Peter Koulen2019-08-222019-08-222008-05-012014-02-24https://hdl.handle.net/20.500.12503/29152Sandra Longoria., Oxidative Stress Alters IP3 Receptor Function in the Neuronal Cell Line HT22, Master of Science (Biomedical Sciences), May 2008, 72 pp., 25 Figures. Oxidative stress contributes to the genesis of several neurodegenerative disorders such as Alzheimer’s Disease (AD). Oxidants such as, tert-butyl hydrogen peroxide (tBHP), have been used in in vitro models of neurodegeneration to induce oxidative stress. Small changes in the regulation of the intracellular calcium (Ca2+) concentration can contribute to brain aging and increase vulnerability of neurons to cellular and functional damage in neurodegenerative diseases. In neurons, inositol 1, 4, 5-trisphosphate (IP3) is a second messenger that is generated through receptor activity at the plasma membrane. IP3 receptors (IP3R) are located on endoplasmic reticulum (ER) membranes and are intracellular calcium channels (ICC) that release Ca2+ into the cytoplasm in response to activation by their ligand IP3. The goal of the present study was to measure the contribution of ICCs to Ca2+ dysregulation in neurons experiencing oxidative stress. I tested the hypothesis that oxidative stress induced with tBHP causes increased intracellular Ca2+ release via activation of IP3 receptors. I used the murine hippocampal cell line HT22, as a model for neuronal oxidative stress. Immunocytochemistry and Ca2+ imaging experiments were performed to identify areas of altered IP3R expression and activity under normal conditions and induced oxidative stress. tBHP treatment increased expression and Ca2+ release activity of neuronal IP3 receptors. My findings support that oxidative stress as seen in a number of neurodegenerative diseases negatively affects regulation of Ca2+ release through increased expression and activity of IP3 receptors.application/pdfenCell and Developmental BiologyCell BiologyCellsCellular and Molecular PhysiologyLife SciencesMedical Cell BiologyMedicine and Health SciencesMolecular and Cellular NeuroscienceNeuroscience and NeurobiologyNeurosciencesOther Cell and Developmental BiologyOxidative stressIP3 Receptor Functionneuronal cell line HT22Alzheimer’s Diseaseneurodegenerative diseasesintracellular calcium channelsCa2+neuronstBHPtert-butyl hydrogen peroxideThesis