Neurophysiological and metabolic regulation of spontaneous and synthetic torpor: a translational perspective

Torpor is an energy-saving physiological state characterized by a transient and reversible decrease in metabolic rate and core temperature, which occurs in different species in conditions of scarce food availability. At present, the mechanism underlying torpor occurrence is unknown. The attempt to imitate natural torpor is pursued in clinical practice, in order to overcome the severe side effects that follow the induction of therapeutic hypothermia. Several attempts to induce a torpor-like state (synthetic torpor) by manipulating central nervous activity have been made in rodents. Most promising are the activation of central adenosine type-1 receptors and the pharmacological inhibition of the Raphe Pallidus (RPa). Aims of the present project were: i) to unravel the neural pathway of spontaneous torpor in mice, a species that enters daily torpor spontaneously; ii) to understand the possible mechanism of metabolic rate reduction in spontaneous and synthetic torpor, in mice and rats, respectively, by evaluating mitochondrial activity during deep hypothermia; iii) to explore the possibility to induce synthetic torpor in a large mammal, the swine, by the central manipulation of the RPa. In summary, the results showed that: i) Paraventricular and Dorsomedial Hypothalamic nuclei showed a specific neural activation at the entrance in torpor; ii) liver mitochondria showed a reduction in maximum respiration rate in spontaneous, but not in synthetic torpor, while no major changes occurred in kidney and brain; iii) central manipulation of the RPa in swine induced physiological modifications similar to those observed in rats.