Life Sciences Commons^™

Role Of Calcium And Nitric Oxide Synthase (Nos) In Brain Mitochondrial Dysfunction, Vidya Nag Nukala

Theses and Dissertations--Neuroscience

Mitochondria are essential for promoting cell survival and growth through aerobic metabolism and energy production. Mitochondrial function is typically analyzed using mitochondria freshly isolated from tissues and cells because they yield tightly coupled mitochondria, whereas those from frozen tissue can consist of broken mitochondria and membrane fragments. A method, utilizing a well-characterized cryoprotectant such as dimethyl sulfoxide (DMSO), is described. Such mitochondria show preserved structure and function that presents us with a possible strategy to considerably expand the time-frame and the range of biochemical, molecular and metabolic studies that can be performed without the constraints of mitochondrial longevity ex vivo …

Ambystoma: Perspectives On Adaptation And The Evolution Of Vertebrate Genomes, Jeramiah James Smith

University of Kentucky Doctoral Dissertations

Tiger salamanders, and especially the Mexican axolotl (Ambystoma mexicanum), are important model organisms in biological research. This dissertation describes new genomic resources and scientific results that greatly extend the utility of tiger salamanders. With respect to new resources, this dissertation describes the development of expressed sequence tags and assembled contigs, a comparative genome map, a web-portal that makes genomic information freely available to the scientific community, and a computer program that compares structure features of organism genomes. With respect to new scientific results, this dissertation describes a quantitative trait locus that is associated with ecologically and evolutionarily relevant …

Xenobiotic Transporters In Lactating Mammary Epithelial Cells: Predictions For Drug Accumulation In Breast Milk, Philip Earle Empey

Theses and Dissertations--Pharmacy

Recent literature has established that breast cancer resistance protein (ABCG2) is upregulated during lactation and is responsible for the greater than predicted accumulation of many drugs in breast milk. The objectives of this project were (1) to investigate the role of this transporter in the reported apically-directed nitrofurantoin flux in the CIT3 cell culture model of lactation, (2) to develop a mathematical model for drug transfer into breast milk to relate initial flux rates, steady-state concentrations, efflux ratios, and in vivo milk to serum ratios (M/S) and (3) to identify xenobiotic transporters that are highly expressed, and therefore potentially important …

Functional Properties Of L-Glutamate Regulation In Anesthetized And Freely Moving Mice, Kevin N. Hascup

Theses and Dissertations--Neuroscience

L-glutamate (Glu) is the predominant excitatory neurotransmitter in the mammalian central nervous system with involvement encompassing learning and memory, cognition, plasticity, and motor movement. Dysregulation of the glutamatergic system is implicated in several neurological disorders including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis. The mechanisms underlying these neurological disorders are not clear, but evidence suggests that abnormal Glu neurotransmission plays a role. Elevated levels of Glu in the synaptic cleft overstimulate the N-methyl-Daspartate receptor leading to excitotoxicity, which causes neuronal loss in chronic neurological diseases. What is less understood is the source for the elevated Glu levels. …

The Role Of Macrophages In Olfactory Neurogenesis, Aaron S. Borders

Theses and Dissertations--Physiology

Olfactory sensory neurons (OSNs) undergo continual degeneration and replacement throughout life, a cycle that can be synchronized experimentally by performing olfactory bulbectomy (OBX). OBX induces apoptosis of mature OSNs, which is followed by an increase in the proliferation of progenitor basal cells. Macrophages, functionally diverse immune effector cells, phagocytose the apoptotic OSNs and regulate the proliferation of basal cells. This provides an advantageous environment to study how macrophages regulate neuronal death, proliferation, and replacement.

The purpose of this dissertation was to identify the cellular and molecular mechanisms by which macrophages regulate the degeneration/proliferation cycle of OSNs. Macrophages were selectively depleted …