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Katarina Coulson Masters Thesis.pdf (844.8 KB)

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Exploring the Neural-Tumor Synapse: The Effects of Serotonin on C6 Glioma Cells

Coulson, Katarina Michelle
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1499012303669511

Abstract Details

2017, Master of Science (MS), Bowling Green State University, Biological Sciences.
Circadian rhythms influence tumorigenesis and the rate of tumor growth. A fundamental question is whether the circadian timing system alters cancer cell properties through neurosecretion at a neural-tumor synapse (NTS). The master clock of the circadian system is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and regulates multiple circadian rhythms in behavior and physiology including rhythms in neurotransmitter secretion in the brain. Like cells throughout the body, many cancer cell types also contain a circadian clock. The clock can modulate responsiveness of cancer cells to chemotherapeutic treatments. The question addressed in this study was whether glioma cancer cells show evidence of a circadian rhythm in their response to serotonin (5-HT), a neurotransmitter that could provide signaling of timing information through the NTS. This potential control of gliomas by the circadian clock might be used clinically to improve the timing and effectiveness of anticancer treatments. A dose-response curve was created to find an optimal dosage of 5-HT for further testing. This dosage (10 µM) significantly suppressed area and width of C6 rat glioma cells while also increasing cell circularity, resulting in a morphology resembling cells that are more invasive and motile following an epithelial-to-mesenchymal transition (EMT). A second neurotransmitter, glutamate, produced an opposite effect on area with increasing dosage. The optimized 5-HT treatment was then given to C6 cells at four-hour intervals for 48 hours to determine whether there are circadian effects of 5-HT on cell morphology. Before treatment, circadian clocks within the cells were synchronized using forskolin. The suppression of average cell area and width by 5-HT showed a circadian rhythm with a peak responsiveness just before the minimum of the previously described daily rhythm in 5-HT levels of rat brain. Treatments with 5-HT also caused a slowing of ongoing oscillations in intracellular Ca2+ of C6 cells, suggesting a possible mechanism through which a 5-HT NTS might function in altering gliomas. These results provide a potential drug target for suppressing EMT or controlling cell proliferation in gliomas by delivering serotonergic agents or related treatments at a time of day when cancer cells are most responsive
Michael Geusz, Dr. (Advisor)
Verner Bingman, Dr. (Committee Member)
Robert Huber, Dr. (Committee Member)
48 p.
Biology; Cellular Biology; Experiments; Health Sciences; Molecular Biology; Morphology; Neurobiology; Neurosciences; Oncology
neural-tumor synapse; serotonin; 5-HT; circadian rhythms; epithelial-to-mesenchymal transition; EMT; C6; glioma; cell morphology; serotonin circadian rhythm; serotonin dose response

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Citations

  • Coulson, K. M. (2017). Exploring the Neural-Tumor Synapse: The Effects of Serotonin on C6 Glioma Cells [Master's thesis, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1499012303669511

    APA Style (7th edition)

  • Coulson, Katarina. Exploring the Neural-Tumor Synapse: The Effects of Serotonin on C6 Glioma Cells. 2017. Bowling Green State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1499012303669511.

    MLA Style (8th edition)

  • Coulson, Katarina. "Exploring the Neural-Tumor Synapse: The Effects of Serotonin on C6 Glioma Cells." Master's thesis, Bowling Green State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1499012303669511

    Chicago Manual of Style (17th edition)

bgsu1499012303669511
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This open access ETD is published by Bowling Green State University and OhioLINK.