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The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

The effects of chronic intranasal administration of 300 nmol/kg obestatin and its fragment FNAP-NH2 on behavioral activity and nociceptive threshold were examined in male Wistar rats with normal body weight or alimentary obesity. In normal rats, obestatin produced no effect on behavior and nociception, whereas FNAP-NH2 fragment enhanced risk-taking behavior. Rats with excess body weight demonstrated less pronounced risk-taking behavior and elevated nociceptive threshold in comparison with normal animals, but these differences were abolished by chronic administration of FNAP-NH2.

We report here the first studies of the effects of acute hypobaric hypoxia (AHH)during the period of early organogenesis on three sequential generations: the generation including pregnant females exposed to AHH (F0) and the two subsequent generations – F1 and F2. All three generations showed significant abnormalities in behavioral measures of motor and orientational-investigative activity, reflecting the state of anxiety, while generations F1 and F2 also showed changes in the ability of offspring to learn with positive reinforcement. These changes persisted to the pubertal period of life. In addition, females of generations F0 and F1 showed influences of AHH on maternal behavior, these influences being in different directions. The possible mechanisms of the effects of gestational stress during early organogenesis on subsequent generations are discussed.

We studied the effects of the anorexigenic peptide obestatin on the coagulation system and blood rheology (by the parameters of platelet aggregation and osmotic resistance of erythrocytes) in vitro and in vivo. Obestatin inhibited in vitro platelet aggregation in the entire dose range and reduced osmotic resistance of erythrocytes in all doses except 300 nmol/kg (obestatin in a dose of 300 nmol/kg had no effect on this parameter). Similar to the results of in vitro experiments, intranasal, intraperitoneal, and subcutaneous administration of obestatin in a dose of 300 nmol/kg inhibited platelet aggregation and had no effect on the osmotic resistance of erythrocytes.

Single exposure of white outbred rats to electromagnetic radiation with a frequency 905 MHz (GSM frequency) for 2 h increased anxiety, reduced locomotor, orientation, and exploration activities in females and orientation and exploration activities in males. Glucocorticoid levels and antioxidant system activity increased in both males and females. In addition to acute effects, delayed effects of radiation were observed in both males and females 1 day after the exposure. These results demonstrated signifi cant effect of GSM-range radiation on the behavior and activity of stress-realizing and stress-limiting systems of the body.

This paper considers the transgenerational effects of prenatal stress of different etiology. The impacts of stress factors on the biochemical and morphofunctional parameters of life of the mother, fetus, and offspring in the first and subsequent generations (F1–F4) are estimated. Particular attention is paid to assessing changes in the parameters of physical development, the state of the hypothalamic-pituitary-adrenal axis, proinflammatory status, behavioral indicators, cognitive performance, and vegetative balance in the poststress period. Contemporary concepts of possible mechanisms of transgenerational transmission of the effects of prenatal stress are considered.

This study analyses the spontaneous behavior and anxiety-phobic status of mature rats that were subjected to antenatal intermittent hypoxia during the early stages of organogenesis. Antenatal intermittent hypoxia caused a decrease of motor activity as well as an enhanced anxiety level in rats of both sexes, while males appeared to be more sensitive to hypoxic influence. The effects of single antenatal intermittent hypoxia were more expressed than those of double exposure.

We studied the effects of a single immobilization stress on pregnant (9th or 10th day of pregnancy) and nonpregnant female rats in the early post-stress period (1 day after a stress). We analyzed the changes in behavioral responses, activity of antioxidant systems (ASs), and GABA metabolism. It was shown that control unstressed pregnant rats had a higher level of locomotor and exploratory activities and a lower level of anxiety and emotional tension as compared to nonpregnant rats. The pregnant rats were characterized by a higher activity of glutamate decarboxylase (GDC). In nonpregnant rats in the early post-stress period, the locomotor and exploratory activity and “risk behavior” increased, while anxiety decreased. These changes were not related to changes in the GABA metabolism, while the efficacy of ASs was increased. In the group of pregnant rats, the consequences of immobilization included only a significant increase in the activity of GABA transaminase (GABA-T). Thus, pregnant rats had higher stress resistance than the nonpregnant rats, according to behavioral indices and activities of systems of GABA metabolism and ASs.

Acute progestational hypoxia induced hyperactivity with low anxiety level and bradycardia in female descendants only. The experimental males demonstrated a significant increase in the duration and frequency of contractions of lymphatic vessels following NE application, while females showed no difference compared to the control.

Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats.

The survival rate, physical development, and spontaneous behavior has been evaluated in pups of albino rats exposed to acute hypobaric hypoxia on the 9–10th day of gestation corresponding to the onset of organogenesis. Prenatal hypoxia increased the mortality among the offspring, delayed their physical development, and affected their spontaneous behavior up to the age of 2 months. The females exposed to intrauterine hypoxia proved to be more sensitive to hypoxia than males.

Ante- and postnatal hypoxia significantly worsened the postnatal development of animals. The posthypoxic behavioral model included hyperactivity and decreased learning ability, these being typical manifestations of attention deficit disorder. A peptide constellation prevented and significantly improved posthypoxic postnatal development and eliminated the majority of negative behavioral changes.

