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Improving Therapeutics for Parkinson's Disease

O'Malley, Jennifer A.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1259079683

Abstract Details

2009, PhD, University of Cincinnati, Medicine : Pathobiology and Molecular Medicine.
The following results are from studies designed with the overall goal of elucidating means for improving therapeutics for Parkinson’s disease. There is still much to be understood regarding the cellular and molecular mechanisms underlying the development of side effects to therapies for Parkinson’s disease such as levodopa-induced dyskinesias. Additionally, therapeutic intervention is further complicated when one considers the role of the functionally waning host environment, especially in the context of its responsivity to therapeutic agents. The work in this thesis was designed to focus on two aspects of Parkinson’s disease therapeutics, (1) improving graft efficacy by contributing additional information on how the host environment in regards to age impacts graft function in Parkinson’s disease, and (2) determining whether specific morphological changes of the nigral target neurons within the striatum impact development or severity of levodopa-induced dyskinesias. The first study demonstrates that while the aging striatum can, under specific conditions, support the survival of large numbers of grafted embryonic dopamine neurons, there is limited functional benefit even with robust cell survival. This realization is an important contribution to the field as it newly suggests the aged striatum is capable of supporting grafted dopamine neurons, but the limited efficacy of these grafts demonstrates the importance of the intricate balance between grafted cells and the aged host environment. The second study demonstrate that maintaining appropriate synaptic contacts that are presumably maintained when striatal medium spiny neuron cytoarchitecture is preserved, resulting in reduced drug-induced side-effects in parkinsonian rats. Future experiments are needed to explore the specific requirements of the aging striatum for functional recovery and how to implement synaptic stability of medium spiny neurons in clinical practice to potentially decrease side-effects of dopamine replacement pharmacotherapy.
Kathy Steece-Collier, PhD (Committee Chair)
David Richards, PhD (Committee Member)
Michael Behbehani, PhD (Committee Member)
John Bissler, MD (Committee Member)
Kim Seroogy, PhD (Committee Member)
Timothy Collier, PhD (Committee Member)
394 p.
Surgery
Parkinson; dopamine; dyskinesia; levodopa; dendritic spine; medium spiny neuron

Recommended Citations

Citations

  • O'Malley, J. A. (2009). Improving Therapeutics for Parkinson's Disease [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1259079683

    APA Style (7th edition)

  • O'Malley, Jennifer. Improving Therapeutics for Parkinson's Disease. 2009. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1259079683.

    MLA Style (8th edition)

  • O'Malley, Jennifer. "Improving Therapeutics for Parkinson's Disease." Doctoral dissertation, University of Cincinnati, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1259079683

    Chicago Manual of Style (17th edition)

ucin1259079683
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© 2009, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.