Transient hypertension and sustained tachycardia in mice housed individually in metabolism cages

Hoppe, Chantal Christiana; Moritz, Karen M.; Fitzgerald, Sharyn M.; Bertram, John F.; Evans, Roger G.

doi:10.33549/physiolres.931390

Cited by 24 publications

(6 citation statements)

References 29 publications

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“…This effect has been shown in mice on a mixed C57BL/6 J/129/sv background, but in these mice, MAP did return to baseline following day 1 in the metabolic cages, with HR remaining elevated. 34 HR remained elevated in our study, and there was a significant interaction between time and genotype in the metabolic cages. Cosinor analysis was carried out on this dataset and showed that the robustness of HR (strength of the rhythm) was only ∼ 20% for both genotypes.…”

Section: Discussionsupporting

confidence: 53%

Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior

et al. 2023

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Brain and muscle ARNT-like 1 (BMAL1) is a core circadian clock protein and transcription factor that regulates many physiological functions, including blood pressure (BP). Male global Bmal1 knockout (KO) mice exhibit ∼10 mmHg reduction in BP, as well as a blunting of BP rhythm. The mechanisms of how BMAL1 regulates BP remains unclear. The adrenal gland synthesizes hormones, including glucocorticoids and mineralocorticoids, that influence BP rhythm. To determine the role of adrenal BMAL1 on BP regulation, adrenal-specific Bmal1 (ASCre/+::Bmal1) KO mice were generated using aldosterone synthase Cre recombinase to KO Bmal1 in the adrenal gland zona glomerulosa. We confirmed the localization and efficacy of the KO of BMAL1 to the zona glomerulosa. Male ASCre/+::Bmal1 KO mice displayed a shortened BP and activity period/circadian cycle (typically 24 hours) by ∼1 hour and delayed peak of BP and activity by ∼2 and 3 hours, respectively, compared with littermate Cre- control mice. This difference was only evident when KO mice were in metabolic cages, which acted as a stressor, as serum corticosterone was increased in metabolic cages compared with home cages. ASCre/+::Bmal1 KO mice also displayed altered diurnal variation in serum corticosterone. Furthermore, these mice have altered eating behaviors where they have a blunted night/day ratio of food intake, but no change in overall food consumed compared with controls. Overall, these data suggest that adrenal BMAL1 has a role in the regulation of BP rhythm and eating behaviors.

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Section: Discussionsupporting

confidence: 53%

Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior

et al. 2023

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“…Hydrophobic sand could be used for urine collection in the control cage and to investigate whether this is a useful alternative to metabolic cage restraint for mice, as it was already described for rats [ 39 , 40 ]. To collect more data as part of metabolic phenotyping, the mean arterial pressure and heart rate of mice restrained in different metabolic cage types could be assessed [ 11 ]. Since implantation of a carotid artery catheter is required for this measurement, including anesthesia and surgery before the start of the experiment, we left this quite interesting measurement aside in the sense of the refinement guiding principle.…”

Section: Discussionmentioning

confidence: 99%

“…The energy expenditure of mice may be elevated particularly during metabolic cage housing at 20–22 °C due to the absence of conspecifics and nesting material as mice are deprived of the possibility of keeping themselves warm through huddling and nests [ 9 , 10 ]. The heat of mice is additionally dissipated from the paws via the metal grid [ 11 , 12 ]. To investigate potential cold stress during metabolic cage restraint, thermal images of mice housed in these cage systems may be taken.…”

Section: Introductionmentioning

confidence: 99%

Reduction in Cold Stress in an Innovative Metabolic Cage Housing System Increases Animal Welfare in Laboratory Mice

