[Endogenous anticonvulsants: neuropeptide Y and delta sleep inducing peptide].

INTRODUCTION: The same neuropeptides regulate both cicle sleep-wake and excitability of the brain. CONCLUSION: Literature data together with our results support the idea that delta sleep--inducing peptide and neuropeptide Y could represent one of the factors of the endogenous stabilization of brain excitability and potent antiepileptic in generalized metaphit-induced audiogenic convulsive activity. The same holds true for DSIP analogues.

[Sleep and anesthesia--Part 1, Recent findings in research].

We described how modern neuroscience has elucidated what is sleep and its implication, and also reviewed histological and current trends in search of sleep mechanism from view of neurocirculatory or hormonary basis studies. We conclude that anesthesia and sleep share some neuronal structure in their action and mechanism of anesthesia could be elucidated through sleep study. In addition, anesthesia-related sleep disturbance must be settled to serve satisfied quality of life of patients and to save economic and medical resources.

Delta sleep-inducing peptide (DSIP): a still unresolved riddle.

Delta sleep-inducing peptide (DSIP) was isolated from rabbit cerebral venous blood by Schoenenberger-Monnier group from Basel in 1977 and initially regarded as a candidate sleep-promoting factor. However, the link between DSIP and sleep has never been further characterized, in part because of the lack of isolation of the DSIP gene, protein and possible related receptor. Thus the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak. Although DSIP itself presented a focus of study for a number of researchers, its natural occurrence and biological activity still remains obscure. DSIP structure is different from any other known representative of the various peptide families. In this mini-review we hypothesize the existence of a DSIP-like peptide(s) that is responsible (at least partly) for DSIP-like immunoreactivity and DSIP biological activity. This assumption is based on: (i) a highly specific distribution of DSIP-like immunoreactivity in the neurosecretory hypothalamic nuclei of various vertebrate species that are not particularly relevant for sleep regulation, as revealed by the histochemical studies of the Geneva group (Charnay et al.); (ii) a large spectrum of DSIP biological activity revealed by biochemical and physiological studies in vitro; (iii) significant slow-wave sleep (SWS) promoting activity of certain artificial DSIP structural analogues (but not DSIP itself!) in rabbits and rats revealed by our early studies; and (iv) significant SWS-promoting activity of a naturally occurring dermorphin-decapeptide that is structurally similar to DSIP (in five of the nine positions) and the sleep-suppressing effect of its optical isomer, as revealed in rabbits. Potential future studies are outlined, including natural synthesis and release of this DSIP-like peptide and its role in neuroendocrine regulation.

A quartet neural system model orchestrating sleep and wakefulness mechanisms.

Physiological knowledge of the neural mechanisms regulating sleep and wakefulness has been advanced by the recent findings concerning sleep/wakefulness-related preoptic/anterior hypothalamic and perifornical (orexin-containing)/posterior hypothalamic neurons. In this paper, we propose a mathematical model of the mechanisms orchestrating a quartet neural system of sleep and wakefulness composed of the following: 1) sleep-active preoptic/anterior hypothalamic neurons (N-R group); 2) wake-active hypothalamic and brain stem neurons exhibiting the highest rate of discharge during wakefulness and the lowest rate of discharge during paradoxical or rapid eye movement (REM) sleep (WA group); 3) brain stem neurons exhibiting the highest rate of discharge during REM sleep (REM group); and 4) basal forebrain, hypothalamic, and brain stem neurons exhibiting a higher rate of discharge during both wakefulness and REM sleep than during nonrapid eye movement (NREM) sleep (W-R group). The WA neurons have mutual inhibitory couplings with the REM and N-R neurons. The W-R neurons have mutual excitatory couplings with the WA and REM neurons. The REM neurons receive unidirectional inhibition from the N-R neurons. In addition, the N-R neurons are activated by two types of sleep-promoting substances (SPS), which play different roles in the homeostatic regulation of sleep and wakefulness. The model well reproduces the actual sleep and wakefulness patterns of rats in addition to the sleep-related neuronal activities across state transitions. In addition, human sleep-wakefulness rhythms can be simulated by manipulating only a few model parameters: inhibitions from the N-R neurons to the REM and WA neurons are enhanced, and circadian regulation of the N-R and WA neurons is exaggerated. Our model could provide a novel framework for the quantitative understanding of the mechanisms regulating sleep and wakefulness.

[Individuality of emotional stress].

The author postulates a need of individual evaluation of experimental data characterizing emotional stress. In typical conflict situations inducing emotional stress, there are animals resistant or predisposed to disturbance of different physiological functions. Prognostic criteria of individual resistance of animals to stressors are presented. Stress resistance depends in large on neuromediators and neuropeptides content, in particular Substance P, a peptide responsible for delta-sleep, and beta-endorphin, in brain structures and peripheral tissues. It is emphasized that individual estimation of clinical indices of emotional stress is needed.

