Delta sleep-inducing peptide and Deltaran: potential approaches to antistress protection.

The aims of the present work were to perform a comparative study of the effects of delta sleep-inducing peptide and Deltaran on neurons in emotiogenic brain structures and to address the question of whether it is possible to prevent or decrease the negative influences of stress loads on the severity of subsequent cerebral ischemia in rats, using glycine with delta sleep-inducing peptide combined in the neuroprotective formulation Deltaran. The results showed that Deltaran and delta sleep-inducing peptide had largely the same actions on the nature of spike activity of neurons in the dorsal hippocampus, paraventricular nucleus of the hypothalamus, and ventral anterior nuclei of the thalamus, evoking activation of some of the neurons in these brain structures. The dorsal hippocampus was dominated by activation of spike activity in response to administration of delta sleep-inducing peptide; Deltaran produced activation mainly in the paraventricular nuclei of the hypothalamus. In all animals given Deltaran, the index of brain blood supply was significantly greater than in animals not given Deltaran. The survival rate of cerebral ischemia was 100% in animals given Deltaran. Death occurred in 38% of animals not given Deltaran.

[The delta sleep-inducing peptide, its analogs and the serotoninergic system in the development of anticonvulsant action]. / Del'ta-son indutsiruiushchii peptid, ego analogi i serotoninergicheskaia sistema v razvitii protivosudorozhnogo deistviia.

A seizure-protecting effect of the delta-sleep-inducing peptide (DSIP) and its analogues was revealed. An intensive sorption of H3 tryptophan occurred under the effect of the DSIP and its analogues. The data obtained suggests that the serotoninergic system plays no important part in the seizure-protecting effect.

[The effect of the intranigral use of the delta sleep-inducing peptide and its analogs on the motor and seizure activities of rats]. / Vliianie vnutrinigral'nogo primeneniia del'ta-son indutsiruiushchego peptida i ego analogov na dvigatel'nuiu i sudorozhnuiu aktivnost' krys.

The effects of delta-sleep inducing peptide (DSIP) and its analogues (1-4) administered into substantia nigra pars reticulata on locomotor and seizure activity were estimated in experiments in rats. It was shown that intranigral microinjection of DSIP as well as DSIP-1-DSIP-4 caused decreasing of horizontal, vertical locomotor activity and attendance of central sectors of the "open field". Antiseizure effects, i.e. the first and clonic-tonic picrotoxin-induced convulsive latent period lengthening and their intensity decreasing, revealed DSIP, DSIP-2 and DSIP-3. Authors suppose that changes of DSIP structure lead to changes of effects expression on locomotor and seizure activity in conditions of their administration into substantia nigra reticulata. Obtained data concerning protective effects of studied peptides on experimental seizure syndrome allow to conclude that there is interaction between DSIP-induced hypokinesia and DSIP analogues anticonvulsive effectiveness in case of their intranigral administration which is likelihood is one of the component of nigral-dependent seizure-suppressive mechanism.

[Changes in the intensity of free-radical reactions in the organs of rats under hypokinetic stress and with protection by the delta sleep-inducing peptide and its tyrosine-containing analog]. / Izmeneniia intensivnosti svobodnoradikal'nykh reaktsii v organakh krys pri gipokineticheskom stresse i zashchite del'ta-son-indutsiruiushchim peptidom i ego tirozinsoderzhashchim analogom.

Dynamics of the hypokinesia-induced changes of free radical and malonic dialdehyde content in brain, the changes of respiratory chain state and superoxide dismutase activity in liver of rats has been studied using ESR technique and biochemical methods. The effect of the preliminary injection of DSIP and its analogue ID-2 on these dynamics has also been studied. Using a model system constants of the interaction between DSIP or ID-2 and O2-. have been determined. The data point to the antioxidant effect of the administration of the peptides before hypokinesia. This suggests that the effect involves in mechanisms of the anti-stress action of these peptides.

[The frequency composition of the brain electrical activity in rats after the use of the delta-sleep peptide and its analogs]. / Chastotnyi sostav élektricheskoi aktivnosti mozga krys posle primeneniia peptida del'ya-sna i ego analogov.

