Texas A&M University at College Station
Permanent URI for this collectionhttps://hdl.handle.net/2249.1/23606
Texas A&M University is a land-grant, sea-grant and space-grant institution located in College Station, Texas. The university’s enrollment includes approximately 44,000 students studying for degrees in 10 academic colleges. This collection contains the theses and dissertations produced at A&M since 2002.
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Browsing Texas A&M University at College Station by Author "Abbott, Louise C"
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Item Analysis of Hippocampal Cell Proliferation, Survival, and Neuronal Morphology in P/Q-Type Voltage-Gated Calcium Channel Mutant Mice(2013-01-16) Nigussie, FikruTottering and leaner mutant mice carry mutations in the pore-forming subunit (?1A) of P/Q-type (CaV 2.1) voltage-gated calcium ion (Ca2+) channels that result in reduced Ca2+ current density. Since Ca2+ influx via voltage-dependent Ca2+ channels regulates important Ca2+-dependent neuronal processes including neurotransmitter release and synaptogenesis, we assessed effects of these mutations on hippocampus volume, neuronal density, neuronal morphology of hippocampal pyramidal cells in adult (six-month-old) mice, and adult neurogenesis in three-week-old and six-month-old mice. Hippocampal volume and neuronal density were assessed using hematoxylin and eosin stained serial sections. Neuronal morphology was assessed using Golgi-Cox staining as well as ultrastructural assessment using transmission electron microscopy. Adult hippocampal neurogenesis was assessed using standard 5-bromo-2?-deoxyuridine (BrdU) labeling with fluorescent immunohistochemistry (IHC) and proliferating cell nuclear antigen (PCNA) with diaminobenzidine IHC. To determine neuron and astrocyte survival, we used fluorescent double labeling for neurons with BrdU-neuronal nuclei IHC or astrocytes using BrdU-glial fibrillary acidic protein, respectively. Fluoro-Jade histochemistry was used to assess numbers of degenerating cells in the dentate gyrus subgranular zone. Decreased hippocampus volume was observed in tottering female mice and increased dentate hilar and CA1 cell density in mutant mice compared to wild type mice. Cell proliferation was increased in the hilus and combined CA3, CA2 and CA1 regions of mutant mice compared to wild type mice. Decreased total dendritic length and decreased number of dendritic intersections was observed in tottering mice compared to wild type mice. The decrease in dendritic arborization of tottering mice occurred at the concentric circles close to the neuronal cell body indicating that basal dendrites of CA1 pyramidal neurons are reduced. Taken together, P/Q-type voltage gated calcium channel mutation has age variable influence on adult hippocampal cell proliferation, and it altered neuronal morphology in terms of dendritic complexity in tottering mice, while the leaner mutation reduced mitochondrial density.Item Cerebellar Purkinje cell death in the P/Q -type voltage-gated calcium ion channel mutant mouse, leaner(Texas A&M University, 2006-04-12) Frank-Cannon, Tamy CatherineMutations of the ??1A subunit of P/Q-type voltage-gated calcium channels are responsible for several inherited disorders affecting humans, including familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6. These disorders include phenotypes such as a progressive cerebellar atrophy and ataxia. The leaner mouse also carries a mutation in the alpha(1A) subunit of P/Q-type voltage-gated calcium channels, which results in a severe cerebellar atrophy and ataxia. The leaner mutation causes reduced calcium ion influx upon activation of P/Q-type voltage-gated calcium channels. This disrupts calcium homeostasis and leads to a loss of cerebellar neurons, including cerebellar Purkinje cells. Because of its similarities with human P/Qtype voltage-gated calcium channel mutations, leaner mouse has served as a model for these disorders to aid our understanding of calcium channel function and neurodegeneration associated with calcium channel dysfunction. The aims of this dissertation were: (1) to precisely define the timing and spatial pattern of leaner Purkinje cell death and (2) to assess the role of caspases and specifically of caspase 3 in directing leaner Purkinje cell death. We used the mechanism independent marker for cell death Fluoro-Jade and demonstrated the leaner Purkinje cell death begins around postnatal day 25 and peaks at postnatal day 40 to 50. Based on this temporal pattern of Purkinje cell death we then investigated the role of caspases in leaner Purkinje cell death. These studies showed that caspase 3 is specifically activated in dying leaner cerebellar Purkinje cells. In addition, in vitro inhibition of caspase 3 activity partially rescued leaner Purkinje cells. Further investigation revealed that caspase 3 activation may be working together with