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dc.contributor.advisorZoran, Mark J.en_US
dc.creatorCox, Kimberly Yvonneen_US
dc.date.accessioned2010-01-15T00:10:52Zen_US
dc.date.accessioned2010-01-16T00:32:56Z
dc.date.available2010-01-15T00:10:52Zen_US
dc.date.available2010-01-16T00:32:56Z
dc.date.created2007-12en_US
dc.date.issued2009-05-15en_US
dc.identifier.urihttp://hdl.handle.net/1969.1/ETD-TAMU-2436
dc.description.abstractThe mammalian brain contains a regulatory center in the diencephalic region known as the hypothalamus that plays a critical role in physiological homeostasis, and contains a variety of centers for behavioral drives, such as hunger and thirst. Located deep within the hypothalamus is the suprachiasmatic nucleus (SCN), or the master biological clock, that organizes rhythmic physiology and behavior, such that critical events take place at the most appropriate time of the day or night and in the most appropriate temporal, phase relationships. Cell-to-cell communication is essential for conveying inputs to and outputs from the SCN. The goal of the present study was to use an immortalized neural cell line (SCN2.2), derived from the presumptive anlage of the rat suprachiasmatic nucleus, as an in vitro model system to study intercellular communication among SCN cells. I tested whether the pineal neurohormone melatonin could modulate cell-to-cell signaling, via both dye coupling (gap junctional communication) and calcium waves (ATP-dependent gliotransmission). I also tested whether extracellular ATP could influence the spread of calcium waves in SCN2.2 cells. Lastly, the ability of extracellular ATP to modulate SCN physiological responses to melatonin in SCN2.2 cells was examined. I show that melatonin at a physiological concentration (nM) reduced dye coupling (gap junctional communication) in SCN2.2 cells, as determined by a scrape loading procedure employing the fluorescent dye lucifer yellow. Melatonin caused a significant reduction in the spread of calcium waves in cycling SCN2.2 cultures as determined by ratiometric calcium imaging with Fura-2 AM, a calcium sensitive indicator dye. This reduction was greatest when an endogenous circadian rhythm in extracellular ATP accumulation, determined by luciferase assay, was at its trough or lowest extracellular concentration. In addition, melatonin and ATP interacted in the regulation of gliotransmission (calcium waves), and this interaction was also specific to particular phases of the endogenous SCN physiological rhythmicity. Thus, I have established that a complex interaction exists between established melatonin signaling pathways and this newly discovered ATP accumulation rhythm, with the mechanisms underlying this relationship linked to endogenous cycling of SCN cellular physiology.en_US
dc.format.mediumelectronicen_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.subjectSuprachiasmatic Nucleusen_US
dc.subjectMelatoninen_US
dc.subjectATPen_US
dc.subjectGliotransmissionen_US
dc.subjectCalcium Wavesen_US
dc.titleMelatonin modulates intercellular communication among immortalized rat suprachiasmatic nucleus cellsen_US
dc.typeBooken
dc.typeThesisen
thesis.degree.departmentBiologyen_US
thesis.degree.disciplineBiologyen_US
thesis.degree.grantorTexas A&M Universityen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelMastersen_US
dc.contributor.committeeMemberBurghardt, Robert C.en_US
dc.contributor.committeeMemberEarnest, David J.en_US
dc.type.genreElectronic Thesisen_US
dc.type.materialtexten_US
dc.format.digitalOriginborn digitalen_US


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