Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

12-2008

Committee Chair or Co-Chairs

Antonio E. Rusinol, Barney E. Miller, Gregory A. Ordway, Merry Miller, Ronald H. Baisden

Abstract

The α7 subunit of the nicotinic receptor, a ligand gated ion channel with an affinity for nicotine, has long been implicated in the pathophysiology of schizophrenia due to the extremely high rate of smoking within the patient population. However, the exact role of the receptor has never fully been determined. In the following studies, various functions the receptor may assume in disease state are evaluated. There is a strong relationship between the immune system and schizophrenia, with the α7 subunit possibly serving as the link between the two. One of the following studies looks at the possibility of the receptor functioning as antigen in an autoimmune response. Blood sera of schizophrenic patients, as well as controls, were analyzed for the presence of antibodies to the α7 subunit of the nicotinic receptor. A sensitive ligand-based assay revealed schizophrenic patients could possess a pathogenic level of antibody that may exacerbate the degenerative nature of the disease, allowing for the possibility that receptor antibodies may serve as a contributing factor in the etiology of the disorder in at least a subset of patients. In other studies, the expression of the α7 receptor was investigated. Recombinant α7 receptor production has eluded researchers in non-mammalian species and this was the focus of our initial studies. In general, the lack of sufficient molecular recombinant techniques utilizing the receptor makes characterization of the α7 receptor and it's specific protein interactions difficult to evaluate. The regulatory mechanisms of the nicotinic receptor α7 subunit production and receptor formation have yet to be completely elucidated. Results in this investigation found a relationship between a functional CRE-element in the promoter region.

Document Type

Dissertation - Open Access

Copyright

Copyright by the authors.

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