Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
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Item ACUTE EXERCISE INDUCED MICROSTRUCTURAL AND FUNCTIONAL CHANGES IN THE HIPPOCAMPUS OF OLDER ADULTS(2023) Callow, Daniel; Carson, Jerome J; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Declining memory function is a common complaint of aging adults and a primary symptom of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The hippocampus is often the first brain area to exhibit noticeable deficits in age and pathologically-related cognitive decline and is a necessary structure for proper memory function. More specifically, the dentate gyrus (DG) and the third cornu ammonis area (CA3) of the hippocampus directly support mnemonic discrimination (MD), which is the process of reducing interference among new representations and distinctly encoding them as independent memories. Poor MD is associated with age and is a presymptomatic biomarker of cognitive decline and is believed to result from reduced neurogenesis, angiogenesis, and synaptogenesis within the DG/CA3 subregion of the hippocampus. While causes and treatments for memory decline remain elusive, lifestyle interventions, especially physical activity, have received attention as cost-effective and safe means of ameliorating and potentially preventing cognitive decline in a growing aging population. Animal and human studies suggest exercise benefits the hippocampal structure, preserving neurogenesis and angiogenesis in aging rodents and macrostructure and memory in older adults. However, the mechanisms by which exercise affects the human hippocampus remains a significant knowledge gap in the field and is a critical aspect in understanding the long-term impact exercise has on the aging hippocampus. To better address this gap, researchers have begun implementing acute exercise studies, which allow for greater control of non-exercise-related factors, are cheaper and more time efficient to conduct than training studies, and can predict and inform training-related adaptations. Unfortunately, limitations in the study designs, population tested, specificity of cognitive tasks, and spatial resolution of human imaging techniques have posed significant barriers to our understanding of how acute exercise relates to healthy brain aging at the functional and microstructural levels. Therefore, the objective of this dissertation was to expand our understanding of how acute aerobic exercise alters the function and microstructure of the aging hippocampus. Three within-subject studies were conducted comparing the relationship between a 30-minute bout of moderate to vigorous intensity aerobic exercise vs seated rest on MD performance, hippocampal microstructure, and high-resolution hippocampal-subfield microstructure and functional activity in healthy older adults. In study one, acute exercise preserved MD performance compared to decrements exhibited after seated rest in a pre and post-condition study design. In study two, a post-condition-only study design, acute exercise elevated microstructural diffusion within the hippocampus, indicative of a hippocampal neuroinflammatory response and upregulation of neurotrophic factors. Finally, in study three, a post-condition-only study design, we found that acute exercise resulted in lower MD, suppressed MD-related DG/CA3 network hyperactivity (indicative of healthier network function), and led to higher DG/CA3 extracellular diffusion. However, these neuroimaging-based correlates of hippocampal neuroplasticity and network function were not associated with differences in MD performance. These findings suggest that higher-intensity acute exercise can alter memory performance and stimulate neuroplasticity and neurotrophic cascades within the hippocampus and the DG/CA3 subfield, potentially via different mechanisms. Furthermore these results give insight into the immediate neurotrophic and behavioral effects of acute moderate to vigorous intensity aerobic exercise in older adults and provide new methods and tools for better understanding if and how exercise promotes healthy brain aging. Finally, these initial findings lay a foundation for optimizing exercise prescription and identifying future effective exercise treatments.Item CHARACTERIZATION OF CHRONIC MONOCULAR DEPRIVATION AND ESTROGEN ADMINISTRATION IN ADULT RODENTS(2018) Sengupta, Deepali Clare; Quinlan, Elizabeth M; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Reduced synaptic plasticity and excitatory synapse density contribute to age-related cognitive decline, and constrain recovery of function from injury in adults. A parallel reduction in circulating sex hormones in both sexes, particularly estrogens, exacerbates this decline in synaptic plasticity. Conversely, estrogen therapy in aged members