title: 17β-Oestradiol Protects Primary-Cultured Rat Cortical Neurons from Ketamine-Induced Apoptosis by Activating PI3K/Akt/Bcl-2 Signalling.
abstract: Numerous studies in rodents have indicated that exposure to ketamine during the period when synaptogenesis is highly active induces neurodegeneration. Thus, there is a growing need to develop strategies to prevent ketamine-induced brain injury in the developing brain. Oestradiol is a neuroactive steroid that prevents neuronal cell death in different experimental models by activating cell survival signals and inhibiting apoptotic signals. The main goal of this study was to investigate the neuroprotective effects of 17β-oestradiol against ketamine-induced apoptotic neurodegeneration in primary-cultured cortical neurons. The data revealed that 17β-oestradiol (0.1 μM) in combination with ketamine (100 μM) increased cell viability in the MTT assay and reduced the number of apoptotic cells detected by TUNEL and Hoechst 33258 staining. To elucidate a possible mechanism by which 17β-oestradiol exerts its neuroprotective effect, we investigated the PI3K pathway using an inhibitor of PI3K, LY294002. The protective effects of 17β-oestradiol were abrogated by LY294002. Furthermore, we found that 17β-oestradiol not only induced phosphorylation of the PI3K substrate Akt, but also increased the expression of Bcl-2, which down-regulated ketamine-induced caspase-3 activity and inhibited neuronal apoptosis. These data demonstrate that 17β-oestradiol exerts a neuroprotective effect against ketamine-induced neuronal apoptosis by activating the PI3K/Akt/Bcl-2 signalling pathway. Therefore, 17β-oestradiol appears to be a promising agent in preventing or reversing ketamine's toxic effects on neurons at an early developmental stage.
authors: Hebei Medical University, Shijiazhuang, Hebei Province, China.|Hebei General Hospital, Shijiazhuang, Hebei Province, China.
authors: Jianli
authors: J
authors: Li
authors: Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang, Hebei Province, China.
authors: Honghai
authors: H
authors: Wu
authors: Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang, Hebei Province, China.
authors: Gai
authors: G
authors: Xue
authors: Hebei General Hospital, Shijiazhuang, Hebei Province, China.
authors: Pei
authors: P
authors: Wang
authors: Hebei Medical University, Shijiazhuang, Hebei Province, China.|Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang, Hebei Province, China.
authors: Yanning
authors: Y
authors: Hou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D007649:Ketamine / Q000009:adverse effects / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D053148:Caspase 3; D002867:Chromones; D004958:Estradiol; D007649:Ketamine; D009025:Morpholines; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one