Medicine and Health Sciences Commons^™

Circulating Autoantibodies In Human Traumatic Spinal Cord Injury Subjects And Their Relationship To The Development Of Neuropathic Pain, Georgene Hergenroeder

Dissertations & Theses (Open Access)

Background:

Approximately 17,500 spinal cord injuries (SCI) occur yearly in the U.S. causing considerable morbidity and mortality. Neuropathic pain (NP) ensues in 40-70% of SCI. An autoimmune response resulting from disruption of the blood-spinal cord-barrier may be a contributor to NP. However, the relationship between autoantibodies and NP after SCI in humans has not been thoroughly characterized nor have autoantigens been identified. Glial fibrillary acidic protein (GFAP) and collapsin response mediator protein2 (CRMP2) were identified as candidate autoantigens. The hypothesis is that proteins from the injured spinal cord released by SCI trigger autoantibody production which can lead to the development …

Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes

Dissertations & Theses (Open Access)

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on …

Characterization And Reversal Of Doxorubicin-Mediated Changes In Sensory Neurons, Brittany L. Coughlin

Dissertations & Theses (Open Access)

Chemotherapeutic agents impair memory in humans as well as in animal models. Such memory impairments can be persistent, lasting years after exposure to chemotherapy. Doxorubicin (DOX), a common chemotherapeutic agent, has been associated with memory impairments in humans and induces memory deficits in rodent models. DOX also impairs serotonin (5-HT)-induced long-term synaptic facilitation (LTF) in Aplysia sensorimotor co-cultures, a cellular analog of long-term memory formation. In addition, DOX leads to dynamic activation of extracellular signal-regulated kinase (ERK), consisting of an immediate and a delayed phase of activation, and to transient activation of p38 mitogen-activated protein kinase (p38 MAPK) in Aplysia …

On The Origin Of Sensory Errors, Jonathan R. Flynn

Dissertations & Theses (Open Access)

Estimation of perceptual variables is imprecise and prone to errors. Although the properties of these perceptual errors are well characterized, the physiological basis for these errors is unknown. One previously proposed explanation for these errors is the trial-by-trial variability of the responses of sensory neurons that encode the percept. Initially, it would seem that a complicated electrophysiological experiment would need to be performed to test this hypothesis. However, using a strong theoretical framework, I demonstrate that it is possible to determine statistical characteristics of the physiological mechanism responsible for perceptual errors solely from a behavioral experiment. The basis for this …