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Title page for ETD etd-07252007-155530


Type of Document Dissertation
Author Brown, Abigail Maureen
URN etd-07252007-155530
Title Dopamine depletion alters the balance between CA2+/calmodulin-dependent protein kinase II and protein phosphatase I
Degree PhD
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
Danny Winder Committee Chair
Anne Kenworthy Committee Member
Ariel Deutch Committee Member
Jackie Corbin Committee Member
Pat Levitt Committee Member
Keywords
  • Parkinson's Disease -- Pathophysiology
  • Dopamine
  • CaMKII
  • phosphatase
  • Dopaminergic neurons
Date of Defense 2006-08-11
Availability unrestricted
Abstract
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

Parkinson’s 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 Parkinson’s 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 Parkinson’s 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 Parkinson’s disease.

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