MOLECULAR PHYSIOLOGY AND BIOPHYSICS
DOPAMINE DEPLETION ALTERS THE BALANCE BETWEEN CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE II AND PROTEIN PHOSPHATASE I
ABIGAIL M. BROWN
Dissertation under the direction of Professor Roger J. Colbran
Parkinsons disease is characterized by the preferential loss of the nigrostriatal dopaminergic neurons, whose axons terminate within the striatum and release dopamine onto medium spiny neurons. Striatal dopamine loss results in several changes in striatal medium spiny neuron morphology and disrupts corticostriatal synaptic plasticity. However, the molecular and biochemical mechanisms underlying the consequences of dopamine loss in Parkinsons disease are not well understood. This dissertation presents evidence linking both short-term and chronic dopamine loss to the misregulation of two key synaptic signaling enzymes in the striatum, CaMKII and PP1. Although it is unclear what causes Parkinsons disease in most human patients, the possibility that such striatal calcium-sensitive signaling pathways are misregulated suggests that targeting these pathways may be a useful strategy in developing future treatments for Parkinsons disease.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07252007-155530 |
| Date | 31 July 2007 |
| Creators | Brown, Abigail Maureen |
| Contributors | Pat Levitt, Danny Winder, Anne Kenworthy, Jackie Corbin, Ariel Deutch |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07252007-155530/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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