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Nauchno-prakticheskii zhurnal «Patogenez»
Article . 2018 . Peer-reviewed
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Dipeptidyl peptidase IV inhibitors diprotin A and sitagliptin administered in the first postnatal week change the level of monoamines and their metabolites in the brain of adult rats

Ингибиторы дипептидилпептидазы-IV дипротин А и ситаглиптин, вводимые в первую постнатальную неделю развития, изменяют уровень моноаминов и их метаболитов в мозге взрослых крыс
Authors: N. N. Khlebnikova; V. S. Kudrin; N. A. Krupina; V. B. Narkevich; P. L. Naplyokova;

Dipeptidyl peptidase IV inhibitors diprotin A and sitagliptin administered in the first postnatal week change the level of monoamines and their metabolites in the brain of adult rats

Abstract

В наших предыдущих исследованиях установлено, что у крысят, подвергнутых действию ингибиторов дипептидилпептидазы IV (ДП-IV) дипротина А и ситаглиптина в период с 5 по 18 постнатальные дни (ПНД) или с 1 по 7 ПНД, во взрослом возрасте развивается тревожно-депрессивное состояние c повышенной стресс-провоцируемой агрессией. Нарушения поведения, вызванные действием ингибиторов ДП-IV на второй - третьей неделях постнатального развития, сопровождаются изменениями функционирования моноаминергических систем мозга в структурах, опосредующих эмоционально-мотивационную деятельность. Целью настоящего исследования было изучение уровня моноаминов и их метаболитов в мозге взрослых крыс, подвергнутых действию дипротина А и ситаглиптина в ПНД 1-7. Методы. Крысятам опытных групп внутрибрюшинно вводили дипротин А (2 мг/кг) или ситаглиптин (4 мг/кг), животным контрольной группы - физиологический раствор. У крыс в возрасте 2,5 мес. методом ВЭЖХ/ЭД оценивали уровень моноаминов и их метаболитов во фронтальной коре, стриатуме, миндалине, гиппокампе и гипоталамусе. Результаты. У крыс обеих опытных групп обнаружено снижение уровня серотонина во фронтальной коре и норадреналина в стриатуме. Кроме того, у животных, которым неонатально вводили дипротин А, повышался оборот серотонина во фронтальной коре и миндалине. Заключение. Данные свидетельствуют о том, что действие ингибиторов ДП-IV в ПНД 1-7 вызывает длительную дисфункцию моноаминергических систем мозга крыс. In our previous studies, we have shown that rat pups exposed to dipeptidyl peptidase IV (DP-IV) inhibitors during postnatal days (PND) 5-18 or PND 1-7, in adulthood develops anxiety-depressive state with stress-induced aggression. Behavioral disorders in adult rats caused by the action of DP-IV inhibitors in the second - third postnatal weeks are accompanied by changes in monoamine metabolism in the striatum. The aim of this study was to estimate the levels of monoamines and their metabolites in brain structures of adult rats exposed to diprotin A and sitagliptin at PND 1-7. Methods. Diprotin A (2 mg/kg) or sitagliptin (4 mg/kg) was administered intraperitoneally to rats of the experimental group, and physiological saline - to the control animals. The levels of monoamines and their metabolites were measured by the HPLC/ED in the frontal cortex, striatum, amygdala, hippocampus and hypothalamus in 2,5-months-old animals. Results. We revealed a significant decrease in the level of serotonin in the frontal cortex and norepinephrine in the striatum. In addition, diprotin A increased serotonin turnover in the frontal cortex and amygdala. Conclusion The data suggest that the action of DP-IV inhibitors at PND 1-7 induces long-term dysfunction of monoaminergic systems of the rat’s brain.

Keywords

rats, model of an anxiety-depressive state, inhibitor of dipeptidyl peptidase-IV, postnatal days 1-7, модель тревожно-депрессивного состояния, monoamines in brain structures, крысы, моноамины в структурах мозга, ингибиторы дипептидилпептидазы-IV

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
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