Structural-functional organization of neurons in the cerebral cortex of rats with different levels of resistance to emotional stress in conditions of exposure to delta sleep-inducing peptide.

Wistar rats with different levels of resistance to emotional stress (ES) were subjected to stress and brain sections stained with Nissl cresyl violet were used for quantitative analysis of the structural organization of neurons in layer V of the sensorimotor cortex. Some animals received delta sleep-inducing peptide (DSIP) 1 h before stress. Control ES-susceptible rats, as compared with resistant rats, had lower levels of normochromic and moderately hypochromic neurons. Normochromic neurons were not seen after stress. Rats susceptible to ES showed particularly sharp decreases in moderately hypo- and hyperchromic neurons, along with increases in the proportions of extremely hypo- and hyperchromic neurons, ghost cells, and ischemically altered cells. After administration of DSIP before stress, ischemically altered cells were not seen in any group: the level of reduction of extremely hyperchromic neurons was smaller in ES-susceptible rats than in ES-resistant rats. It is suggested that brain hypoxia plays a particular role in disorganizing the cortex in conditions of ES, while DSIP has both antistress and antihypoxic properties.

Dizocilpine blocks the effects of delta sleep-inducing peptide-induced suppression of c-fos gene expression in the paraventricular nucleus of the hypothalamus in rats.

The characteristics of the actions of the non-competitive blocker of NMDA receptors dizocilpine on the expression of the early c-fos gene in the paraventricular nuclei of the hypothalamus were studied in rats with different predicted susceptibilities to emotional stress in conditions of treatment with delta sleep-inducing peptide. The results showed that prior treatment with dizocilpine blocked reductions in c-fos expression induced by delta sleep peptide.

[Dizocilpine inhibits suppression of c-fos gene by delta-sleep peptide in the rat hypothalamic paraventricular nucleus]. / Dizotsilpin blokiruet éffekty podavlenia peptidom del'ta-sna ékspressii gena c-fos v paraventrikuliarnom iadre gipotalamusa u krys.

The effects of intracerebroventricular administration of the non-competitive NMDA-receptor blocker Dizocilpine (MK-801) on delta sleep-inducing peptide (DSIP) suppression of c-fos induction, were studied. The data obtained indicate that preliminary i.c.v. MK-801 injection inhibits immediate early gene c-fos suppression by DSIP in the parvocellular paraventricular hypothalamus.

[Features of regulating delta sleep-inducing peptide by free radical processes in tissue and erythrocyte membranes in intact animals and under stress]. / Osobennosti reguliatsii del'ta-son indutsiruiushchim peptidom svobodnoradikal'nykh protesessov v tkaniakh i membranakh éritrotsitov intaktnykh zhivotnykh i pri stresse.

In activity the comparative analysis of metabolic effects delta--sleep inducing peptide (DSIP) in tissues and erythrocytes of intact rats and under cold stress is conducted. The regulation effect of DSIP in attitude of free radical processes will be realised through modulation the prooxidant--antioxidant balance: both for intact animal, and at stress. Exogenous DSIP increases the antioxidant system activity in tissues of brain, liver and blood in standard conditions and under cold stress. The anti-stress effect of DSIP is directed as on increase of power endogenic enzymatic antioxidant system activity, specially glutathione peroxidase activity, and not enzymatic of antioxidant protection. The DSIP renders different influence on activity of prooxidant enzymes: for intact animal boosts the myeloperoxidase activity in blood neutrophils, not rendering essential influencing on the xanthine oxidase activity in tissues of brain, liver and activates the myeloperoxidase activity, depresses the xanthine oxidase activity for rats at stress. The membranotropic effect of DSIP in the norm and under stress is connected to increase of stability of protein--lipid interplays. The membranostabilizing effect of DSIP in conditions of stress is characterized decrease of polarity of lipid phase and negative surface charge of erythrocyte membranes, modified in course of lipid peroxidation.

[c-fos Gene expression during emotional stress in rats: blocking by delta sleep-inducing peptide]. / Ekspressiia gena c-fos pri émotsional'nom stresse u krys: blokiruiushchaia rol' peptida, vyzyvaiushchego del'ta-son.

An emotional stress induces an obvious immediate early gene c-fos expression in the brain limbic structures in the rats predisposed to emotional stress. Administration of the delta-sleep-inducing peptide (DSIP) was shown to inhibit the c-fos expression. It led to an obvious inhibition of the c-fos expression in paraventricular nuclei of the hypothalamus, medial and lateral parts of the septum of rats predisposed to emotional stress. This mechanism seems to play an important role in the DSIP anti-stress effects.

