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Psychedelics promote plasticity by directly binding to BDNF receptor TrkBстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 1 января 2025 г.
- Авторы: Moliner Rafael, Girych Mykhailo, Brunello Cecilia A., Kovaleva Vera, Biojone Caroline, Enkavi Giray, Antenucci Lina, Kot Erik F., Goncharuk Sergey A., Kaurinkoski Katja, Kuutti Mirjami, Fred Senem M., Elsilä Lauri V., Sakson Sven, Cannarozzo Cecilia, Diniz Cassiano R.A.F, Seiffert Nina, Rubiolo Anna, Haapaniemi Hele, Meshi Elsa, Nagaeva Elina, Öhman Tiina, Róg Tomasz, Kankuri Esko, Vilar Marçal, Varjosalo Markku, Korpi Esa R., Permi Perttu, Mineev Konstantin S., Saarma Mart, Vattulainen Ilpo, Casarotto Plinio C., Castrén Eero
- Журнал: Nature Neuroscience
- Том: 26
- Номер: 6
- Год издания: 2023
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 1032
- Последняя страница: 1041
- DOI: 10.1038/s41593-023-01316-5
- Аннотация: Psychedelics produce fast and persistent antidepressant efects and induce neuroplasticity resembling the efects of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fuoxetine and ketamine, act by binding to TrkB, the receptor for BDNF. Here we show that lysergic acid diethylamide (LSD) and psilocin directly bind to TrkB with afnities 1,000-fold higher than those for other antidepressants, and that psychedelics and antidepressants bind to distinct but partially overlapping sites within the transmembrane domain of TrkB dimers. The efects of psychedelics on neurotrophic signaling, plasticity and antidepressant-like behavior in mice depend on TrkB binding and promotion of endogenous BDNF signaling but are independent of serotonin 2A receptor (5-HT2A) activation, whereas LSD-induced head twitching is dependent on 5-HT2A and independent of TrkB binding. Our data confrm TrkB as a common primary target for antidepressants and suggest that high-afnity TrkB positive allosteric modulators lacking 5-HT2A activity may retain the antidepressant potential of psychedelics without hallucinogenic efects.
- Добавил в систему: Кот Эрик Федорович