bipolar cells (Vsx1, CaBP5) and Müller glia cells (GS, Rlbp1). Photoreceptor maturation indicated by opsin-positive outer segments and peanut agglutinin (PNA) labeling of cone sheaths was completed at the time of eye opening (P21-P24).ConclusionsThe timeline and order of retinal cell development in the 13-LGS generally matches that recorded from other mammalian models but with a stark variation in the proportion of various cell types due to cone-dense photoreceptors.Translational relevanceThis thorough examination of an emerging translationally relevant cone-dominant specie provides a baseline for future disease modeling and stem cell approach studies of human vision.
| S-EPMC9695149 | biostudies-literature
Project description:Hibernating mammals undergo a dramatic drop in temperature and blood flow during torpor, yet avoid stasis blood clotting through mechanisms that remain unspecified. The effects of hibernation on hemostasis are especially complex, as cold temperatures generally activate platelets, resulting in platelet clearance and cold storage lesions in the context of blood transfusion. With a hibernating body temperature of 4°C-8°C, 13-lined ground squirrels (Ictidomys tridecemlineatus) provide a model to study hemostasis as well as platelet cold storage lesion resistance during hibernation. Here, we quantified and systematically compared proteomes of platelets collected from ground squirrels at summer (active), fall (entrance), and winter (topor) to elucidate how molecular-level changes in platelets may support hemostatic adaptations in torpor. Platelets were isolated from a total of 11 squirrels in June, October, and January. Platelet lysates from each animal were digested with trypsin prior to 11-plex tandem mass tag (TMT) labeling, followed by LC-MS/MS analysis for relative protein quantification. We measured >700 proteins with significant variations in abundance in platelets over the course of entrance, torpor, and activity-including systems of proteins regulating translation, secretion, metabolism, complement, and coagulation cascades. We also noted species-specific differences in levels of hemostatic, secretory, and inflammatory regulators in ground squirrel platelets relative to human platelets. Altogether, we provide the first ever proteomic characterization of platelets from hibernating animals, where systematic changes in metabolic, hemostatic, and other proteins may account for physiological adaptations in torpor and also inform translational effort to improve cold storage of human platelets for transfusion.
| S-EPMC8616595 | biostudies-literature