A critical test of Drosophila anaesthetics: Isoflurane and sevoflurane are benign alternatives to cold and CO2

MacMillan, Heath A.; Nørgård, Mikkel Ø.; MacLean, Heidi J.; Overgaard, Johannes; Williams, Catherine J.

doi:10.1016/j.jinsphys.2017.07.005

Cited by 51 publications

(44 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One limitation of our study was the use of only female flies for behavioral experiments in adults. Sex-specific effects in Drosophila have been observed during recovery from anesthesia, 41,42 although these effects generalize to cold-shock and oxygen deprivation anesthesia, which are likely unrelated to the presynaptic mechanisms described in this study. Given the lack of sexual dimorphism in synaptic proteins, it is unlikely that the phenotypes we describe here would be different using male flies, although this remains to be tested experimentally.…”

Section: Perioperative Medicinementioning

confidence: 56%

Syntaxin1A Neomorphic Mutations Promote Rapid Recovery from Isoflurane Anesthesia in Drosophila melanogaster

et al. 2019

View full text Add to dashboard Cite

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Mutations in the presynaptic protein syntaxin1A modulate general anesthetic effects in vitro and in vivo. Coexpression of a truncated syntaxin1A protein confers resistance to volatile and intravenous anesthetics, suggesting a target mechanism distinct from postsynaptic inhibitory receptor processes. Hypothesizing that recovery from anesthesia may involve a presynaptic component, the authors tested whether syntaxin1A mutations facilitated recovery from isoflurane anesthesia in Drosophila melanogaster. Methods A truncated syntaxin1A construct was expressed in Drosophila neurons. The authors compared effects on isoflurane induction versus recovery in syntaxin1A mutant animals by probing behavioral responses to mechanical stimuli. The authors also measured synaptic responses from the larval neuromuscular junction using sharp intracellular recordings, and performed Western blots to determine whether the truncated syntaxin1A is associated with presynaptic core complexes. Results Drosophila expressing a truncated syntaxin1A (syx227, n = 40) were resistant to isoflurane induction for a behavioral responsiveness endpoint (ED50 0.30 ± 0.01% isoflurane, P < 0.001) compared with control (0.240 ± 0.002% isoflurane, n = 40). Recovery from isoflurane anesthesia was also faster, with syx227-expressing flies showing greater levels of responsiveness earlier in recovery (reaction proportion 0.66 ± 0.48, P < 0.001, n = 68) than controls (0.22 ± 0.42, n = 68 and 0.33 ± 0.48, n = 66). Measuring excitatory junction potentials of larvae coexpressing the truncated syntaxin1A protein showed a greater recovery of synaptic function, compared with controls (17.39 ± 3.19 mV and 10.29 ± 4.88 mV, P = 0.014, n = 8 for both). The resistance-promoting truncated syntaxin1A was not associated with presynaptic core complexes, in the presence or absence of isoflurane anesthesia. Conclusions The same neomorphic syntaxin1A mutation that confers isoflurane resistance in cell culture and nematodes also produces isoflurane resistance in Drosophila. Resistance in Drosophila is, however, most evident at the level of recovery from anesthesia, suggesting that the syntaxin1A target affects anesthesia maintenance and recovery processes rather than induction. The absence of truncated syntaxin1A from the presynaptic complex suggests that the resistance-promoting effect of this molecule occurs before core complex formation.

show abstract

Section: Perioperative Medicinementioning

confidence: 56%

Syntaxin1A Neomorphic Mutations Promote Rapid Recovery from Isoflurane Anesthesia in Drosophila melanogaster

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Emerging adults were transferred to fresh medium vials and 2–4 days post‐eclosion , the flies were anaesthetised briefly (<5 min) with CO 2 to separate the female flies later used for experiments. Female flies were placed in fresh food vials and allowed at least 2 days to recover before they were used for experiments (MacMillan, Nørgård, MacLean, Overgaard, & Williams, ). Accordingly, 4–7 days old flies were used for experiments.…”

Section: Methodsmentioning

confidence: 99%

How to assess Drosophila heat tolerance: Unifying static and dynamic tolerance assays to predict heat distribution limits

