17β-Estradiol Protects Neural Stem/Progenitor Cells Against Ketamine-Induced Injury Through Estrogen Receptor β Pathway.
17β-Estradiol Protects Neural Stem/Progenitor Cells Against Ketamine-Induced Injury Through Estrogen Receptor β Pathway.
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DOI：
10.3389/fnins.2020.576813
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发表时间：
2020
影响因子：
4.3
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Li W;Lu P;Lu Y;Wei H;Niu X;Xu J;Wang K;Zhang H;Li R;Qiu Z;Wang N;Jia P;Zhang Y;Zhang S;Lu H;Chen X;Liu Y;Zhang P
氯胺酮抑制神经干/祖细胞（NSPC）增殖，破坏发育中大脑的正常神经发生。17β-雌二醇减轻氯胺酮给药后的神经发生损伤并增强行为表现。然而，17β-雌二醇的受体途径保护NSPC免受氯胺酮诱导的损伤仍然未知。本研究探讨了雌激素受体α（ER-α）和雌激素受体β（ER-β）在17β-雌二醇（E2）对氯胺酮（Ketamine）暴露的NSPCs的保护作用中的作用及其可能机制。用氯胺酮和不同剂量的ER-α激动剂4，4 ′，4 ″-（4-丙基-[1H]-吡唑-1，3，5-三基）三酚（PPT）或ER-β激动剂2，3-双（4-羟基苯基）丙腈（DPN）处理原代培养的NSPCs 24 h。通过5-溴-2-脱氧尿苷掺入试验分析NSPC增殖。Western blotting检测磷酸化糖原合成酶激酶-3 β（p-GSK-3β）的表达。结果发现，不同浓度的PPT处理并不改变氯胺酮对NSPC增殖的抑制作用。氯胺酮对NSPC增殖的抑制作用在染毒后24 h明显减弱（P < 0.05）。此外，DPN处理增加了暴露于氯胺酮的NSPCs中p-GSK-3β的表达。提示ER-β可能介导了17β-雌二醇对氯胺酮损伤的NSPC增殖的保护作用，GSK-3β参与了这一过程
Ketamine inhibits neural stem/progenitor cell (NSPC) proliferation and disrupts normal neurogenesis in the developing brain. 17β-Estradiol alleviates neurogenesis damage and enhances behavioral performance after ketamine administration. However, the receptor pathway of 17β-estradiol that protects NSPCs from ketamine-induced injury remains unknown. In the present study, we investigated the role of estrogen receptor α (ER-α) and estrogen receptor β (ER-β) in 17β-estradiol’s protection against ketamine-exposed NSPCs and explored its potential mechanism. The primary cultured NSPCs were identified by immunofluorescence and then treated with ketamine and varying doses of ER-α agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) or ER-β agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) for 24 h. NSPC proliferation was analyzed by 5-bromo-2-deoxyuridine incorporation test. The expression of phosphorylated glycogen synthase kinase-3β (p-GSK-3β) was quantified by western blotting. It was found that treatment with different concentrations of PPT did not alter the inhibition of ketamine on NSPC proliferation. However, treatment with DPN attenuated the inhibition of ketamine on NSPC proliferation at 24 h after their exposure (P < 0.05). Furthermore, treatment with DPN increased p-GSK-3β expression in NSPCs exposed to ketamine. These findings indicated that ER-β mediates probably the protective effects of 17β-estradiol on ketamine-damaged NSPC proliferation and GSK-3β is involved in this process
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通讯作者：
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