title: U-shape suppressive effect of phenol red on the epileptiform burst activity via activation of estrogen receptors in primary hippocampal culture.
abstract: Phenol red is widely used in cell culture as a pH indicator. Recently, it also has been reported to have estrogen-like bioactivity and be capable of promoting cell proliferation in different cell lines. However, the effect of phenol red on primary neuronal culture has never been investigated. By using patch clamp technique, we demonstrated that hippocampal pyramidal neurons cultured in neurobasal medium containing no phenol red had large depolarization-associated epileptiform bursting activities, which were rarely seen in neurons cultured in phenol red-containing medium. Further experiment data indicate that the suppressive effect of the phenol red on the abnormal epileptiform burst neuronal activities was U-shape dose related, with the most effective concentration at 28 µM. In addition, this concentration related inhibitory effect of phenol red on the epileptiform neuronal discharges was mimicked by 17-β-estradiol, an estrogen receptor agonist, and inhibited by ICI-182,780, an estrogen receptor antagonist. Our results suggest that estrogen receptor activation by phenol red in the culture medium prevents formation of abnormal, epileptiform burst activity. These studies highlight the importance of phenol red as estrogen receptor stimulator and cautions of careful use of phenol red in cell culture media.
authors.affiliation: Neurology Department, Zhongshan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Ben
authors.initials: B
authors.lastname: Chen
authors.forename: Lulan
authors.initials: L
authors.lastname: Chen
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Ren
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D000077267:Fulvestrant; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010637:Phenolsulfonphthalein / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D010637:Phenolsulfonphthalein
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