Laboratory of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
Mol Med Rep. 2012 Nov;6(5):967-72. doi: 10.3892/mmr.2012.1041. Epub 2012 Aug 21.
Excessive corticosterone (CORT) is acknowledged to induce neuronal damage in a number of regions of the brain, particularly the hippocampus, the main area implicated in depression. However, little research has been conducted on alterations to hypothalamic neurons in depression and the cellular and molecular basis for these changes. In the present study, we aimed to determine whether CORT causes apoptosis in primary cultured hypothalamic neurons, and to investigate the protective effects of icariin, an active natural ingredient from the Chinese plant, Epimedium sagittatum Maxim. Our study demonstrates that exposure of hypothalamic neurons to CORT causes a significant loss in viability, a significant decrease in mitochondrial membrane potential, an increase in caspase-3 activity, an elevation in intracellular reactive oxygen species elevation and decreased superoxide dismutase activity. However, pretreatment of cells with icariin prior to CORT exposure was identified to noticeably suppress these CORT-induced events. Furthermore, icariin may prevent CORT-induced cell death via activation of the PI3-K/Akt pathway. In conclusion, icariin is able to prevent CORT-induced hypothalamic cell apoptosis via activation of the PI3-K/Akt pathway.
过量的皮质酮（CORT）被认为会导致大脑的许多区域，特别是海马体，即与抑郁有关的主要区域的神经元损伤。然而，关于抑郁时下丘脑神经元的改变以及这些改变的细胞和分子基础的研究很少。在本研究中，我们旨在确定 CORT 是否会引起原代培养的下丘脑神经元凋亡，并研究淫羊藿苷（一种来自中国植物淫羊藿的活性天然成分）的保护作用。我们的研究表明，CORT 暴露会导致下丘脑神经元的活力显著丧失、线粒体膜电位显著降低、caspase-3 活性增加、细胞内活性氧水平升高和超氧化物歧化酶活性降低。然而，在 CORT 暴露前用淫羊藿苷预处理细胞可明显抑制这些 CORT 诱导的事件。此外，淫羊藿苷可能通过激活 PI3-K/Akt 通路来预防 CORT 诱导的细胞死亡。总之，淫羊藿苷能够通过激活 PI3-K/Akt 通路来预防 CORT 诱导的下丘脑细胞凋亡。
