Psychopharmacology · 2016
The role of sigma-1 receptor and brain-derived neurotrophic factor in the development of diabetes and comorbid depression in streptozotocin-induced diabetic rats.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lenart Lilla, Hodrea Judit, Hosszu Adam, Koszegi Sandor, Zelena Dora, Balogh Dora, Szkibinszkij Edgar, Veres-Szekely Apor, Wagner Laszlo, Vannay Adam, Szabo Attila J, Fekete Andrea
Аннотация
RATIONALE: Depression is highly prevalent in diabetes (DM). Brain-derived neurotrophic factor (BDNF) which is mainly regulated by the endoplasmic reticulum chaperon sigma-1 receptor (S1R) plays a relevant role in the development of depression.
OBJECTIVES: We studied the dose-dependent efficacy of S1R agonist fluvoxamine (FLU) in the prevention of DM-induced depression and investigated the significance of the S1R-BDNF pathway.
METHODS: We used streptozotocin to induce DM in adult male rats that were treated for 2 weeks p.o. with either different doses of FLU (2 or 20 mg/bwkg) or FLU + S1R antagonist NE100 (1 mg/bwkg) or vehicle. Healthy controls were also enrolled. Metabolic, behaviour, and neuroendocrine changes were determined, and S1R and BDNF levels were measured in the different brain regions.
RESULTS: In DM rats, immobility time was increased, adrenal glands were enlarged, and thymuses were involuted. FLU in 20 mg/bwkg, but not in 2 mg/bwkg dosage, ameliorated depression-like behaviour. S1R and BDNF protein levels were decreased in DM, while FLU induced SIR-BDNF production. NE100 suspended all effects of FLU.
CONCLUSIONS: We suggest that disturbed S1R-BDNF signaling in the brain plays a relevant role in DM-induced depression. The activation of this cascade serves as an additional target in the prevention of DM-associated depression.
OBJECTIVES: We studied the dose-dependent efficacy of S1R agonist fluvoxamine (FLU) in the prevention of DM-induced depression and investigated the significance of the S1R-BDNF pathway.
METHODS: We used streptozotocin to induce DM in adult male rats that were treated for 2 weeks p.o. with either different doses of FLU (2 or 20 mg/bwkg) or FLU + S1R antagonist NE100 (1 mg/bwkg) or vehicle. Healthy controls were also enrolled. Metabolic, behaviour, and neuroendocrine changes were determined, and S1R and BDNF levels were measured in the different brain regions.
RESULTS: In DM rats, immobility time was increased, adrenal glands were enlarged, and thymuses were involuted. FLU in 20 mg/bwkg, but not in 2 mg/bwkg dosage, ameliorated depression-like behaviour. S1R and BDNF protein levels were decreased in DM, while FLU induced SIR-BDNF production. NE100 suspended all effects of FLU.
CONCLUSIONS: We suggest that disturbed S1R-BDNF signaling in the brain plays a relevant role in DM-induced depression. The activation of this cascade serves as an additional target in the prevention of DM-associated depression.