Master of Science in Biological Sciences, Youngstown State University, 2017, Department of Biological Sciences and Chemistry

The pineal gland is a naturally calcifying endocrine organ which produces and releases the sleep-promoting hormone melatonin which also serves as an antioxidant. Fluoride is attracted to the calcium in the pineal gland and inhibits the synthesis and activity of melatonin, induces oxidative stress, and causes cellular changes to the neurons of the hippocampus. Morphological changes to the pineal gland have been demonstrated with increased age, exposure to light during a melatonin production period, or sleep deprivation. This study sought to examine the effects of fluoridated water on the morphology of the pineal gland. The effects of a fluoride-free flush were compared to fluoride treatment. Group 1, previously raised on fluoridated tap water served as a control that was sacrificed at the onset of the experiment. The remaining four groups were then subjected to a four-week fluoride-free diet with Group 2 being sacrificed at the end of this period. Group 3 was maintained on fluoride-free food and water while Groups 4 and 5 were switched to fluoridated water for the remaining four weeks. The fluoride-free flush resulted in an increase in the number of supporting cells and pinealocytes and a decrease in the nuclear diameter of pinealocytes, suggesting that the flush encouraged growth of the gland. Fluoride treatment had no effect on the number of supporting cells, but decreased the number of pinealocytes and their nuclear diameter, suggesting that fluoride is detrimental to the pineal gland.

Committee: Mark Womble PhD (Advisor); Jill Tall PhD (Committee Member); Jeffrey Coldren PhD (Committee Member) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 2017, Philosophy

One of the most defining features of Rene Descartes' philosophy is the nature and degree of his dualism. As conventional readings go, Descartes neatly divides reality into two radically distinct types of substances—mind and body—and never the two shall meet. I argue, however, that Descartes does not split the mind from body as cleanly as conventional readings might think, that the two metaphysical hemispheres are not entirely separate. There is a bridge linking the two together, and the road map for discovery is found in Descartes' theory of sensory perception. Descartes' views on sensory perception is the most apt topic in which to seek an understanding of the relationship between mind and body because, in general, it requires some explanation about how immaterial souls are informed by material bodies; that is, the topic demands that Descartes hypothesize about how perceptions—which he considers exclusive to minds—can be of things wholly distinct in kind, things that are essentially material. Throughout his writings, Descartes pays most attention to visual sensory perception, and so I follow in suit. Moreover, I concentrate on visual shape perception because, as I argue, understanding this aspect of Descartes' philosophy leads to insights about the precise relationship between mind and body. To give a feel for the overall shape of my reading, consider “veil of perception” interpretations of Descartes. Such readings understand Descartes as wedging a “third thing” between perceivers and the perceived object, standardly ascribing the “third thing” to the mind itself. On such readings of Descartes, sensory access to the physical world is mediated by mental images. So, according to these readings, one sees an idea of a tree, but not the tree itself. According to the reading of Descartes I offer, however, the veil is sheerer than previously thought. For I argue that the “third thing” bridging perceivers with the perceived belongs to bodily substance. In par (open full item for complete abstract)

Committee: Lisa Downing Ph.D. (Advisor); Julia Jorati Ph.D. (Committee Member); Lisa Shabel Ph.D. (Committee Member) Subjects: Philosophy; Philosophy of Science

Doctor of Philosophy, The Ohio State University, 1963, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1961, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Master of Science, Miami University, 2005, Zoology

Target-derived neurotrophic factors such as nerve growth factor (NGF) and neurotrophin-3 (NT-3) regulate sympathetic neuron survival. In the present study, NGF and NT-3 protein and transcript levels were examined in peripheral tissues in order to determine their role in neuronal atrophy observed in aging. The most obvious age-related alteration was a dramatic increase (up to 50-fold) in the proNGF species (25 kDa) in the superior cervical ganglion (SCG) and targets that atrophy in aging. In the iris, a tissue protected into old-age, proNGF was decreased. Alterations in NGF transcript generally paralleled changes in NGF protein, albeit to a lesser degree. Though NT-3 protein was significantly increased in SCG, only minor changes were observed in targets, even though NT-3 mRNA generally was decreased. In contrast, both NT-3 transcript and NT-3 precursors were increased in iris. The dramatic alterations in NGF precursor proteins and significant increases in NGF transcript, together with minimal changes in NT-3, indicate that altered NGF regulation, particularly the presence of proNGF, contributes to the degeneration of aged sympathetic neurons.

Committee: Lori Isaacson (Advisor) Subjects:

Doctor of Philosophy, Case Western Reserve University, 2012, Biology

This dissertation is composed of three major contributions focusing on the circadian and asymmetric properties of zebrafish. First we demonstrated that the gene expression rhythms could be established in the pineal organ of cyc mutant larvae lacking the Suprachiasmatic nucleus (SCN) structure. We also found that such rhythmic gene expression pattern could be maintained under constant environments. However, the amplitudes of the expression rhythms were decreasing by the end of the second day under constant environments. These findings indicate that the zebrafish SCN is not required for establishing the circadian rhythms of the pineal organ, but may be needed for maintaining the rhythms. These findings also further support the theory that unlike the highly centralized mammalian circadian system, circadian rhythms in zebrafish are decentralized [Chapter 2 and (Noche et al., 2011)]. We then demonstrated that when the neural tube failed to close and resulted in divided epithalamic structures, the left-right (L/R) asymmetric characteristics of the epithalamus become left-isomerized. Normally asymmetrically expressed Nodal pathway genes became bilaterally expressed on both sides of the divided pineal organ. Also, normally left-located parapineal organ were observed on both sides, and both habenula nuclei exhibited a “left” pattern of gene expression. In contrast, other aspects of pineal development, such as expression of photoreceptor, projection neuron, and circadian related genes, remained normal. These findings indicate that a closed neural tube is required for the establishing of epithalamus left-right asymmetry. Our results also imply a previously unknown short-ranged mechanism that prevents the target tissues from acquiring left characteristics during the epithalamus L/R asymmetry establishment (Chapter 3). We also contributed in characterizing a novel zebrafish mutation sec61al1c163, which was originally identified for affecting the habenular complex L/R asymmet (open full item for complete abstract)