Regulation by delta-sleep-inducing peptide of the neurochemical changes in the brain associated with dopaminergic system hyperactivity.

The influence of a single injection of "delta-sleep-inducing peptide" (DSIP; 30 microg/kg body weight) on neurochemical parameters of rats' brain was studied under the conditions of chronic administration of dopamine analogs inducing DA-system hyperactivity - 50 mg/kg body weight of L-DOPA for 30 days or 2,5 mg/kg body weight of amphetamine for 21 days. The parameters of serotonergic system (MAO A activity, 5-HT, and 5-HIAA contents) and of dopaminergic system (MAO B activity, DA, NA, and HVA contents) were investigated in the cortex and caudate nucleus of control, DA or amphetamine, and DSIP receiving rats. Changes caused by the two DA-system activating drugs had both similarities and differences, and the corrective action of DSIP also had certain peculiarities depending on the pharmacological preparation used for the induction of DA-system hyperactivity and on the investigated brain structure. It is supposed that DSIP action might be based on the activation of serotonergic system that ensures the adaptive behavior of the animals.

[The role of the delta sleep-inducing peptide in the formation of neuropathological syndromes]. / Rol' del'ta-son-indutsiruiushchego peptida v formirovanii neiropatologicheskikh sindromov.

The authors considered the pathogenetic role of delta-sleep inducing peptide (DSIP) in different neuropathological syndromes development and manifestation. According to own as well as published in the literature data authors showed the parkinsonian and the rotational syndromes development following DSIP central administration. Briefly, DSIP is a neuropeptide which play significant role in the mechanisms of development of different neuropathological syndromes, namely, epileptic, parkinsonian, withdrawal, rotational and others syndromes.

[A neurophysiological analysis of the mechanisms of neuroendocrine regulation in stress and under the antistress action of the delta sleep-inducing peptide]. / Neirofiziologicheskii analiz mekhanizmov neiroéndokrinnoi reguliatsii pri stresse i antistressovom deistvii peptida del'ta-sna.

In the article one can find analysis of modern theories about mechanisms of neuroendocrine regulation under stress, influence of steroid hormones and neuropeptides (delta-sleep-inducing peptide) on the functional state of hypothalamic reticular limbic structures of the brain. Special attention is paid to the analysis of mechanisms of creation of integrative processes under aggressive-defensive behaviour and roles of biologically active factors in the regulation of the processes.

[The physiological properties of endogenous oligopeptides that enhance resistance to emotional stress]. / Fiziologicheskie svoistva éndogennykh oligopeptidov, povyshaiushchikh ustoichivost' k émotsional'nomu stressu.

In the work was studied the effect of the delta-sleep inducing peptide (DSIP) on the substance P (SP) content in the hypothalamus of August rats genetically predisposed to emotional stress. The hypothalamic SP level increased 3 h and 6 h after systemic i. p. DSIP administration in doses of 60 and 120 nM/kg. The effects of i. p. DSIP administration on the hypothalamic SP were studied on an experimental model of aggressive-conflict behaviour in rats. The peptide was injected before the animals were exposed to stress. Quintuple DSIP administration in the above mentioned doses before exposing rats to stress induced highly significant increase in the hypothalamic SP. Single DSIP injections also significantly elevated SP values, reduced the adrenal hypertrophy and the thymus involution resulting in an increase of the rats' survival as compared to the control animals exposed to stress without DSIP. The antistressor effect of DSIP is assumed to be realized through the increase of the hypothalamic SP which is a factor enhancing the animal resistance to emotional stress.

[The current concepts of the mechanisms of the interaction of the CNS and the hypophyseal-adrenal system under the ordinary conditions of the activities of living]. / Sovremennye predstavleniia o mekhanizmakh vzaimodeistviia TsNS i gipofizarno-nadpochechnikovoi sistemy v obychnykh usloviiakh zhiznedeiatel'nosti.

Elucidation of mechanisms of hormonal influence on the CNS function is one of the primary concerns of neuroendocrinology. The study of the action of hormones on nervous centres is hampered by extraordinary complexity of morphological and functional organization of the CNS. Inquiry into the influence of hormones on separate structures of the hypothalamo-reticulo-limbic complex regulating emotional state and motivated behavior, allows to approach the task. Consideration is given to the present knowledge about effects of adrenal cortex steroids and peptides (delta-sleep, etc.) on functional state of various brain structures and their role in integrative processes in the central nervous system. Special attention is attributed to discussions of current understanding of the CNS-hypophysial/adrenal interactions in normal environments, and to formation of inter-central interactions with assistance of hormones and neuropeptides.