2019

Self Cite

View full text Add to dashboard Cite

Thermal tolerance is a critical determinant of ectotherm distribution, which is likely to be influenced by future climate change. To predict such distributional changes, simple and comparable measures of heat tolerance are needed and these measures should ideally correlate with the characteristics of the species current thermal environments. A recent model (thermal tolerance landscapes—TTLs) uses the exponential relation between temperature and knockdown time to describe the thermal tolerance of ectotherms across time/temperature scales. Here, we established TTLs for 11 Drosophila species representing different thermal ecotypes by measuring knockdown time at 9–17 stressful temperatures (0.5°C intervals). These temperatures caused knockdown times ranging from <10 min to >12 hrs and all species displayed the expected exponential relation between temperature and knockdown time (average R2 = 0.98). Previous studies using TTLs have reported a trade‐off between tolerance to acute and chronic heat stress in ectotherms. The present study did not find evidence to support this trade‐off in drosophilids. Instead, we show how this “trade‐off” can arise as an analytical artefact caused by insufficient data collection and excessive data extrapolation. Dynamic assays represent an alternative method to describe heat tolerance of ectotherms, where animals are exposed to gradually increasing temperatures until knockdown. The comparability of static and dynamic assays has previously been questioned, but here we show that static and dynamic assays give comparable information on heat tolerance. Using the constants derived from static TTLs, we mathematically model the expected dynamic knockdown temperature and subsequently confirm this model by comparison to empirically obtained knockdown temperatures from all 11 species. Characterisation of heat tolerance in laboratory settings is an important tool in thermal biology, but more so if the measures correlate with the environmental gradients that characterise the fundamental niche of species. Here, we show that both static and dynamic assays were characterised by strong correlations to precipitation of the driest month and maximum temperature of the warmest month combined (R2 = 0.68–0.71). This demonstrates that both assay types offer simple measures of heat tolerance that are ecologically relevant for the tested drosophilids. A plain language summary is available for this article.

show abstract

“…In another dose–response study on D. melanogaster , exposure times of CO 2 for up to 10 min and 5 min recovery had significant effects on the physiological traits such as locomotor activity and female fecundity, and stress tolerance to temperature, starvation, and desiccation. When 48‐hr recovery time was given, the effects on stress tolerance generally did not persist (Macmillan, Nørgård, Maclean, Overgaard, & Williams, ). These studies strongly suggest the impacts of CO 2 anesthesia on metabolic changes, stress tolerance, behavior, and reproduction.…”

Section: Discussionmentioning

confidence: 99%

CO₂ anesthesia on Drosophila survival in aging research

Shen

Yang

Zhu

et al. 2019

Arch Insect Biochem Physiol

View full text Add to dashboard Cite

Carbon dioxide (CO 2 ) exposure is a common method of anesthesia in studies of Drosophila melanogaster. A number of negative side effects of CO 2 anesthesia have been reported.It is not clear whether the length of CO 2 anesthesia time affects Drosophila survival in aging research. Here, we examined the potential effect of the CO 2 anesthesia time length of 10-150 min. We found that long CO 2 exposure could lead to Drosophila death, more significant in males. The longer the anesthesia time is, the longer it takes for flies to wake up. Long-time CO 2 anesthesia can reduce the lifespan.Our stress tests showed that long-time CO 2 anesthesia can increase the average survival time in both males and females under starvation conditions, but can only increase female lifespan under H 2 O 2 oxidative stress. Long-time CO 2 anesthesia also significantly affects physiological traits, with spontaneous activity increased in females but decreased in males, and reduced female fecundity. Our study suggests that limiting the CO 2 anesthesia time and giving enough recovery time before performing physiological tests are important in Drosophila aging research.

show abstract

A critical test of Drosophila anaesthetics: Isoflurane and sevoflurane are benign alternatives to cold and CO2

Cited by 51 publications

References 45 publications

Syntaxin1A Neomorphic Mutations Promote Rapid Recovery from Isoflurane Anesthesia in Drosophila melanogaster

Syntaxin1A Neomorphic Mutations Promote Rapid Recovery from Isoflurane Anesthesia in Drosophila melanogaster

How to assess Drosophila heat tolerance: Unifying static and dynamic tolerance assays to predict heat distribution limits

CO₂ anesthesia on Drosophila survival in aging research

Contact Info

Product

Resources

About

A critical test of Drosophila anaesthetics: Isoflurane and sevoflurane are benign alternatives to cold and CO2

Cited by 51 publications

References 45 publications

Syntaxin1A Neomorphic Mutations Promote Rapid Recovery from Isoflurane Anesthesia in Drosophila melanogaster

Syntaxin1A Neomorphic Mutations Promote Rapid Recovery from Isoflurane Anesthesia in Drosophila melanogaster

How to assess Drosophila heat tolerance: Unifying static and dynamic tolerance assays to predict heat distribution limits

CO2 anesthesia on Drosophila survival in aging research

Contact Info

Product

Resources

About

CO₂ anesthesia on Drosophila survival in aging research