Acta physiologica (Oxford, England) · 2018
Dorsal hypothalamic dopaminergic neurons play an inhibitory role in the hypothalamic-pituitary-adrenal axis via activation of D2R in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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.
Di Tingting, Chen Peipei, Yuan Zihao, Wang Ya, Sha Sha, Chen Ling
Аннотация
AIM: The present study investigated the effects of dorsal hypothalamic dopamine (dh-DA) neurons on activation of hypothalamic-pituitary-adrenal (HPA) axis in adult male mice.
METHODS: Tyrosine hydroxylase-labelled DA neurons, DA content, c-Fos immune-positive (c-Fos+) cells and CRH expression in paraventricular nuclei (PVN), serum CORT and ACTH were examined at 4-, 8-, and 12-hour after a signal injection of MPTP (20 mg kg-1 ) respectively.
RESULTS: The dh-DA neurons and DA content in PVN at 4-hour post-MPTP were reduced with recovery at 12-hour post-MPTP, while decline of nigrostriatal DA neurons and DA content in striatum started from 12-hour post-MPTP. Number of c-Fos+ cells, and CORT/ACTH levels increased at 4-hour post-MPTP, followed by recovery at 12-hour post-MPTP. The CRH mRNA was elevated at 4-hour post-MPTP, and sustained for over 12 hours. At 2-hour post-MPTP, PVN-injection of D2R agonist quinpirole corrected the increases in c-Fos+ cells, CORT/ACTH and CRH mRNA, but D1R agonist SKF38393 did not. PVN-injection of D2R antagonist L-sulpiride alone caused increases in c-Fos+ cells, CORT/ACTH and CRH mRNA. Similarly, PVN-injection of CB1R agonist WIN552,12 prevented the increases in c-Fos+ cells and CORT/ACTH rather than CRH mRNA, which were blocked by CB1R antagonist AM251. Levels of PKA and CREB phosphorylation in PVN were increased at 4-hour post-MPTP, which were blocked by quinpirole, but not WIN552,12. PKA inhibitor H89 corrected the increase of CRH mRNA at 8-hour post-MPTP.
CONCLUSION: The activation of dh-DA neurons regulates negatively HPA axis through targeting D2Rs of CRH neurons to enhance endocannabinoid release and inhibit PKA-CREB pathway.
METHODS: Tyrosine hydroxylase-labelled DA neurons, DA content, c-Fos immune-positive (c-Fos+) cells and CRH expression in paraventricular nuclei (PVN), serum CORT and ACTH were examined at 4-, 8-, and 12-hour after a signal injection of MPTP (20 mg kg-1 ) respectively.
RESULTS: The dh-DA neurons and DA content in PVN at 4-hour post-MPTP were reduced with recovery at 12-hour post-MPTP, while decline of nigrostriatal DA neurons and DA content in striatum started from 12-hour post-MPTP. Number of c-Fos+ cells, and CORT/ACTH levels increased at 4-hour post-MPTP, followed by recovery at 12-hour post-MPTP. The CRH mRNA was elevated at 4-hour post-MPTP, and sustained for over 12 hours. At 2-hour post-MPTP, PVN-injection of D2R agonist quinpirole corrected the increases in c-Fos+ cells, CORT/ACTH and CRH mRNA, but D1R agonist SKF38393 did not. PVN-injection of D2R antagonist L-sulpiride alone caused increases in c-Fos+ cells, CORT/ACTH and CRH mRNA. Similarly, PVN-injection of CB1R agonist WIN552,12 prevented the increases in c-Fos+ cells and CORT/ACTH rather than CRH mRNA, which were blocked by CB1R antagonist AM251. Levels of PKA and CREB phosphorylation in PVN were increased at 4-hour post-MPTP, which were blocked by quinpirole, but not WIN552,12. PKA inhibitor H89 corrected the increase of CRH mRNA at 8-hour post-MPTP.
CONCLUSION: The activation of dh-DA neurons regulates negatively HPA axis through targeting D2Rs of CRH neurons to enhance endocannabinoid release and inhibit PKA-CREB pathway.