title: Increased estrogen receptor beta expression correlates with decreased spine formation in the rat hippocampus.
abstract: Estrogens play an important role in the brain function acting through two receptor types, ERalpha and ERbeta, both well-recognized as transcription factors. In this study, we investigated the ERbeta mRNA and protein levels in the rat hippocampus by using two in vivo models that are known to affect synapse formation. Natural estrous-proestrous cycle was used as a model in which a marked decrease in the density of hippocampal synapses was previously observed between proestrus and estrus. We have found that ERbeta mRNA and protein were displayed in high levels in the estrus and in low levels in the proestrous phase. By applying kainic acid (KA) to adult rats, we demonstrated that up-regulation of ERbeta mRNA and protein in hippocampal CA regions was vulnerable to KA-induced excitotoxicity. Furthermore, we note a concomitant decrease of ERbeta in the excitotoxicity-resistant denate gyrus that undergoes intense plastic changes, including synaptogenesis. These data suggested that decreases in ERbeta expression correlated with increase in synapse formation. This notion has been tested in vitro in hippocampal cultures, in which overexpression of ERbeta by means of gene transfection resulted in the lowering of the dendritic spine density that was elevated by estrogen. In summary, our results suggest that ERbeta inhibits synapse formation in hippocampal neurons.
authors.affiliation: Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Szymczak
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kalita
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.forename: Basia
authors.initials: B
authors.lastname: Mioduszewska
authors.forename: Alena
authors.initials: A
authors.lastname: Savonenko
authors.forename: Alicja
authors.initials: A
authors.lastname: Markowska
authors.forename: Istvan
authors.initials: I
authors.lastname: Merchenthaler
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
mesh_terms: D000818:Animals; D003712:Dendrites / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000502:physiology*; D030762:Estrous Cycle / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D007608:Kainic Acid / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D047629:Estrogen Receptor beta; D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D007608:Kainic Acid