17β-Oestradiol Protects Primary-Cultured Rat Cortical Neurons from Ketamine-Induced Apoptosis by Activating PI3K/Akt/Bcl-2 Signalling.
作者： Jianli Li , Honghai Wu , Gai Xue , Pei Wang , Yanning Hou
DOI: 10.1111/BCPT.12124
关键词: Programmed cell death 、 Neuroactive steroid 、 TUNEL assay 、 Neurodegeneration 、 PI3K/AKT/mTOR pathway 、 Cell biology 、 Viability assay 、 Protein kinase B 、 Neuroprotection 、 Biology
摘要: Numerous studies in rodents have indicated that exposure to ketamine during the period when synaptogenesis is highly active induces neurodegeneration. Thus, there a growing need develop strategies prevent ketamine-induced brain injury developing brain. Oestradiol neuroactive steroid prevents neuronal cell death different experimental models by activating survival signals and inhibiting apoptotic signals. The main goal of this study was investigate neuroprotective effects 17β-oestradiol against neurodegeneration primary-cultured cortical neurons. data revealed (0.1 μM) combination with (100 μM) increased viability MTT assay reduced number cells detected TUNEL Hoechst 33258 staining. To elucidate possible mechanism which exerts its effect, we investigated PI3K pathway using an inhibitor PI3K, LY294002. protective were abrogated Furthermore, found not only induced phosphorylation substrate Akt, but also expression Bcl-2, down-regulated caspase-3 activity inhibited apoptosis. These demonstrate effect apoptosis PI3K/Akt/Bcl-2 signalling pathway. Therefore, appears be promising agent preventing or reversing ketamine's toxic on neurons at early developmental stage.
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