Frequency spectra of brain electrograms in the course of 1 h after peripheral and central administration of the delta-sleep peptide (DSIP) or two its analogues were studied in freely moving rats. In autumn series of experiments carried out on 18 animals was revealed the phase action of DSIP being manifested in initial (up to 20 min after the injection) suppression of fast (20-26 Hz) oscillations in electrocorticograms and their augmentation in subsequent intervals. Under the identical conditions analogues of DSIP induced the effects characteristic for different phases of DSIP action. In spring-summer series of experiments carried out in 6 animals was revealed a significant increase of the delta-waves in electrical activity of the Putamen after intraperitoneal injection of DSIP and its first analogue. Under the conditions of intraventricular injection DSIP induced stable augmentation of oscillations in a diapason of 14-16 Hz in the neocortex, and its analogues induced similar changes in a nearby frequency diapason of 9.6-11 Hz.

[The effect of the delta sleep-inducing peptide on seizure activity]. / Vliianie del'ta-son-indutsiruiushchego peptida na sudorozhnuiu aktivnost'.

The delta-sleep-inducing peptide (DSIP) suppressed seizure activity in the cat cortical strychnine-induced seizure foci. The DSIP delayed development of corazol kindling in rats, prevented seizure induced with bicucullin and other agents in mice. The DSIP effect was shown to be realised through the action upon reticular black substance. The DSIP seems to take part in endogenous control of the brain excitability.

[Antimetastatic effect of the delta-sleep peptide during stress in mice with Lewis' lung carcinoma]. / Antimetastaticheskii éffekt peptida del'ta-sna pri stresse u myshei s kartsinomoi legkogo L'iuis.

The experiments on C57Bl mice with metastatic Lewis lung carcinoma have shown that peptide delta-sleep (DSIP) lowers the stimulation of metastatic spreading which is observed in combination of the surgical removal of the tumour with the emotional-painful stress. The antimetastatic effect is accompanied by stabilization of neurohumoral indices, by a decrease in the intensity of lipid peroxidation and of the acid cathepsin activity in the blood vessels and in the lung tissue.

[Electroencephalographic analysis of inter-central relations in hypothalamo-reticulo-limbic brain structures during treatment with corticosteroids and neuropeptides]. / Elektroéntsefalograficheskii analiz mezhtsentral'nykh vzaimootnoshenii gipotalamoretikulolimbicheskikh struktur mozga pri deistvii kortikosteroidov i neiropeptidov.

Intercentral relations between hypothalamus, limbic system and reticular formation were studied in rabbits and rats under systemic and central action of DSIP, ACTH, corticosteroids and stress (aggressive-defensive behaviour). The results obtained demonstrate changes in the adrenal cortex resulting from stress-inducing adrenocortical hormone content. The increase was achieved by the rise in ACTH level resulting in corticosteroid level elevation (endogenous elevation-aggressive behaviour) and by corticosteroid injections (exogenous elevation). Correlation analysis of structural interrelations after ACTH and corticosteroid injections demonstrated an increased correlation between hypothalamo-reticular-limbic structures. DSIP was shown to have an opposite effect. Correlation analysis revealed the potentials for the formation of new functional interrelations between hypothalamo-reticular-limbic structure in the motivation of aggression (stress) and the levels of corticosterone and DSIP. DSIP action depends on the initial corticosteroid blood level and is more marked in stress-inducing concentrations.

[Protective effect of the neuropeptide homocarnosine in hyperbaric oxygenation]. / Protektornoe deistvie neiropeptida gomokarnozina pri giperbarooksigenatsii.

Homocarnosine, at a dose of 10 mg per 100 g of animal body mass administered intraperitoneally within 15 min before hyperbaric oxygenation with 0.7 MPa of oxygen, exhibited a protective effect. After administration of the neuropeptide into animals before hyperbaric oxygenation a latent period of oxygen convulsions was increased; content of homocarnosine and gamma-aminobutyric acid (GABA) was maintained at the level found in brain of control animals. In brain tissue of unprotected animals content of homocarnosine and GABA was decreased due to the oxygen treatment. GABA was less effective, its protective dose exceeded 10-fold the dose of homocarnosine. The neuropeptide exhibited antioxidant properties in reactions of lipid peroxidation under normal conditions and in hyperbaric oxygenation in vitro. The antioxidant activity of GABA was distinctly lower as compared with homocarnosine.