Neurophysiological, molecular and pathophysiological aspects of synthetic torpor

Synthetic torpor is a peculiar physiological condition resembling natural torpor, in which even non-hibernating species can be induced through different pharmacological approaches. The growing interest in the induction of a safe synthetic torpor state in non-hibernating species stems from the possible applications that it may have in a translational perspective. In particular, the deeper understanding of the functional changes occurring during and after synthetic torpor may lead to the standardization of a safe procedure to be used also in humans and to the implementation of new therapeutic strategies. Some of the most interesting and peculiar characteristics of torpor that should be assessed in synthetic torpor and may have a translational relevance are: the reversible hyperphosphorylation of neuronal Tau protein, the strong and extended neural plasticity, which may be related to Tau regulatory processes, and the development of radioresistance. In this respect, in the present thesis, rats were induced into synthetic torpor by the pharmacological inhibition of the raphe pallidus, a key brainstem thermoregulatory area, in order to assess: i) whether a reversible hyperphosphorylation of Tau protein occurs at the spinal cord level, also testing the possible involvement of microglia activation in this phenomenon; ii) sleep quality after synthetic torpor and its possible involvement in the process of Tau dephosphorylation; iii) whether synthetic torpor has radioprotective properties, by assessing histopathological and molecular features in animals exposed to X-rays irradiation. The results showed that: i) a reversible hyper-phosphorylation of Tau protein also occurs in synthetic torpor in the dorsal horns of the spinal cord; ii) sleep regulation after synthetic torpor seems to be physiological, and sleep deprivation speeds up Tau dephosphorylation; iii) synthetic torpor induces a consistent increase in radioresistance, as shown by analyses at both histological and molecular level.