Effect of anorexigenic peptide obestatin on platelet aggregation and osmotic resistance of erythrocytes.

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.

Effects of GSM-Frequency Electromagnetic Radiation on Some Physiological and Biochemical Parameters in Rats.

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 significant effect of GSM-range radiation on the behavior and activity of stress-realizing and stress-limiting systems of the body.

Consequences of the α-ketoglutarate dehydrogenase inhibition for neuronal metabolism and survival: implications for neurodegenerative diseases.

Neurodegenerative diseases are accompanied by reduced activity of mitochondrial α-ketoglutarate dehydrogenase multienzyme complex (KGDHC). We present a new cellular model to study molecular mechanisms of this association. By application of the highly specific and efficient inhibitor of KGDHC, succinyl phosphonate (SP), to cultured neurons, we characterized the concentration- and time-dependent consequences of decreased KGDHC activity for neuronal metabolism and viability. Metabolic profiling of SP-treated neurons established accumulation of α-ketoglutarate and pyruvate as indicators of the KGDHC inhibition and ensuing impairment of pyruvate oxidation in the tricarboxylic acid cycle. Concomitant increases in alanine, glutamate and γ-aminobutyrate indicated a scavenging of the accumulated pyruvate and α-ketoglutarate by transamination and further decarboxylation of glutamate. Changes among other amino acids were in accordance with their potential to react with α-ketoglutarate or products of its transamination and serve as fuel compensating for the KGDHC block. Disturbances in neuronal amino acid pool were accompanied by changed polyamines, decreased total protein and increased thymine, suggesting increased catabolism of amino acids to decrease translation and affect DNA turnover/repair. The ensuing ATP salvage was observed as the paradoxical increase in neuronal ATP by mitochondrial inhibitor SP. Extensive exposure of neurons to SP reduced viability, as revealed by both the ATP- and NAD(P)H-dependent viability tests. Thus, we provide experimental evidence on the KGDHC impairment as a cause of neurodegeneration and decipher underlying molecular mechanisms, exposing the key regulatory complex of the tricarboxylic acid cycle as a promising target for directed regulation of neuronal function and survival.

[Transgenerational consequences of acute antenatal stress in pregnant rats].

The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed.

[Changes of glucocorticoid level in plasma and adrenal glands of pregnant rats and their offspring after antenatal stress of different etiology].

We investigated the glucocorticoid level in plasma and adrenal glands of pregnant rats in the period of early organogenesis. Tests were performed 24 hours after stress of different etiology (acute hypobaric hypoxia, intermittent normobaric hypoxia, and immobilization) and then repeated in the adult offspring. There was a significant decrease in the glucocorticoid level in pregnant rats 24 hours after hypoxic stress. Various changes of the basal glucocorticoid level were found in the offspring after antenatal stress. Changes were mostly found in female offspring.

Comparative analysis of the effects of various stress factors at the stage of early organogenesis on heart rate variability in pregnant female rats and their offspring.

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.

[Influence of antenatal intermittent normobaric hypoxia during early organogenesis on the development of white rats].

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.

Transgeneration effects of antenatal acute hypoxia during early organogenesis.

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.

Effect of antenatal hypoxia on age-specific dynamics of ECG parameters and content of biogenic amines in the central nervous system.

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.