vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ16.149vavilov-585Research ArticleЭкспрессия ключевых генов физиологических функций. ОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕExpression of genes crucial for physiological functions. ORIGINAL ARTICLEВлияние раннего провоспалительного стресса на экспрессию различных транскриптов BDNF в отделах мозга самцов крыс препубертатного возрастаEffects of early neonatal proinflammatory stress on the expression of BDNF transcripts in the brain regions of prepubertal male ratsПерегудД. И.PeregudD. I.peregud_d@yahoo.comФрейманС. В.FreimanS. V.ТишкинаА. О.TishkinaA. O.СохраняеваЛ. С.SokhranyaevaL. S.ЛазареваН. А.LazarevaN. A.ОнуфриевМ. В.OnufrievM. V.СтепаничевМ. Ю.StepanichevM. Y.ГуляеваН. В.GulyaevaN. V.Научно-исследовательский институт наркологии – филиал Федерального государственного бюджетного учреждения «Федеральный медицинский исследовательский центр психиатрии и наркологии имени В.П. Сербского» Минздрава России, Москва, Россия Федеральное государственное бюджетное учреждение науки Институт высшей нервной деятельности и нейрофизиологии Российской академии наук, Москва, РоссияРоссияFederal State Budgetary Institution “V. Serbsky Federal Medical Research Centre for Psychiatry and Drug Addiction”, of the Ministry of Health of the Russian Federation, Moscow, Russia Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, RussiaRussian FederationФедеральное государственное бюджетное учреждение науки Институт высшей нервной деятельности и нейрофизиологии Российской академии наук, Москва, Россия Научно-практический центр психоневрологии департамента здравоохранения Москвы, Москва, РоссияРоссияInstitute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia Research and Practice Psychoneurology Centre, Moscow Healthcare Department, Moscow, RussiaRussian FederationФедеральное государственное бюджетное учреждение науки Институт высшей нервной деятельности и нейрофизиологии Российской академии наук, Москва, РоссияРоссияInstitute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, RussiaRussian Federation201618052016202191197Copyright © Перегуд Д.И., Фрейман С.В., Тишкина А.О., Сохраняева Л.С., Лазарева Н.А., Онуфриев М.В., Степаничев М.Ю., Гуляева Н.В., 20162016Перегуд Д.И., Фрейман С.В., Тишкина А.О., Сохраняева Л.С., Лазарева Н.А., Онуфриев М.В., Степаничев М.Ю., Гуляева Н.В.Peregud D.I., Freiman S.V., Tishkina A.O., Sokhranyaeva L.S., Lazareva N.A., Onufriev M.V., Stepanichev M.Y., Gulyaeva N.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/585

Провоспалительный стресс, перенесенный в раннем постнатальном периоде, способен провоцировать нарушение различных типов поведения у взрослых половозрелых особей, при этом механизмы, лежащие в основе данных нарушений, изучены недостаточно. Мозговой нейротрофический фактор (Brain-Derived Neurotrophic Factor, BDNF) играет ключевую роль в реализации нейропластических процессов как в норме, так и при патологии. Ген BDNF транскрибируется в виде экзон-специфических мРНК, которые могут обладать различной реактивностью в зависимости от стимула. Мы предположили, что нарушения экспрессии специфических мРНК BDNF в отделах центральной нервной системы после стресса, вызванного провоспалительными стимулами на ранних этапах онтогенеза, могут составлять один из механизмов последующих расстройств поведения. Целью работы явилось исследование влияния провоспалительного стресса в раннем неонатальном периоде на содержание BDNF на уровне полипептида и паттерн экспрессии экзон-специфических мРНК BDNF в неокортексе и гиппокампе самцов крыс препубертатного возраста. Провоспалительный стресс вызывали путем подкожного введения бактериального липополисахарида детенышам крыс на третий и пятый постнатальные дни, а анализ BDNF проводили в возрасте 36 дней. Концентрацию полипептида BDNF в отделах головного мозга оценивали посредством твердофазного иммуноферментного анализа, экспрессию экзон-специфических мРНК BDNF исследовали с помощью количественной полимеразной цепной реакции после этапа обратной транскрипции. Содержание полипептида BDNF и уровень транскриптов, содержащих общий экзон IX, не менялись в результате провоспалительного стресса. В неокортексе (но не в гиппокампе) крыс, которым вводили липополисахарид, снижался уровень мРНК BDNF, содержащей экзон IV. Изменений в уровне других транскриптов, содержащих экзоны I и VI, не наблюдалось ни в одном из исследованных отделов мозга. Учитывая, что, согласно данным литературы, у животных, перенесших ранний провоспалительный стресс, развиваются нарушения поведения, мы предполагаем, что специфические изменения паттерна экспрессии BDNF могут быть вовлечены в патогенез этих нарушений.

Early postnatal proinflammatory stress provokes behavioral impairments in adulthood; however, underlying mechanisms are still elusive. Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroplastic changes in health as well as at pathology. The BDNF gene is transcribed to exon-specific mRNAs and the pattern of their expression depends on stimulus. We suggest that disturbances of exonspecific BDNF mRNA expression in the brain regions after stress induced by proinflammatory stimuli in early postnatal period could be one of the underlying mechanisms of consequent behavioral impairments. Thus, the aim of the study was to investigate the effects of proinflammatory stress in early postnatal ontogeny on the expression of BDNF and the patterns of expression of the BDNF gene in the neocortex and hippocampus of prepubertal male rats. The proinflammatory stress was induced by subcutaneous administration of bacterial lipopolysaccharide (LPS) to rat pups on postnatal days 3 and 5, while BDNF expression was analyzed in 36-day-old rats. BDNF polypeptide concentration was estimated by means of an enzyme-linked immunosorbent assay, while quantitative polymerase chain reaction followed by reverse transcription was used to detect exon-specific BDNF mRNA expression. The levels of BDNF and transcripts, containing common exon IX were similar in the control and LPS-treated rats. In the rats treated with LPS, the level of BDNF mRNA, containing exon IV, was lower in the neocortex, but not in the hippocampus. No changes in the expression of the transcripts containing exons I and VI were observed in any brain structure studied. We suggest that specific alterations in BDNF expression may be involved in the susceptibility to the development of behavioral impairments of animals subjected to early proinflammatory stress.

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The authors declare that there are no conflicts of interest present.