Translational Control by Estrogen-Induced Signaling in Primary Rat Hippocampal Neurons

dc.contributor.advisorSimpkins, James
dc.contributor.committeeMemberDas, Hriday K.
dc.contributor.committeeMemberMachu, Tina K.
dc.creatorSmith, Lonell T.
dc.description.abstractSmith, Lonell T., Estrogen-Induced Signaling in Primary Rat Hippocampal Neurons. Masters (Biomedical Sciences). July 2008. 53 pages, 1 illustration, 7 figures. 37 titles. Abstract. The enhancing effects of 17-beta estradiol (E2) on performing cognitive tasks has been well demonstrated in laboratory mice, rats, and primates. Also there is ample clinical evidence indicating E2 enhances memory and reduces risk for Alzheimer’s disease. Furthermore, by increasing the capacity for long-term potentiation (LTP) in the hippocampus, E2 effectively increases the synaptic plasticity of this brain region in a manner that correlates with memory formation. The molecular mechanisms underlying LTP and synaptic plasticity have largely focused on the role of E2-induced signal transduction in the nucleus, and regulation of plasticity related gene expression at the transcriptional level. Conversely, the idea that E2-incuded signaling regulates at the level of translation and may play a role in these processes has yet to be explored. Recently, extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways have been shown to couple synaptic activation to protein synthesis machinery. Here we investigate translational control by E2-induced ERK and mTOR signaling in primary neuronal culture. E2-induced signaling resulted in enhanced phosphorylation of ribosomal protein (S6) and eIF4E binding protein 1 (4EBP1) in an ERK and mTOR-dependent manner. Neuronal activity-dependent ERK and mTOR signaling have been shown to induce translation of a diverse array of dendritic resident mRNAs, including α-CaMKII and GluR1 subunits. Using a green fluorescent protein (GFP) translational reporter, we demonstrated that E2 stimulates GFP protein synthesis. We have also demonstrated that E2 treatment of hippocampal neurons increases surface expression of GluR1. Taken together, our results provide a mechanism by which E2 modulates the components necessary for persistent forms of LTP and long-term depression (LTD).
dc.subjectBehavioral Neurobiology
dc.subjectBehavior and Behavior Mechanisms
dc.subjectCell and Developmental Biology
dc.subjectCognitive Neuroscience
dc.subjectLife Sciences
dc.subjectMedical Neurobiology
dc.subjectMedicine and Health Sciences
dc.subjectMolecular and Cellular Neuroscience
dc.subjectNervous System
dc.subjectNervous System Diseases
dc.subjectNeuroscience and Neurobiology
dc.subjectOther Neuroscience and Neurobiology
dc.subjectPsychiatry and Psychology
dc.subjectsignaling pathways
dc.subjectprimary rat
dc.subjecthippocampal neurons
dc.subject17-beta estradiol
dc.subjectcognitive tasks
dc.subjectAlzheimer’s disease
dc.subjectclinical evidence
dc.subjectgreen fluorescent protein
dc.subjecttranslational reporter
dc.subjectlong-term depression
dc.titleTranslational Control by Estrogen-Induced Signaling in Primary Rat Hippocampal Neurons
dc.type.materialtext School of Biomedical Sciences Sciences of North Texas Health Science Center at Fort Worth of Science


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