Central and peripheral manipulation of the sympathetic nervous system to study immune, thermoregulatory and sleep-related neural functions

The primary aim of this thesis has been to investigate the effects of central and peripheral Sympathetic Nervous System manipulation on immune responses and on hypothermia and sleep-related brain neural plasticity, through three different sub-projects. The first sub-project investigated the role of the endogenous inflammatory reflex in mice: it is activated in response to immune challenges and its efferent pathway, the splanchnic anti-inflammatory pathway (SAIP), inhibits the inflammatory response to immune challenges. The effects of prior bilateral section of the greater sympathetic splanchnic nerves on cytokine responses to three different systemic immune challenges were investigated: LPS, TLR4 agonist; Poly I:C, TLR3 agonist; and Pam2cys, TLR2 and TLR6 agonist. The results showed that each challenge active the SAIP in mice, resulting in the enhance of systemic levels of the anti-inflammatory cytokines and the inhibition of those of pro-inflammatory cytokines. The second sub-project investigated the effects of synthetic torpor (ST) and of the following recovery period on cortical and hippocampal Tau protein (τp) expression. Animals entering both natural and ST accumulate the hyperphosphorylated τp, resembling a similar pattern observed in tauopathies. However, this accumulation is reverted when animals recover from torpor. In this study, the levels of the τp, its phosphorylation/dephosphorylation processes, and the plasma levels of some hormones and transmitters were determined in rats subjected to and recovering from ST. The results confirmed the reversibility of the τp phosphorylation after the arousal from ST. Moreover, during ST and its recovery, plasma melatonin concentration increased. The third sub-project investigated the role of sleep, through a sleep deprivation protocol, in the levels of the τp and its phosphorylation/dephosphorylation processes, 3 and 6 hours after the exit from ST. The results showed that sleep deprivation did not impair τp dephosphorylation process, but apparently accelerated it through a finely regulated process, without affecting melatonin levels.