Thesis (M.S.)--University of Wisconsin--Madison, 1943. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

No description available.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. Although the etiology of the disease is yet to be fully elucidated, pathological hallmarks have been consistently described, including the accumulation of amyloid plaques, dysfunctional ionic homeostasis, synaptic disruption and neurodegeneration. The amyloid hypothesis postulates that aberrant production of amyloid-β (Aβ) proteins, which have a high propensity to aggregate, lies at the center of the pathological mechanism of AD. In particular, soluble oligomeric Aβ structures have been identified as primary toxic species. The interaction of these structures with several cellular targets, including ion channels such as nicotinic acetylcholine receptors (nAChR) and voltage operated Ca²⁺ channels (VOCC), has also been implicated in Aβ toxicity and AD. The aim of this thesis is to investigate how the acute and chronic actions of Aβ in vitro are affected by nicotinic ligands. Acute application of Aβ₁₋₄₂ to fluo-3-loaded PC12 cells potentiated Ca²₊ increases evoked by stimulation of nAChR and VOCC, while chronic application reduced redox potential, disrupted membrane integrity and initiated apoptosis in PC12 cells. In addition to mimicking the toxic responses of PC12 cells, Aβ₁₋₄₂ also reduced neurite outgrowth and synaptogenesis in rat primary cortical neurons. All actions of Aβ were prevented by inhibitors of Aβ₁₋₄₂ oligomerisation, including the hexapeptide KLVFFA. Neuroprotection afforded by (+)-nicotine also occurred via inhibition of Aβ₁₋₄₂ oligomerisation, rather than by a receptor-mediated mechanism. No other pharmacological approaches, including application of two novel ligands selective for α7 nAChR: the partial agonist SSR180711 and antagonist α-conotoxinArIB[V11L,V16D], characterized herein, protected against Aβ₁₋₄₂ toxicity. While inhibiting oligomerisation prevented the actions of Aβ₁₋₄₂, enhanced oligomerisation evoked amplified toxic responses. However, the potentiation of Ca²⁺ signalling diminished following enhanced oligomerisation. This, coupled with a lack of VOCC-involvement in Aβ toxicity and the differential actions of truncated Aβ peptides on toxicity and Ca²⁺ signaling, indicates that the acute disruption of Ca²⁺ signaling by Aβ does not underpin the chronic toxic effects of Aβ.

Thesis (Ph. D.)--University of Chicago, Committee on Neurobiology, 2002. / Includes bibliographical references. Also available on the Internet.

No description available.

Thesis (M.S.)--Ohio State University, 2008. / Title from first page of PDF file. Non-Latin script record Includes bibliographical references (p. 27-32).

Thesis (M.A.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on April 10, 2009) Includes bibliographical references.

Thesis (Ph. D.)--University of Chicago, Pritzker School of Medicine, Committee on Neurobiology, June 2002. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Chicago, Pritzker School of Medicine, Department of Neurobiology, Pharmacology, and Physiology, June 2002. / Includes bibliographical references. Also available on the Internet.