or in response to macroautophagy. This study also indicated a potential role for mitochondrial signaling, demonstrated by the loss of mitochondrial membrane potential in leaner cerebellar Purkinje cells. However, our study revealed that if the loss of mitochondrial membrane potential is associated with leaner Purkinje cell death, this process is not mediated by the mitochondrial protein cytochrome C.Item Effect of Methylmercury Exposure on Heart and Skeletal Muscle Development in Zebrafish Embryos (Danio Rerio)(2014-09-04) Aguilar, SonnyMercury (Hg) in its elemental form is not effectively absorbed into the body until a methyl group is bound to an atom of Hg, creating methylmercury. Methylmercury (MeHg) is then readily absorbed from the digestive tract, and has demonstrated neurotoxic effects in both the developing and mature central nervous system (CNS). Previous studies have shown that exposure to high concentrations of MeHg results in both high morbidity and mortality rates demonstrated by cases of exposure I n the Faroe Islands, Japan and Iraq. Common symptoms exhibited after high exposure to MeHg included sensory disturbances in adults, while children demonstrate anatomical abnormalities and cognitive defects. Recent zebrafish studies have demonstrated decreased hatching rate, movement, and length along with abnormal/disorganized skeletal muscle, and heart related problems. To better understand the neurotoxic mechanisms of MeHg on zebrafish development, we investigated overall embryo growth, various aspects of heart development, and neuromuscular junction (NMJ) development. Using zebrafish embryos (ZFEs) as an animal model this study revealed that MeHg exposure for 24 hours had an effect on ZFEs , resulting in decreased heart rate, body length, elicited movement and spontaneous movement, including the number of times ZFEs spontaneously moved during the assessment time of one minute. MeHg exposure in ZFEs had no significant effect on mortality rate, hatching rate, yolk sac area, heart volume ventricle thickness, and pericardial cavity volume, as well as clustering of acetylcholine receptors (AChRs) and presynaptic vesicle aggregates at the NMJ. This study has confirmed previous reports in the literature that MeHg exposure has adverse effects on the general development of ZFEs. MeHg exposure also had adverse effects on heart development as well as skeletal muscle development, which adversely effected movement. Exposure to 24 hours of low concentrations of MeHg is likely to result in functional deficits that are not reflected in obvious morphologic deficits.Item Neurotoxic mechanisms of methylmercury: cellular and behavior changes(Texas A&M University, 2007-04-25) Bellum, SairamThe organic or methylated form of mercury (Hg), consisting of one methyl group bound to each atom of Hg, (methylmercury; MeHg), accounts for most of the Hg to which humans are exposed. MeHg, by virtue of its lipophilicity is highly neurotoxic to both the developing and mature central nervous system (CNS). Historically, MeHg has been implicated in high morbidity and mortality rates over the last 40 years in Japan, Iraq, Pakistan and Guatemala. The most common symptom exhibited in these exposure episodes was cerebellar ataxia. Recent in vitro studies using cultured granule cells showed that MeHg alters intracellular calcium ion ([Ca2+]i) homeostasis, potentiates reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential leading to apoptotic death of cerebellar granule neurons. To better understand the neurotoxic mechanisms of MeHg on cerebellum, changes with respect to biochemical processes in cerebellar granule cells and associated behavior changes were investigated. The aims of this dissertation were: (1) to assess mercury concentrations in mouse brain using different routes of administration and different tissue preparations, (2) to determine the behavior effects of in vivo MeHg exposure in young adult mice. (3) to understand specific biochemical processes leading to granule cell death/dysfunction due to in vivo MeHg toxicity in mice, and (4) to determine the toxic effects of in vivo MeHg exposure on mice aged between 16-20 months. The present results showed that repeated oral exposure to MeHg results in greater accumulation of Hg in brain tissue when compared to single oral or subcutaneous exposures at the same concentration of MeHg. Behavior analysis revealed that MeHg at the concentrations used in this study had profound effects on motor coordination and balance in young adult and aged mice. Investigation of biochemical processes in cerebellar granule cells of mice exposed to MeHg showed an increase in ROS generation, alteration of ([Ca2+]i (in young adult mice) and loss of MMP in young adult and aged mice. However, these changes did not lead to apoptotic cell death of granule cells at the concentrations of MeHg used and at the specific time point it was investigated in young adult mice.