Wittek,

Touma,

Nitezki

et al. 2023

Animals

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Housing in metabolic cages can induce a pronounced stress response. Metabolic cage systems imply housing mice on metal wire mesh for the collection of urine and feces in addition to monitoring food and water intake. Moreover, mice are single-housed, and no nesting, bedding, or enrichment material is provided, which is often argued to have a not negligible impact on animal welfare due to cold stress. We therefore attempted to reduce stress during metabolic cage housing for mice by comparing an innovative metabolic cage (IMC) with a commercially available metabolic cage from Tecniplast GmbH (TMC) and a control cage. Substantial refinement measures were incorporated into the IMC cage design. In the frame of a multifactorial approach for severity assessment, parameters such as body weight, body composition, food intake, cage and body surface temperature (thermal imaging), mRNA expression of uncoupling protein 1 (Ucp1) in brown adipose tissue (BAT), fur score, and fecal corticosterone metabolites (CMs) were included. Female and male C57BL/6J mice were single-housed for 24 h in either conventional Macrolon cages (control), IMC, or TMC for two sessions. Body weight decreased less in the IMC (females—1st restraint: −6.94%; 2nd restraint: −6.89%; males—1st restraint: −8.08%; 2nd restraint: −5.82%) compared to the TMC (females—1st restraint: −13.2%; 2nd restraint: −15.0%; males—1st restraint: −13.1%; 2nd restraint: −14.9%) and the IMC possessed a higher cage temperature (females—1st restraint: 23.7 °C; 2nd restraint: 23.5 °C; males—1st restraint: 23.3 °C; 2nd restraint: 23.5 °C) compared with the TMC (females—1st restraint: 22.4 °C; 2nd restraint: 22.5 °C; males—1st restraint: 22.6 °C; 2nd restraint: 22.4 °C). The concentration of fecal corticosterone metabolites in the TMC (females—1st restraint: 1376 ng/g dry weight (DW); 2nd restraint: 2098 ng/g DW; males—1st restraint: 1030 ng/g DW; 2nd restraint: 1163 ng/g DW) was higher compared to control cage housing (females—1st restraint: 640 ng/g DW; 2nd restraint: 941 ng/g DW; males—1st restraint: 504 ng/g DW; 2nd restraint: 537 ng/g DW). Our results show the stress potential induced by metabolic cage restraint that is markedly influenced by the lower housing temperature. The IMC represents a first attempt to target cold stress reduction during metabolic cage application thereby producing more animal welfare friendlydata.

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“…Only few studies studied MC housing of mice showing that mice housed in MCs had an increased BP for several hours and prolonged tachycardia las)ng for two days 24 and sugges)ng that MC housing accelerates metabolism 16,[25][26][27] and oxida)ve stress 16 . While some studies showed that mice had stable urina)on rates in the MC aRer 3-4 days 28 , others stated that mice did not acclima)ze 24,25,29 , even aRer three weeks 16 . Acclima)sa)on was paralleled by an increase in food/water intake and urinary output 28,30 .…”

Section: Introduc#onmentioning

confidence: 99%

“…MCs are kept at standard housing condi)ons (ambient temperature of 23°C). However, it remains widely unclear to what extent ambient temperature contributes as a major stressor 16,[24][25][26][27][28][29][30] while a recent study demonstrated a beneficial effect of thermoneutral temperature on some metabolic parameters 27 . To the best of our knowledge, only one study measured body temperatures in mice during MC housing, showing an average body surface temperature of around 30°C at an ambient cage temperature of 22.5°C 25 .…”

Section: Introduc#onmentioning

confidence: 99%

Thermoneutral Environment Improves Mouse Metabolism and Reduces Stress in Metabolic Cages

Seebeck,

Villiger,

Calvet

et al. 2024

Preprint

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Metabolic cages [MCs] are frequently used to collect feces and urine samples. However, MC housing is stressful for mice and thereby potentially influences parameters of interest. We compared a standard protocol for MC housing (4 days at 23°C, including 3 days of permanent acclimatisation and 24h sampling) with a) short-term intermittent acclimatisation (3 days for 3h plus 24h MC housing), b) providing a nest (4 days at 23°C) and c) MC housing at thermoneutrality (4 days at 30°C). C57BL6/N mice were implanted with telemetric transmitters acquiring ECG, blood pressure, body core temperature, and activity. Body core temperature decreased, and heart and respiratory rates increased during MC housing at 23°C. Mice housed in MCs with a nest or at 30°C showed strongly reduced heart/respiratory rates and a higher body core temperature compared to the group housed at 23°C. Mice ate more and lost more weight when housed in MCs at 23°C in combination with a much higher brown fat activity. Torpor-like episodes were observed in male mice housed at 23°C. In addition, they had higher corticosterone levels. Our study demonstrates that MC housing at 23°C strongly influences mouse physiology and metabolism due to a substantial cold stress. Female mice seem to be less affected compared to male mice. MC housing at thermoneutrality offers a simple solution to improve animal wellbeing during MC housing. Moreover, one short-term acclimatization presumably has the same acclimatisation effect as repeated exposure to the MCs.

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Transient hypertension and sustained tachycardia in mice housed individually in metabolism cages

Cited by 24 publications

References 29 publications

Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior

Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior

Reduction in Cold Stress in an Innovative Metabolic Cage Housing System Increases Animal Welfare in Laboratory Mice

Thermoneutral Environment Improves Mouse Metabolism and Reduces Stress in Metabolic Cages

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