Committee: Christopher A. Cullis PhD (Committee Chair); Jennifer O. Liang PhD (Committee Co-Chair); Radhika Atit PhD (Committee Member); Stephen E. Haynesworth PhD (Committee Member); Ronald Conlon PhD (Committee Member) Subjects: Developmental Biology

Doctor of Philosophy, Case Western Reserve University, 2008, Biology

The zebrafish pineal is a powerful system to dissect the regulation of circadian rhythms during development. It has all the elements of the circadian timing system. Under constant conditions, an endogenous pineal clock drives many rhythms including higher levels of circulating melatonin at night and lower levels during the day. Photoreceptors within the zebrafish pineal reset the endogenous circadian oscillator. It has been shown that light is partly required for higher levels of mRNA expression of two rhythmic pineal genes extra-ocular rhodopsin (exorh) and serotonin-N-acetyltransferase 2 (aanat2) that encodes for a putative photopigment and a major melatonin biosynthetic enzyme, respectively. Many candidate photopigments are expressed in the zebrafish pineal such as red opsin, blue opsin, and Exorh. To determine the role of Exorh protein, I used two non-overlapping antisense morpholino oligonucleotides (MOs) to deplete Exorh. I found a dramatic reduction in the levels of exorh mRNA in Exorh-deficient embryos. Together with my fellow graduate student Lain Pierce, I discovered significantly reduced levels of aanat2 mRNA in Exorh-deficient embryos. Since higher levels of exorh and aanat2 mRNAs are partly dependent on light, these results suggest that Exorh participates in a light-sensing pathway that ultimately causes the activation of pineal gene expression. This is the first evidence for Exorh function. In mammals, pineal rhythms are regulated by the suprachiasmatic nucleus (SCN) of the hypothalamus. While a similar structure has been identified in teleost fish such as zebrafish, evidence for its function is lacking. To define the role of the zebrafish SCN, I analyzed pineal gene expression rhythms in cyclops (cyc) mutants. cyc mutants are missing the ventral brain including the SCN precursors. My fellow graduate student Po-Nien Lu and I showed that the rhythmic expression patterns of aanat2 and exorh are indistinguishable between wild type (WT) fish and cyc mu (open full item for complete abstract)

Committee: Jennifer O. Liang Ph.D. (Advisor); Mark A. Willis Ph.D. (Committee Chair); Radhika P. Atit Ph.D. (Committee Member); Ron A. Conlon Ph.D. (Committee Member); Stephen E. Haynesworth Ph.D. (Committee Member); Neal S. Peachey Ph.D. (Committee Member) Subjects: Biology

Doctor of Philosophy, Case Western Reserve University, 2008, Genetics

Circadian rhythms are predictable oscillations in behavior such as the sleep wake cycle and biomolecular profiles such as rhythmic changes in gene transcription. These oscillations receive entraining cues from environmental inputs such as the light/dark photoperiod that regulate endogenous molecular clocks which in turn produce rhythmic outputs. The zebrafish pineal organ is an excellent model to study these molecular profiles because phototransducive molecules as well as the clock and its outputs are all housed within the same cells. Additionally, zebrafish embryos undergo rapid and external development such that the molecular pineal clock is functional in as little as 24 hours post fertilization. However, capturing embryonic samples at all time points in the circadian cycle can be challenging. Not only is the health of the researcher compromised when working odd hours but experimental results may be altered by handling samples at inappropriate times. To address this issue, I have led the research and design of a new technology. The Time Reaper 5-Channel Automatic Liquid Dispenser (TimeR) delivers up to 50 mL of paraformaldehyde to embryos in a Petri dish at preset times. In testing the TimeR I have shown that the pattern of expression for a number of genes is indistinguishable between embryos fixed manually versus remotely and that the TimeR is also suitable for fixing embryos for whole mount immunostaining. The TimeR was used frequently in securing data for the body of my dissertation work. The zebrafish opsin protein Exo-rhodopsin (Exorh) is expressed in pineal photoreceptors and is a candidate to mediate the effects of environmental light on pineal rhythms and melatonin synthesis. We demonstrate that Exorh has an important role in regulating gene transcription within the pineal. In developing embryos that lack Exorh, expression of the exorh gene itself and of the melatonin synthesis gene serotonin N-acetyl transferase 2 (aanat2) are significantly reduced. Th (open full item for complete abstract)

Committee: Jennifer Liang PhD (Advisor); Helen Salz PhD (Committee Chair); Peter Harte PhD (Committee Member); Mark Adams PhD (Committee Member); Heather Broihier PhD (Committee Member) Subjects: Genetics

Master of Science, University of Akron, 2007, Biology

During embryogenesis, tissue differentiation and organ development require cells expressing specific molecules that cue migration, aggregation and differentiation. One group of molecules involved in such processes is cadherin molecules, which are defined as calcium dependant adhesion molecules. This study is intended to investigate the role of cadherin-6 in the development of zebrafish pineal gland and retinal photoreceptors. Cadherin expression in the central nervous system (CNS) has been investigated in various vertebrate animals, but there is little information on cadherin function in retinal photoreceptor differentiation, and scarcer knowledge on cadherin function in the pineal gland development. My results showed that cadherin-6 affected retinal development more than the development of the pineal gland

Committee: Qin Liu (Advisor) Subjects: Biology, Animal Physiology