AUTHOR=Li Weisong , Lu Pan , Lu Yang , Wei Haidong , Niu Xiaoli , Xu Jing , Wang Kui , Zhang Hong , Li Rong , Qiu Zhengguo , Wang Ning , Jia Pengyu , Zhang Yan , Zhang Shuyue , Lu Haixia , Chen Xinlin , Liu Yong , Zhang Pengbo 

TITLE=17β-Estradiol Protects Neural Stem/Progenitor Cells Against Ketamine-Induced Injury Through Estrogen Receptor β Pathway

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 14 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.576813

DOI=10.3389/fnins.2020.576813

ISSN=1662-453X

ABSTRACT=Ketamine inhibits neural stem cell (NSC) proliferation and disturbs normal neurogenesis in the developing brain. 17β-estradiol attenuates neurogenesis damage and improves behavior performance following ketamine exposure. However, the receptor pathway of 17β-estradiol protects NSCs 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 NSCs and explored its potential mechanism. The primary cultured NSCs 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 24h. NSC proliferation was analyzed by 5-Bromo-2-deoxyUridine (BrdU) 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 concentration of PPT did not alter the inhibition of ketamine on NSC proliferation.  However, treatment with DPN attenuated the inhibition of ketamine on NSC proliferation at 24h following their exposure (P<0.05). Furthermore, treatment with DPN increased p-GSK-3β expression in NSCs exposed to ketamine. These findings indicated that ER-β may mediate the protective effects of 17β-estradiol on ketamine-damaged NSCs proliferation and GSK-3β is involved in this process