Obestatin is an endogenous regulator of appetite with anorexigenic action. In this study, we analyzed the effects of single and chronic intranasal administra� tions of obestatin or its fragment (1–4) at a dose of 300 nmol/kg on the glucose content of blood and food and water motivation under the conditions of depriva�

We studied the effects of anorectic peptide obestatin and its fragment (1-4) on the antioxidant defense system in animals with normal and experimentally induced increased body weight. In rats with normal body weight, no changes in activity of the antioxidant defense system 1 week after single administration of the substances. After chronic administration of obestatin and fragment (1-4) for 1 week, total antioxidant capacity of the plasma decreased; obestatin also lowered the content of TBA-reactive products. In the overweight rats, SOD-like activity in the plasma increased 1 week after chronic administration of obestatin. Hence, obestatin and its fragment (1-4) induced changes in the antioxidant defense system only after chronic administration.

Acute hypobaric hypoxia of pregnant rats led to a significant delay in body weight gain, growth and time of eye opening in newborn rat pups which was paralleled by behavioral changes. Preventive intranasal instillations of peptide mixture (semax and β-casomorphine-7) to pregnant females prevented the effect of hypoxia on the progeny.

The influence of antenatal intermittent normobaric hypoxia during early organogenesis (days 9–10 of intrauterine development) on the physical development, vegetative balance, and antioxidant defense system of 60-day-old rats was studied. Antenatal exposure to intermittent hypoxia resulted in the impaired physical development of all offspring during the early 15-day postnatal period and caused changes in the vegetative balance of heart regulation, which were differently directed in males and females. Moreover, females that survived antenatal hypoxia had a decreased superoxide dismutase activity in the brain, compared to that in the control rats.

Various ECG characteristics are investigated in white rats subjected to acute hypobaric hypoxia on the 9th–10th day of gestation corresponding to the period of organogenesis. The hypoxia-induced changes in the ECG characteristics are different in groups with a low, middle, and high resistance to acute hypoxia.

Cardiac activity in rats during the postnatal period was studied in vitro and in vivo after exposure of rat pups to antenatal acute hypobaric hypoxia at the stage of organogenesis (day 9-10 of gestation). Cultured cardiomyocytes from rat pups exposed to antenatal hypoxia were characterized by increased rate of contractions and decreased reactivity to norepinephrine. Heart rate elevation, predominance of sympathetic influences on cardiac activity, and significant increase in norepinephrine concentration in the cerebral cortex were found in freely moving animals exposed to antenatal hypoxia. Our results indicate that hypoxia at the stage of organogenesis modulated cardiac activity during the postnatal period, which manifested at the level of effector structures in the heart and activity of regulatory systems.

Changes in ECG parameters were studied in pregnant rats exposed to acute hypobaric hypoxia during the period of organogenesis (gestation days 9 to 10). Rats with low, medium, and high tolerance to hypoxia exhibited pronounced autonomic nervous system imbalance, which become apparent as a loss of correlation between various parameters of ECG signals recorded at rest and during exposure to some stress factors existing under normal conditions.

We studied the effect of exposure to acute hypobaric hypoxia in the progestational period on the content of biogenic amines in the brainstem and cerebral cortex in rat pups of different age. The possibility of correcting hypoxia-induced changes with regulatory peptides was evaluated. We found that early antenatal hypoxia disturbs maturation of catecholaminergic systems in the brain. It should be emphasized that the differences from the control varied depending on the age of rat pups. Single intranasal administration of Semax heptapeptides and β-casomorphine-7 to pregnant females prevented changes in the content of biogenic amines in CNS of the offspring during postnatal ontogeny.

We studied changes in the autonomic balance of heart regulation (by the parameters of heart rate variability) in non-pregnant female rats and rats on the days 10-11 of pregnancy on the next day after stress provoked by acute hypobaric hypoxia, intermittent normobaric hypoxia, or immobilization. The same parameters were assessed in 36-day-old offspring. In non-pregnant rats, the intermittent hypoxia resulted in a shift of the autonomic balance of heart regulation towards activation of the parasympathetic nervous system; in pregnant females, immobilization led to a shift of the autonomic balance towards the sympathetic nervous system. In the offspring, the changes also depended on the type of stress.

We studied the effect of acute hypobaric hypoxia in early organogenesis on physiological and behavioral parameters of second-generation albino rats. Antenatal acute hypoxia was followed by physical and sexual retardation, increase in the mortality rate, and behavioral changes in second-generation animals (hypoactivity of males and females on day 22 of life and hyperactivity of males on day 57 of life). Second-generation animals exhibited no gender differences in body weight and horizontal and vertical locomotor activity.

The effects of Semax heptapeptide on the resistance to acute hypobaric hypoxia and on hypoxic changes in the ECG chronotropic index were studied in 14- and 21-day-old pups. The resistance to hypoxia decreased with age. Hypoxic exposure caused bradycardia in both age groups. Semax reduced the bradycardiac reaction and exerted an antiarrhythmic effect without affecting the resistance to hypoxia.

We studied the effect of acute antenatal hypoxia during the stages of progestation and early organogenesis on some ECG parameters and level of biogenic amines in brain structures in rats. The effect of acute hypoxic exposure during the organogenesis period on the studied parameters was more pronounced than the effect of acute hypoxic exposure during the progestation period. The shift of the autonomic balance towards the sympathetic regulation of cardiac activity is linked with increased content of biogenic amines in the brain stem and cortical structures.

Delayed consequences of acute hypoxia were studied in 60-day-old rat pups. The animals were exposed to acute hypobaric hypoxia on day 10 of embryogenesis. The offspring of intact females served as the control. Reactivity of mesenteric lymphatic vessels to norepinephrine was studied by vital microscopy. The frequency and duration of lymphatic vessel contractions in males significantly increased compared to the control. In females the duration of norepinephrine-induced lymphatic vessel contractions increased, while the frequency and amplitude of contractions and basal vascular tone did not differ from the control.