SOMNOGENIC EFFECTS OF HEAT-SHOCK PROTEIN 70 DURING PERIOD AFTER STRESS CAUSED BY SLEEP DEPRIVATION

Ekimova I.V., Lapshina K.V., Pastukhov Iu.F., Khudik R.A., Andreeva L.I., Magulis B.A.
Sechenov Institute of Evolutionary Physiology and Biochemistry
Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia

An enhanced expression of heat-shock protein (HSP), including HSP70, in the hypothalamus and other brain structures during sleep deprivation is considered as a neuroprotective response to prolonged wakefulness [Terao et al., 2003]. It is unclear whether the major stress protein HSP70 is involved in the recovery of sleep after its deprivation. In the present study pigeons were totally deprived of sleep by tactile stimulation for 5 h (4 h before and 1 h after the onset of the dark phase). After cessation of the deprivation HSP70 (isolated from a bovine muscle) was applied to the III ventricle in a dose 1.5 g/0.5 l as (a) pyrogenically active (HSP70pyr) [Pastukhov et al., 2003] and (b) put through polymyxin B-containing columns to liberate it from the endotoxin lipopolysaccharide (HSP70lib). EEG, EOG, EMG, ECG, brain (Tbr) and foot skin temperature were recorded and analysed for 12-24 h with 1 s space using a computer system [Rashotte et al., 1998]. In control conditions, HSP70pyr increased Tbr (by 0.3-0.4 C for 3-4 h) and lengthened nonREM sleep (NS) on the average, by 20% for 4-6 h). Application of HSP70lib was accompanied by a prolonged decrease in Tbr and a shorter increase in NS, as compared with HSP70pyr. In the course of sleep deprivation Tbr rose by 0.3-0.5 C, in the 1st h after its cessation wakefulness prevailed, and a rebound effect of NS (a 15% increase) was observed only in the 2nd h. Injection of HSP70pyr after termination of the deprivation led not to an increase, as in control, but to a decrease in Tbr (0.3-0.4 С till the end of the darkness), in the 1st h wakefulness still prevailed, and NS gradually increased from 2nd h to the 9th h after the injection. HSP70lib caused a more appreciable fall in Tbr and a longer NS immediately after cessation of the deprivation. It was shown that increased NS postsleep deprivation is associated with decreased cortisol level [Vgontzas et al., 1999]. We hypothesized that an increase in NS is a functional marker of the stress-limiting effect of HSP70. The study was suppoted by RFRF (grant 03-03-33024) and RAS Presidium ("Basic sciences to medicine" Program).