Browsing by Subject "hippocampal neurons"
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Item Effect of Progesterone on Calcium Signaling of Hippocampal Neurons(2006-05-01) Hwang, Ji-Yeon; Koulen; Singh, Meharvan; Yang, ShaohuaJi-yeon Hwang, Effects of Progesterone on Calcium Signaling of Hippocampal Neurons. Master of Science (Pharmacology and Neuroscience), May 2006, 74 pp., 18 Figures. Progesterone (P4) is one of the steroid hormones responsible for female sexual behavior. It has been recently show that P4 plays also multiple roles in the central nervous system (CNS) including neuroprotection. Calcium (Ca2+) is involved in numerous cellular processes in nerve cells such as neurotransmitter release and cell death. In the present studies, we present evidence that P4 increases the activity of IP3R-mediated Ca2+ release within nerve cells leading to cell survival and neuroprotection. The purpose of the present study is to identify the subcellular distribution of all IP3Rs and other signaling proteins including Akt and phosphor-Akt, in the primary hippocampal neuron and to test the hypothesis that P4 controls the gain of IP3R-mediated intracellular Ca2+ signaling in neurons. We observed that primary hippocampal neurons express predominantly IP3R type 1, 2, and 3. The cellular distribution of all IP3R isoforms as well as Akt and phospho-Akt was increased in primary hippocampal neurons by P4 treatment. In addition, phospho-Akt was translocated to nucleus in response to P4. P4-pretreated neurons showed potentiated IP3R-mediated intracellular Ca2+ responses. Acute application of P4 resulted in transient elevations of intracellular Ca2+ concentrations. Our results will contribute to establishing potential pharmacological approaches for the treatment of pathological conditions characterized by a dysregulation of cellular Ca2+ concentrations such as Alzheimer’s disease.Item Translational Control by Estrogen-Induced Signaling in Primary Rat Hippocampal Neurons(2008-07-01) Smith, Lonell T.; Simpkins, James; Das, Hriday K.; Machu, Tina K.Smith, 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).