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Mitochondrial respiration in rats during hypothermia resulting from central drug administration

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Abstract

The ability to induce a hypothermia resembling that of natural torpor would be greatly beneficial in medical and non-medical fields. At present, two procedures based on central nervous pharmacological manipulation have been shown to be effective in bringing core body temperature well below 30 °C in the rat, a non-hibernator: the first, based on the inhibition of a key relay in the central thermoregulatory pathway, the other, based on the activation of central adenosine A1 receptors. Although the role of mitochondria in the activation and maintenance of torpor has been extensively studied, no data are available for centrally induced hypothermia in non-hibernators. Thus, in the present work the respiration rate of mitochondria in the liver and in the kidney of rats following the aforementioned hypothermia-inducing treatments was studied. Moreover, to have an internal control, the same parameters were assessed in a well-consolidated model, i.e., mice during fasting-induced torpor. Our results show that state 3 respiration rate, which significantly decreased in the liver of mice, was unchanged in rats. An increase of state 4 respiration rate was observed in both species, although it was not statistically significant in rats under central adenosine stimulation. Also, a significant decrease of the respiratory control ratio was detected in both species. Finally, no effects were detected in kidney mitochondria in both species. Overall, in these hypothermic conditions liver mitochondria of rats remained active and apparently ready to be re-activated to produce energy and warm up the cells. These findings can be interpreted as encouraging in view of the finalization of a translational approach to humans.

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Funding

The experiments were funded by the project FARB—Warm up to wake up—from the University of Bologna.

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Author notes

  1. Gianluca Sgarbi and Timna Hitrec contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Biochemistry and Mitochondrial Pathophysiology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Piazza di Porta S. Donato, 2, 40126, Bologna, Italy

    Gianluca Sgarbi, Alessandra Baracca, Francesca Liuzzi & Giancarlo Solaini

  2. Laboratory of Autonomic and Behavioral Physiology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy

    Timna Hitrec, Roberto Amici, Alessia Di Cristoforo, Marco Luppi, Fabio Squarcio, Giovanni Zamboni & Matteo Cerri

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  1. Gianluca Sgarbi
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  2. Timna Hitrec
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  3. Roberto Amici
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Contributions

TH and GSg share first authorship of this publication. Experiment ideation: RA, MC, GZ. Experimental plan design: RA, AB, MC, TH, GSg, GSo, GZ. Surgery: AC, TH. Microinjection in rats: AC, TH, FS. Fasting-induced torpor in mice: AC, TH, FS. Sample collection: MC, TH, ML. Measurement of mitochondrial function: FL, GSg. Mitochondrial data analysis: GSg. Temperature data analysis: TH. Analysis of the results: RA, AB, MC, AC, TH, FL, ML, GSg, GSo, FS, GZ. Interpretation of the findings: RA, AB, MC, TH, GSg, GSo. Manuscript writing: RA, AB, MC, TH, GSg, GSo. Manuscript editing: RA, AB, MC, TH, GSg, GSo, GZ.

Corresponding author

Correspondence to Matteo Cerri.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Communicated by G. Heldmaier.

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Sgarbi, G., Hitrec, T., Amici, R. et al. Mitochondrial respiration in rats during hypothermia resulting from central drug administration. J Comp Physiol B 192, 349–360 (2022). https://doi.org/10.1007/s00360-021-01421-6

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