of many species restores synapse density, promotes synaptic plasticity, and improves learning/memory. Importantly, acute estrogen administration can promote rapid synaptogenesis, and these new synapses can be stabilized by activity. Here I ask if estrogen treatment can promote synaptic plasticity in the primary visual cortex (V1) of aged rats. I demonstrate robust expression of estrogen receptors (ERs) in V1 of adult male and female rats, suggesting an opportunity to enhance plasticity with estrogens. I test this hypothesis following the induction of amblyopia by chronic monocular deprivation (cMD). I show that cMD reduces thalamic innervation from the deprived eye, and increases molecular markers which constrain plasticity, consistent with observations that the deficits induced by cMD are highly resistant to reversal. Surprisingly, cMD did not change markers for excitatory synapses, suggesting a homeostatic increase in synapses serving the non-deprived eye (NDE) to maintain synaptic density within an optimal range. Importantly, visually-evoked potentials (VEPs) induced by repetitive visual stimulation to the deprived eye depress more rapidly than those of the NDE, consistent with cMD inducing an increase in the probability of neurotransmitter release (Pr) at synapses in the cMD pathway. In contrast, treatment of cMD adults with a single dose of 17α estradiol significantly increased markers for excitatory synapses, and estradiol treatment followed by visual stimulation also increased markers for excitatory synapse activity. Repetitive estradiol treatments increased excitatory synapse markers, but not synaptic activity markers. Furthermore, one dose of estradiol enhanced VEP amplitude following repetitive visual stimulation, however this was observed only in response to stimulation of the NDE. As presynaptic ERs are known to increase Pr at glutamatergic synapses, this suggests that the effects of estradiol are specific to spared synapses where Pr has not been up-regulated by deprivation. Exploiting this selectivity may allow for receptive field remapping of spared inputs around a scotoma or cortical infarctItem The Gonadotropin Releasing Hormone-3 System in Zebrafish: Early Development and Regulation(2008-12-15) Abraham, Eytan; Zohar, Yonathan; Marine-Estuarine-Environmental Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The objective of this study was to expand our understanding of the early development of forebrain Gonadotropin Releasing Hormone (GnRH) neurons in vertebrates in general and in fish in particular. The correct migration during early development of the hypophysiotropic GnRH neurons from the olfactory region to the hypothalamus is crucial for normal gonadal development and reproduction. We developed a Tg(GnRH3:EGFP) zebrafish line in which EGFP is specifically expressed in GnRH3 neurons. Using this line, we have studied in detail the early spatiotemporal development of the GnRH3 system in vivo. In addition, we have studied various factors, including GnRH3, Netrins and Hedgehog to better understand some of the mechanisms that mediate this complex axophilic neuron migration event. Lastly, we have conducted targeted GnRH3 neuron ablation experiments in view of determining the embryonic origin of POA-hypothalamic GnRH3 neurons and the effect of lack of GnRH3 neurons in the CNS. Our findings show that: 1) GnRH neurons first differentiate and express GnRH3 at 24-26 hours post fertilization (hpf) and immediately thereafter begin to extend fibers. 2) GnRH3 neurons project a complex network of fibers, prior the GnRH3 soma migration, to various CNS regions, and to the pituitary. 3) GnRH3 soma begin migrating towards the hypothalamus at 3 days post fertilization (dpf), passing through the terminal nerve (TN), lateral telencephalon, and reaching the hypothalamus by 12 dpf. 4) expression of GnRH3 itself is necessary for the normal early differentiation and fiber extensions of GnRH3 neurons. 5) Netrin1a is directly involved as a chemoattractant in GnRH3 fiber organization and subsequently, in GnRH3 soma migration to the hypothalamus. 6). Netrin2 is required for normal early ZF embryogenesis. 7). Sonic hedgehog a does not serve as a specific factor in the development of the GnRH3 system. 8). GnRH3 neuron regeneration capacity is temporally limited. 9). Successful ablation of olfactory GnRH3 neurons during development results in lack of GnRH3 neurons in the entire sexually mature brain as well as abnormal gonadal development and inability to reproduce. This study expands our understanding vis-à-vis the early events that occur during GnRH3 system development and that regulate this complex process. In a broader sense these findings augment current knowledge regarding the regulation of long range tangential neuron migration during development.