title: Endogenously expressed estrogen receptors mediate neuroprotection in hippocampal cells (HT22).
abstract: Discovery of estrogen receptors (ER) in the central nervous system and the ability of estrogens to modulate neural circuitry and act as neurotrophic factors, suggest a therapeutic role of this steroid. To gain better understanding of the specificity and cellular mechanisms involved in estrogen-mediated neuroprotection, a mouse hippocampal neuronal cell line (HT22) was evaluated. Earlier reports indicated this cell line was devoid of ERs. Contrary to these findings, characterization of HT22 cells using RT-PCR, immunoblot, immunocytochemical, and radioligand binding techniques revealed endogenous expression of ER. The predominant subtype appeared to be ERalpha with functional activity confirmed using an ERE-tk-luciferase assay. The ability of an ER antagonist, ICI-182780, to block the neuroprotective effects of estrogens confirmed ER was involved mechanistically in neuroprotection. In conclusion, HT22 cells express functional ERalpha or a closely related ER enabling this cell line to be used to profile estrogens for neuroprotective properties acting via an ER-dependent mechanism.
authors.affiliation: Women's Health Research Institute, Wyeth Research, Collegeville, Pennsylvania 19426, USA. deeched@wyeth.com
authors.forename: Darlene C
authors.initials: DC
authors.lastname: Deecher
authors.forename: Pamela
authors.initials: P
authors.lastname: Daoud
authors.forename: Ramesh A
authors.initials: RA
authors.lastname: Bhat
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D002460:Cell Line; D017931:DNA Primers; D004967:Estrogens / Q000502:physiology; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D051379:Mice; D018696:Neuroprotective Agents; D011869:Radioligand Assay; D011960:Receptors, Estrogen / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004967:Estrogens; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D018698:Glutamic Acid