Publication Date
2014
Document Type
Thesis
Committee Members
Mark Rich, M.D., Ph.D. (Committee Chair); Sheila Fleming, Ph.D. (Committee Member); John Holden, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Abnormal accumulation of the presynaptic protein alpha-synuclein (aSyn) is associated with both familial and sporadic forms of Parkinson's disease. ATP13A2 is a lysosomal protein involved in protein degradation, including aSyn. Mice with a loss of ATP13A2 function develop age-related sensorimotor impairments and, in the brain, enhanced lipofuscin and insoluble aSyn accumulation. To further examine the potential interaction between aSyn and ATP13A2, aSyn overexpressing mice (aSyn) were crossbred with Atp13a2-defeicient (13a2) mice. Wildtype (WT), 13a2, aSyn, and double mutant aSyn/13a2 mice were generated and tested behaviorally at 3 ages. Sensorimotor function and cognition were examined using a battery of behavioral tests. Analysis of males and females revealed aSyn/13a2s make more errors on the beam, show increased hyperactivity and impulsivity, and build smaller nests compared to WTs. Female aSyn/13a2s display an earlier and progressive phenotype, suggesting increased aSyn burden combined with loss of ATP13A2 function alters sensorimotor function and cognition in mice.
Page Count
164
Department or Program
Department of Neuroscience, Cell Biology and Physiology
Year Degree Awarded
2014
Copyright
Copyright 2014, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
