Cardioprotective Effect of Modified Peroxiredoxins in Retrograde Perfusion of Isolated Rat Heart under Conditions of Oxidative Stress.

Antioxidant properties of recombinant peroxiredoxin-6 and chimeric protein PSH combining peroxidase and superoxide dismutase activities were studied on the model of retrograde perfusion of isolated rat heart under conditions of H2O2-induced oxidative stress. The exogenous antioxidant proteins exhibited cardioprotective properties manifested in heart rate normalization, maintenance of contractile activity of the myocardium, and prevention of H2O2-induced LPO in oxidative stress. Localization of peroxiredoxin-6 and PSH in the cardiac tissue was determined and myocardial structures most effectively protected by the antioxidant enzymes from ischemia/reperfusion-induced damages were identified. The results suggest that modified peroxiredoxins are promising components of perfusion media for preservation of isolated organs.

Neuropeptide modulation of evoked responses of neurons in the medial septal region of hibernating ground squirrels in conditions of chronic isolation of the medial septal region from preoptic-hypothalamic structures.

Septal slices from hibernating ground squirrels were initially (for two weeks) subjected to basal separation of the septal region and were then used for studies of the effects of neuropeptides extracted from the brains of hibernating animals (TSKYR, TSKY, and DY) and monoaminergic neurotransmitters (noradrenaline and serotonin) on neuronal responses evoked by intraseptal electrical stimulation. Despite removal of a large complex of afferent connections and direct contacts with the preoptic region, the neurons retained their normal reactivity and the normal distribution of response types. Neuropeptides efficiently modulated responses, and had strong facilitatory effects on oligosynaptic short-latency responses consisting of single spikes. In most cases (78% of tests), effects on evoked activity were independent of effects on baseline discharge frequency. These data lead to the suggestion that neuropeptides have two influences on septal neurons: a direct, non-synaptic influence on the pacemaker potential responsible for baseline activity, and modulation of synaptic processes. Analysis showed that retention of descending septohippocampal connections was not critical for entry into hibernation and the tonic maintenance of this state. The effects of preoptic-hypothalamic mechanisms of hibernation determine the paradoxical latent excitability of septal cells, allowing the septohippocampal system to filter external signals and provide for urgent arousal of the forebrain during hibernation.

The paradoxically high reactivity of septal neurons in hibernating ground squirrels to endogenous neuropeptides is lost after chronic deafferentation of the septum from the preopticohypothalamic areas.

The effect of neuropeptides (TSKYR, TSKY and DY) and neurotransmitters (serotonin and noradrenaline) on the activity of medial septum (MS) neurons from the brain of summer wakening ground squirrels (WGS), hibernating ground squirrels (HGS), and hibernating ground squirrels with the undercut septum (UHGS) was studied. It was shown that in HGS, the neuropeptides were substantially more effective in modulating the spontaneous activity of MS neurons than in WGS. The undercutting of MS led to the disappearance of the increased responsiveness to the neuropeptides: in UHGS, neuropeptide-induced changes in the spontaneous activity became nearly identical to those in WGS. The decrease in MS responsiveness in UHGS is due mainly to pacemaker neurons, which cease to respond to the peptides. It was shown that the neuropeptides have a dual effect: they change the level of spontaneous activity through direct modulation of pacemaker potential and control responses to electrical stimulation by modulating the synaptic transmission. Contrary to neuropeptides, neurotransmitters were highly effective in neurons of all groups of animals. Presumably, the enhanced excitability of MS during hibernation, which is necessary for performing the 'sentry post' function, is formed under the influence of the preopticohypothalamic area, and this influence is mediated by peptides.