Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters

Matos-Cruz, Vanessa; Schneider, Eve R.; Mastrotto, Marco; Merriman, Dana K.; Bagriantsev, Sviatoslav N.; Gracheva, Elena O.

doi:10.1016/j.celrep.2017.11.083

Cited by 75 publications

(79 citation statements)

References 32 publications

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“…These processes are energetically expensive, underscoring the notion that torpor is an active physiological process that requires molecular fine-tuning. Indeed, recent studies in hibernating rodents revealed profound genomically encoded changes in temperature sensors, mitochondrial function, protein control machineries, and cytoskeletal integrity [5, 6, 33]. We suggest the existence of other such modifications in various groups of enzymes, ion channels, and transporters implicated in energy homeostasis and ionic balance regulation.…”

Section: Discussionmentioning

confidence: 78%

“…We focused on thermoreceptors and nociceptors, which in squirrels and other rodents have a soma diameter of less than 30 mm (Figure 1B) [4–6]. To preserve state-specific properties, neurons were incubated at their respective physiological temperatures (37 C for active and 10 C for torpid neurons) prior to patch-clamp recordings at 20 C, the most commonly used temperature for electrophysiological recordings from DRG.…”

Section: Resultsmentioning

confidence: 99%

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Somatosensory Neurons Enter a State of Altered Excitability during Hibernation

et al. 2018

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SUMMARY Hibernation in mammals involves prolonged periods of inactivity, hypothermia, hypometabolism, and decreased somatosensation. Peripheral somatosensory neurons play an essential role in the detection and transmission of sensory information to CNS and in the generation of adaptive responses. During hibernation, when body temperature drops to as low as 2 C, animals dramatically reduce their sensitivity to physical cues [1, 2]. It is well established that, in non-hibernators, cold exposure suppresses energy production, leading to dissipation of the ionic and electrical gradients across the plasma membrane and, in the case of neurons, inhibiting the generation of action potentials [3]. Conceivably, such cold-induced elimination of electrogenesis could be part of a general mechanism that inhibits sensory abilities in hibernators. However, when hibernators become active, the bodily functions—including the ability to sense environmental cues—return to normal within hours, suggesting the existence of mechanisms supporting basal functionality of cells during torpor and rapid restoration of activity upon arousal. We tested this by comparing properties of somatosensory neurons from active and torpid thirteen-lined ground squirrels (Ictidomys tridecemlineatus). We found that torpid neurons can compensate for cold-induced functional deficits, resulting in unaltered resting potential, input resistance, and rheobase. Torpid neurons can generate action potentials but manifest markedly altered firing patterns, partially due to decreased activity of voltage-gated sodium channels. Our results provide insights into the mechanism that preserves somatosensory neu rons in a semi-active state, enabling fast restoration of sensory function upon arousal. These findings contribute to the development of strategies enabling therapeutic hypothermia and hypometabolism.

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Section: Discussionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Somatosensory Neurons Enter a State of Altered Excitability during Hibernation

et al. 2018

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“…Woolly mammoths (Mammuthus primigenius), in contrast, lived in the extreme cold of the mammoth-steppe where average winter temperatures ranged from −30° to −50°C (MacDonald et al, 2012). Cold adapted and artic species have evolved molecular and physiological adaptations to their circadian systems (Bloch et al, 2013;Lu et al), adipose biology (Fumagalli et al, 2015;Nelson et al, 2014;Welch et al, 2014), and temperature sensation (Matos-Cruz et al, 2017) to deal with serve cold and long periods of persistent dark in winter and light in summer, suggesting mammoths may have also evolved similar adaptations. While temperature sensation in mammals is a complex sensory process in which temperature-sensitive primary sensory neurons convey thermal information from the skin and peripheral organs to the CNS (Vriens et al, 2014), temperature-sensitive transient receptor potential (thermoTRP) cation channels are the major molecular thermosensors (MacDonald et al, 2012;Vriens et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Golden hamsters (Mesocricetus auratus) have TRPM8 channels with dramatically reduced cold sensitivity and do not avoid cold temperatures (Bloch et al, 2013;Lu et al;Matos-Cruz et al, 2017). TRPM8 is also activated in response to cold temperatures and ligands that induce cooling sensations such as menthol, eucalyptol, and the 'super-cooling' agent icilin in heterologous expression systems (Fumagalli et al, 2015;Nelson et al, 2014;Vriens et al, 2014;Welch et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…TRPM8 is also activated in response to cold temperatures and ligands that induce cooling sensations such as menthol, eucalyptol, and the 'super-cooling' agent icilin in heterologous expression systems (Fumagalli et al, 2015;Nelson et al, 2014;Vriens et al, 2014;Welch et al, 2014). Remarkably administration TRPM8 antagonists to mice and rats decreased their core body temperature, implicating TRPM8 in maintenance of body temperature in addition to cold sensation (Almeida et al, 2012;Gavva et al, 2012;Matos-Cruz et al, 2017;Reimúndez et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Relaxed constraint and thermal desensitization of the cold-sensing ion channel TRPM8 in mammoths

Chigurapati

Sulak

Miller

et al. 2018

Preprint

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Unlike the living elephants, which live in warm tropical and subtropical habitats, mammoths lived in extreme cold environments where average winter temperatures ranged from −30° to −50°C.Like other cold adapted and artic species, mammoths evolved of suite of morphological and molecular adaptations that facilitated life in the cold. Here we reanalyze mammoth genomes and find that genes with mammoth-specific amino acid substitutions are enriched in functions related to temperature sensation. Among the genes with mammoth-specific amino acid substitutions is TRPM8, which mediates sensitivity to nonnoxious cool temperatures from 25-28°C and cooling sensations induced by the chemical agonists menthol and icilin. We find that TRPM8 evolved rapidly in the mammoth stem-lineage, likely because of an episode of relaxed purifying selection. Functional characterization of resurrected mammoth and ancestral TRPM8 indicates that the mammoth TRPM8 is desensitized to cold but maintains sensitivity to menthol and icilin. These data suggest that as mammoths evolved into a cold tolerant species they lost the need for a cold-sensitive TRPM8.

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Temperature‐responsive hydrogel‐grafted vessel‐on‐a‐chip: Exploring cold‐induced endothelial injury

Shen,

Li,

She

et al. 2024

Biotech & Bioengineering

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Cold‐induced vasoconstriction is a significant contributor that leads to chilblains and hypothermia in humans. However, current animal models have limitations in replicating cold‐induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel‐on‐a‐chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of N‐isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature set at 30°C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37°C to 4°C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel‐on‐a‐chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel‐on‐a‐chip led to cell necrosis, mitochondrial membrane potential (ΔΨm) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold‐induced endothelial injury, this groundbreaking thermosensitive vessel‐on‐a‐chip technology offers promising advancements in the study of cold‐induced cardiovascular diseases, including pathogenesis and therapeutic drug screening.

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Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters

Cited by 75 publications

References 32 publications

Somatosensory Neurons Enter a State of Altered Excitability during Hibernation

Somatosensory Neurons Enter a State of Altered Excitability during Hibernation

Relaxed constraint and thermal desensitization of the cold-sensing ion channel TRPM8 in mammoths

Temperature‐responsive hydrogel‐grafted vessel‐on‐a‐chip: Exploring cold‐induced endothelial injury

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