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
| Autor: | Jill M. Daniel, Christine F. Witty, Thomas C. Foster, Susan L. Semple-Rowland |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Aging lcsh:Medicine Hippocampal formation Hippocampus Behavioral Neuroscience Learning and Memory 0302 clinical medicine Hippocampus (mythology) lcsh:Science 0303 health sciences Multidisciplinary Kinase Obstetrics and Gynecology Neurochemistry Animal Models Choline acetyltransferase Ovariectomized rat Medicine Mitogen-Activated Protein Kinases Menopause Research Article medicine.medical_specialty Ovariectomy Genetic Vectors Biology Signaling Pathways 03 medical and health sciences Model Organisms Memory Internal medicine medicine Animals Maze Learning Protein kinase B 030304 developmental biology lcsh:R Estrogen Receptor alpha Neuroendocrinology Animal Cognition Rats Neuroanatomy Endocrinology Rat lcsh:Q Molecular Neuroscience Estrogen receptor alpha 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE, Vol 7, Iss 12, p e51385 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) 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 ERα 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 ERα (lenti-ERα) 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 ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα 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-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα 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. |
| Databáze: | OpenAIRE |
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