Fetal or newborn hypoxia is a major cause of neonatal mortality and induces long-term motor and cognitive impairment. The aim of the presented work was to study the effects of an acute normobaric hypoxia in rats at the age of 10 days (a model of full-term human pregnancy). Male and female Wistar rats were exposed to hypoxic condition (oxygen content – 8 % for 2 h). Control animals were kept in the same conditions with normal oxygen content. From 11 to 35 days of life, the level of physical and motor development, motor and exploratory activity, and the level of anxiety were assessed. During hypoxic exposure the level of lethality was 21.1%. In rats of both sexes, there was a slowdown in weight gain and retarded performance of motor reflexes. Impaired motor coordination and ability to keep balance were recorded in male, but not in female rats underwent neonatal hypoxia. Adolescent female rats subjected to hypoxia demonstrated increased anxiety-like behaviour in elevated plus maze test. The results obtained indicate the gender-specific manner of the effects of neonatal hypoxia. The described method can be considered as a model of hypoxic brain damage in full-term newborns.

В целях исследования молекулярных механизмов действия пептидов меланокортинового ряда был проведен сравнительный анализ действия семакса и его структурного аналога АКТГ(6-9)PGP на транскриптом гиппокампа крыс в норме и условиях острого стресса с помощью метода RNA-Seq. Полученные результаты выявили общие и специфические эффекты пептидов меланокортинового ряда в регулировании экспрессии генов в условиях острого стресса и нормы. Предложена модель формирования ответа транскриптома на введение пептидов, основанная на аллостерическом взаимодействии пептидов с рецепторами. In order to study the molecular mechanisms of action of the peptides of the melanocortin series, a comparative analysis of the effect of Semax and its structural analogue of ACTH(6-9)PGP on transcripts of rat hippocampus under normal and acute stress conditions was performed using the RNA-Seq method. The results revealed common and specific effects of peptides in the regulation of gene expression under acute stress and normal conditions. We proposed a model for the formation of transcriptome response to peptide administration based on allosteric interaction of peptides with receptors.

Melanocortins (MCs) have a wide spectrum of physiological activity. All native MCs have a core pharmacophore structure of tetrapeptide His-Phe-Arg-Trp sequence, corresponding to ACTH6-9 fragment. The sequence is necessary for activation of all subtypes of MC receptors, but the tetrapeptide has poor potency and selectivity. It was shown earlier that the addition of proline-rich sequences to natural peptides led to enhancing and prolongation of their neurotropic effects. An example of such a compound is fragment ACTH4-10 analog with prolong neurotropic effects heptapeptide Semax (ACTH4-7Pro-Gly-Pro). The work is devoted to the research of the effects of a synthetic peptide comprising the natural ACTH6-9 sequence and the fragment PGP in its structure – ACTH6-9PGP (HFRWPGP). The peptide effects on the learning ability and anxiety level were studied in white rats. The peptide was injected intranasally at a dose of 0.05 mg/kg 15 min or 20 h before the experiment. It was shown that heptapeptide ACTH6-9PGP improved the acquisition of food-motivated maze task and retention of passive avoidance task, and also it exhibited an anxiolytic activity in elevated plus maze test when injected 15 min before testing. The peptide administration 20 h before testing did not lead to changes in learning parameters and anxiety level in comparison to control animals. Thus, the peptide the structure of which includes ACTH6-9 fragment and tripeptide PGP has nootropic and anxiolytic activity. Consequently, the spectrum of neurotropic activity of ACTH6-9PGP coincides with the spectrum of Semax activity, but the duration of its effects is much shorter.

Изучено влияние семакса на формирование условной реакции активного избегания у крыс в различных экспериментальных моделях. Установлено, что внутрибрюшинное введение семакса в дозе 0.05 мг/кг ускоряет выработку условной реакции одностороннего избегания в модели выработки рефлекса активного избегания болевого раздражителя прыжком на полку. При обучении животных в челночной камере пептид повышает пороговое значение тока, необходимое для провокации перемещения крыс по камере, и замедляет выработку реакции двустороннего активного избегания. При этом семакс стимулирует воспроизведение реакции избегания в челночной камере у крыс после функциональных нарушений, вызванных экстренным изменением причинно-следственных и пространственных отношений в экспериментальной среде. Полученные данные подтверждают наличие у пептида ноотропных свойств.