References

vavilov

Вавиловский журнал генетики и селекции

Vavilov Journal of Genetics and Breeding

2500-3259

Institute of Cytology and Genetics of Siberian Branch of the RAS

10.18699/VJ16.155

vavilov-586

Research Article

Экспрессия ключевых генов физиологических функций. ОБЗОР

Expression of genes crucial for physiological functions. REVIEW

Глюкокортикоидная гипотеза депрессии: история и перспективы

The glucocorticoid hypothesis of depression: history and perspectives

Шишкина

Г. Т.

Shishkina

G. T.

gtshi@bionet.nsc.ru

Дыгало

Н. Н.

Dygalo

N. N.

Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Россия Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет», Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, RussiaRussian Federation

2016

18052016

202198203

2016

Шишкина Г.Т., Дыгало Н.Н.

Shishkina G.T., Dygalo N.N.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://vavilov.elpub.ru/jour/article/view/586

Нарушение адаптации к неблагоприятным жизненным обстоятельствам считается одной из причин возникновения симптомов депрессии. Согласно глюкокортикоидной гипотезе, важная роль в индукции психоэмоционального расстройства принадлежит стрессорной активации гипоталамо-гипофизарно-адренокортикальной системы (ГГАС). Конечные гормоны этой системы, глюкокортикоиды, принимают важное участие в формировании многих физиологических и поведенческих ответов на стресс. И хотя острый гормональный ответ ГГАС на относительно непродолжительное воздействие обеспечивает быструю мобилизацию защитных сил организма, способствующую эффективному преодолению потенциально опасной ситуации, длительное повышение уровня гормонов может спровоцировать развитие нежелательных последствий, включающих депрессию. Наибольшее внимание при исследовании механизмов смены эффектов глюкокортикоидов с защитных на повреждающие привлекают глюкокортикоидные рецепторы (ГР). Эти рецепторы широко экспрессируются в мозге. Они являются важными регуляторами транскрипционной активности многих генов, в том числе и традиционно связанных с развитием психоэмоциональных отклонений, например, гена мозгового нейротрофического фактора (Brain Derived Neurotrophic Factor, BDNF). Кроме прямого воздействия на транскрипционную активность генов-мишеней, изменение экспрессии самих ГР в результате действия стрессаи / или глюкокортикоидов может модифицировать функциональные ответы на последующие стимулы. Анализ имеющихся в литературе сведений об эффектах стресса и глюкокортикоидов на экспрессию ГР в гиппокампе – структуре мозга, традиционно считающейся наиболее чувствительной к стрессу и принимающей важное участие в контроле эмоций, в связи с экспрессией BDNF и характером индуцируемых стрессорными и гормональными воздействиями психоэмоциональных ответов послужил целью настоящего обзора.

An abnormality in adaptation to negative life events is considered as one of the main causes of the development of depressive symptoms. According to the corticosteroid receptor hypothesis of depression, stress-induced activation of the hypothalamicpituitary- adrenal (HPA) axis plays an important role in the induction of psycho-emotional disturbances. The end products of this axis, glucocorticoids, are involved in the formation of many physiological and behavioral responses to stress. Although the increase in hormone levels following a short-term intervention is directed towards rapid mobilization of the body’s efforts for overcoming potentially dangerous situation, a long-term exposure to stress or glucocorticoids may have negative consequences for mood or behavior. With respect to mechanisms of changing effects of glucocorticoids from protective to damaging, glucocorticoid receptors (GRs) received most attention. These receptors are widely expressed in the brain. They are important regulators of the transcriptional activities of numerous genes, including the gene for such a plasticity-related protein as the brain-derived neurotrophic factor (BDNF) which has been implicated in psychiatric disorders. In addition to direct effects on gene transcription, changes in expression of GR themselves resulting from stress and/or glucocorticoid effects, in turn can modify the functional responses to subsequent stimuli. The purpose of this review was to analyze available literature data on the effects of stress and glucocorticoids on the expression of GR in the hippocampus, which is traditionally considered as the most sensitive to stress brain structure. The review also addresses the implication of GR and BDNF interplay in the pathogenesis of stress-related disorders.

стрессглюкокортикоидные рецепторыBDNF

stressglucocorticoid receptorsBDNF

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