%0 Journal Article %T Increasing Hippocampal Estrogen Receptor Alpha Levels via Viral Vectors Increases MAP Kinase Activation and Enhances Memory in Aging Rats in the Absence of Ovarian Estrogens %A Christine F. Witty %A Thomas C. Foster %A Susan L. Semple-Rowland %A Jill M. Daniel %J PLOS ONE %D 2012 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0051385 %X We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ER¦Á) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life estradiol treatment. These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ER¦Á in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ER¦Á (lenti-ER¦Á) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ER¦Á, the ER¦Á-regulated protein choline acetyltransferase, and phosphorylation of the ER¦Á-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ER¦Á to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ER¦Á delivery significantly increased levels of ER¦Á and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ER¦Á in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0051385