0068 Exogenous Heat Shock Protein 70 kDa Facilitates the Restoration of Sleep and Thermoregulatory Characteristics in Rat Endotoxemia Model

Endotoxemia is characterized by the sleep impairment and marked changes in thermoregulation and other physiological functions. The heat shock proteins 70 kDa (Hsp70) were shown to possess protective effects against numerous stress factors, including endotoxemia, in both in vitro and in vivo experiments. The purpose of the present study was to examine the effects of exogenous Hsp70/Hsc70 on sleep and thermoregulatory characteristics in rat endotoxemia model. Male Wistar rats were implanted with electrodes for polysomnography and thermistor to measure brain temperature. The endotoxemia model was established by the intravenous injection of lipopolysaccharide (LPS). Exogenous Hsp70/Hsc70 (purified and consisting of constitutive and inducible isoforms) was injected 15 min before LPS. In control experiments, animals received the intravenous injections of vehicle (saline). Recordings were performed for 24 hours using the SASR 8800 system. The injections of LPS evoked the increase in total time of slow-wave sleep (SWS) within 2-5 hours (due to the increase in number of its episodes) and the decrease in total time of wakefulness and rapid-eye-movement sleep (REM). The rise in brain temperature and contractile muscular activity (CMA) were observed within 2-7 and 1-5 hours respectively. The pre-treatment of animals by Hsp70/Hsc70 caused the restoration of total time of SWS and wakefulness an hour earlier and the recovery of total time of REM 2 hours earlier in comparison with LPS alone. Although the total amount of SWS remained high, its structure was changed due to the increase in episode duration and SWS become less fragmented. Furthermore, Hsp70/Hsc70 injection led to the attenuation of febrile rise in brain temperature and CMA and to restoration of these parameters 3 and 2 hours earlier, respectively. The pre-treatment by Hsp70/Hsc70 can hasten the restoration of temporal characteristics of sleep and wakefulness, evoke the elongation of SWS episodes and reduce the rise in brain temperature and CMA during endotoxemia. Thus Hsp70 may provide the protective effect during endotoxemia and possess anti-inflammatory therapeutic potential. Government contract (topic № AAAA-A18-118012290427-7)