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Articles 1 - 10 of 10
Full-Text Articles in Life Sciences
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
Arts & Sciences Electronic Theses and Dissertations
Brain extracellular concentration of the peptide amyloid-β (Aβ) is a major contributor to Alzheimer’s disease (AD) pathogenesis. High Aβ levels in the extracellular space precipitate aggregation of the peptide into soluble and insoluble toxic species. This process begins decades before cognitive impairment and triggers the cascade of pathology that eventually leads to AD. Synaptic activity is key to the regulation of extracellular Aβ levels. Presynaptic activity drives the production of Aβ, while postsynaptic receptor activation exhibits more nuanced regulation. For example, high levels of NMDA receptor (NMDA-R) activation have been shown to decrease Aβ production through the extracellular signal-regulated kinase …
Longitudinal Cerebrospinal Fluid Biomarkers Of Alzheimer Disease: Movement Toward The Diagnosis, Prognosis And Staging Of Disease, Courtney Sutphen
Longitudinal Cerebrospinal Fluid Biomarkers Of Alzheimer Disease: Movement Toward The Diagnosis, Prognosis And Staging Of Disease, Courtney Sutphen
Arts & Sciences Electronic Theses and Dissertations
Alzheimer’s disease (AD) is a devastating neurodegenerative disease that slowly claims the memories and experiences that comprise the life experiences of individuals that suffer from the disease. Despite a continually accelerating pace of research and discovery, a viable therapeutic intervention for AD has yet to be realized. There are a multitude of factors that may contribute to this difficulty including the challenge of separating the overall disease of Alzheimer’s from the clinically recognizable memory loss that occurs in what is now known to be the end-stage of the disease. Efforts to treat AD have increasingly turned toward very early disease …
Bridging The Translational Gap Between Rodent And Human Pain Research, Tayler Diane Sheahan
Bridging The Translational Gap Between Rodent And Human Pain Research, Tayler Diane Sheahan
Arts & Sciences Electronic Theses and Dissertations
The treatment of chronic pain is an immense clinical and societal burden rooted in the ineffectiveness and adverse side effects of existing analgesics. Extensive efforts have been directed towards the development of novel pain therapies with maximal efficacy and minimal unwanted effects; however, putative therapeutic targets identified in preclinical rodent models rarely translate in clinical trials. The poor translational record of basic pain research findings has been attributed, in part, to the use of suboptimal rodent pain models and behavioral endpoints used to assess putative analgesics, as well as differences in the pharmacological profiles of rodents and humans. The work …
The Impact Of Delay On Retrieval Success In The Parietal Memory Network, Nathan Anderson
The Impact Of Delay On Retrieval Success In The Parietal Memory Network, Nathan Anderson
Arts & Sciences Electronic Theses and Dissertations
Recent work has identified a Parietal Memory Network (PMN), which exhibits regular patterns of activation during memory encoding and retrieval. Among these characteristic patterns, this network displays a strong “retrieval success” effect, showing greater activation for correctlyremembered studied items (hits) compared to correctly-rejected novel items (CRs). To date, most relevant studies have used short retention intervals. Here, we ask if the retrieval success effect seen in the PMN would remain consistent over a delay. Twenty participants underwent fMRI while encoding and recognizing scenes. Greater activity for hits than for correctly-rejected lures within PMN regions was observed after a short delay …
Neurogenetics Of The Externalizing Spectrum, Caitlin E. Carey
Neurogenetics Of The Externalizing Spectrum, Caitlin E. Carey
Arts & Sciences Electronic Theses and Dissertations
Externalizing spectrum disorders, which include attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, alcohol and substance use disorders, and antisocial personality disorder, are characterized by behavioral disinhibition and are thought to be manifestations of a common heritable liability factor throughout the lifespan. However, relatively little is known about their underlying etiology. Here, I probe genetic and neural risk mechanisms for externalizing psychopathology in three complementary studies. First, I report an indirect association between genetic risk for childhood attention-deficit/hyperactivity disorder (ADHD) and problem drinking in young adulthood, mediated by heightened reward-related neural activity within the ventral striatum, among 404 college students. I …
Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy
Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy
Arts & Sciences Electronic Theses and Dissertations
The seemingly limitless capacities of mammals to sense, respond, and manipulate their environments stems from their structurally and functionally diverse nervous systems. Establishing these complex behaviors requires the integration of many biological phenomena including, morphogenetic gradients, cell-cell signaling, transcriptional networks, cell migration and epigenetic gene regulation. As mammalian development progresses, these pathways coordinate the production of highly specialized neuronal and glial cells, that connect and communicate with another in an even more complex manner. While evolution has shaped a multitude of pathways to produce numerous favorable traits, it has also created an intricate system vulnerable to disease. The loss of …
The Role Of Vip Scn Neurons In Circadian Physiology And Behavior, Cristina Mazuski
The Role Of Vip Scn Neurons In Circadian Physiology And Behavior, Cristina Mazuski
Arts & Sciences Electronic Theses and Dissertations
Located in the ventral hypothalamus, the suprachiasmatic nucleus (SCN) is necessary for entraining daily rhythms in physiology and behavior to environmental cues. Though the 20,000 neurons of the SCN uniformly express GABA, they differ greatly in neuropeptide content. One anatomically and functionally distinct class of neuropeptidergic SCN neurons is vasoactive intestinal polypeptide (VIP). Expressed by approximately 10% of SCN neurons, VIP is necessary for synchronizing single-cell SCN rhythms to produce coherent output and sufficient for entrainment. However, little is known about the firing activity of these neurons releases VIP and results in circadian entrainment. We utilized multielectrode array technology and …
Genetic And Genomic Dissections Of Myelinating Glial Cell Development, Breanne Leigh Harty
Genetic And Genomic Dissections Of Myelinating Glial Cell Development, Breanne Leigh Harty
Arts & Sciences Electronic Theses and Dissertations
Myelin is a multilamellar sheath made by specialized glial cells that iteratively spiral and compact their plasma membranes around axon segments. In vertebrate nervous systems, myelination facilitates rapid action propagation and provides trophic support critical for neuronal survival. In the central nervous system (CNS), oligodendrocytes (OLs) extend many processes to simultaneously ensheath multiple axons, while in the peripheral nervous system (PNS), myelinating Schwann cells (SCs) pair 1:1 with a single axon segment. Elaboration of the myelin sheath is one of the most exquisite and complex examples of massive coordinated cellular shape changes in the vertebrate nervous system. Furthermore, the importance …
Functional Brain Organization In Space And Time, Timothy Laumann
Functional Brain Organization In Space And Time, Timothy Laumann
Arts & Sciences Electronic Theses and Dissertations
The brain is a network functionally organized at many spatial and temporal scales. To understand how the brain processes information, controls behavior and dynamically adapts to an ever-changing environment, it is critical to have a comprehensive description of the constituent elements of this network and how relationships between these elements may change over time. Decades of lesion studies, anatomical tract-tracing, and electrophysiological recording have given insight into this functional organization. Recently, however, resting state functional magnetic resonance imaging (fMRI) has emerged as a powerful tool for whole-brain non-invasive measurement of spontaneous neural activity in humans, giving ready access to macroscopic …
Tissue Damage Quantification In Alzheimer's Disease Brain Via Magnetic Resonance Gradient Echo Plural Contrast Imaging (Gepci), Yue Zhao
Arts & Sciences Electronic Theses and Dissertations
Alzheimer’s disease (AD) affected approximately 48 million people worldwide in 2015. Its devastating consequences have stimulated an intense search for AD prevention and treatment. Clinically, AD is characterized by memory deficits and progressive cognitive impairment, leading to dementia. Over the past two to three decades, researchers have found that amyloidbeta (Aβ) plaques and neurofibrillary tau tangles occur during a long pre-symptomatic period (preclinical stage) before the onset of clinical symptoms. As a result, identification of the preclinical stage is essential for the initiation of prevention trials in asymptomatic individuals. Currently, Positron Emission Tomography (PET) imaging with injected 11C or 18F …