Влияние неонатального введения дексаметазона на когнитивные способности взрослых самцов мышей и экспрессию генов в гипоталамусе

Ранний постнатальный период является критическим для развития нервной системы. Стресс в этот период вызывает негативные отдаленные последствия, которые отражаются как на поведенческом, так и на молекулярном уровне. В нашем исследовании для моделирования повышенного уровня глюкокортикоидов, характерного для стрессирующего воздействия в раннем возрасте, мы использовали введение дексаметазона, агониста глюкокортикоидных рецепторов, в понижающихся дозах в первые три дня жизни (0.5, 0.3, 0.1 мг/кг, п/к). У взрослых самцов мышей с неонатальным введением дексаметазона было найдено увеличение относительного веса надпочечников и снижение веса тела, при этом базальный уровень кортикостерона в крови не изменялся. Введение дексаметазона в раннем возрасте оказало негативное воздействие на скорость обучения и формирование пространственной памяти в водном лабиринте Морриса у взрослых животных. Мы проанализировали влияние повышенного уровня глюкокортикоидов в раннем возрасте на экспрессию генов Crh, Avp, Gr, Mr, участвующих в регуляции гипоталамо-гипофизарно-надпочечниковой системы (ГГНС), в гипоталамусе взрослых животных. Уровень экспрессии гена минералокортикоидного рецептора (Mr) был снижен достоверно, а гена глюкокортикоидного рецептора (Gr) – на уровне тенденции (р = 0.058) у самцов мышей с неонатальным введением дексаметазона по сравнению с введением физиологического раствора. Уровень экспрессии гена, кодирующего кортикотропин-рилизинг гормон (Crh), не изменялся, тогда как экспрессия гена вазопрессина (Avp) повышалась под влиянием неонатального введения дексаметазона. Полученные данные демонстрируют возможное нарушение механизмов негативной регуляции ГГНС на уровне гипоталамуса, в которую вовлечены глюкокортикоидный и минералокортикоидный рецепторы. Нарушение функции ГГНС при активации глюкокортикоидной системы в раннем возрасте может быть причиной развития когнитивных нарушений у взрослых животных. 

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