Morris K. Udall Center of Excellence for Parkinson’s Disease Research at Michigan State University
Aging and Parkinson’s Disease: Models of Therapeutics and Neurologic Comorbidity.
Director: Timothy J. Collier, Ph.D.
Central Theme and Center Structure
The Udall Center at Michigan State University focuses on studies of two aspects of Parkinson’s disease (PD): neural mechanisms associated with development of adverse consequences of disease and treatment, and mechanisms associated with translational therapeutics. In addition, it long has been appreciated that advancing age is a primary risk factor for PD, yet aging rarely is incorporated into experimental studies. Thus, our Center groups these topics under the rubric of “adaptive and maladaptive plasticity” and examines their expression in the context of advancing chronological age. The proposed studies examine such themes as (1) the roles of altered dendritic morphology in projection neurons of the dopamine (DA) depleted striatum in the expression of therapy-induced dyskinesias; (2) exploration of mechanisms associated with electrical stimulation of the subthalamic nucleus (STN) that may promote neuroprotection of the nigrostriatal system; (3) examination of the hypothesis that grafted undifferentiated neural progenitor cells protect and repair the nigrostriatal system not by replacing lost DA neurons but by stimulating plasticity in the host brain; and (4) begin to study the known association of depression with PD to determine whether stress, chronic anxiety and depression exacerbate neurodegeneration and whether manipulation of these states influences the efficacy of therapeutic interventions. A critical aspect of all of the proposed projects will be to incorporate the recurring factor of advancing chronological age on the expression of mechanisms and outcomes derived from therapeutic interventions. Our goal is that through continued study of these issues our work can provide for development of optimal therapeutics for PD, inform their use in the clinical setting, and ultimately improve the quality of life for those living with PD.
The Udall Center assembles six principal investigators at two institutions to provide a team-based approach to our studies: Timothy Collier, Ph.D, (Director, Michigan State University), James Herman, Ph.D. (University of Cincinnati), Jack Lipton, Ph.D. (Michigan State University), Kim Seroogy, Ph.D. (University of Cincinnati), Caryl Sortwell, Ph.D. (Michigan State University), and Kathy Steece-Collier, Ph.D. (Michigan State University). The Center includes an Administrative Core to coordinate activities and communications associated with the projects, and an Analytical Chemistry, Gene Expression, and Surgical Core to provide the animal model and analytical endpoints common to all projects.
For more information on the Udall Centers program please visit: www.ninds.nih.gov/research/parkinsonsweb/udall_centers/index.htm
Udall Projects and Cores
Project 1: Profiles of maladaptive plasticity: Impact on graft and levodopa efficacy
Project Leader: Kathy Steece-Collier, Ph.D.
Project 2: STN Deep Brain Stimulation and Neuroprotection
Project Leader: Caryl E. Sortwell, Ph.D.
Project 3: Induction of Dopamine System Plasticity by Grafted Undifferentiated Progenitor Cells
Project Leader: Timothy J. Collier, Ph.D.
Project 4: Glucocorticoid mechanisms of stress-induced depression and parkinsonian symptomology
Project Leaders: Kim Seroogy, Ph.D. and James Herman, Ph.D.
Core A: Administrative
Project Leader: Timothy J. Collier, Ph.D.
Core B: Analytical, Surgical and Gene Expression
Project Leader: Jack W. Lipton, Ph.D.
Public Health Statement
Two aspects of Parkinson’s disease (PD) that have received relatively little study are the nervous system mechanisms associated with development of adverse consequences of disease and treatment (stress, depression and medication-induced side-effects) and mechanisms associated with experimental therapies (deep brain stimulation, cell transplantation). In addition, it long has been appreciated that advancing age is a primary risk factor for PD, yet aging rarely is incorporated into experimental studies. Our Center studies these adaptive and maladaptive changes associated with PD and its’ treatments in model systems that incorporate the factor of advancing chronological age. Our findings suggest that many negative side-effects of disease and treatment can be avoided or improved, and that experimental therapies currently in development may possess previously unrecognized additional benefits. Our goal is that through continued study of these issues our work can provide for development of optimal therapeutics for PD, inform their use in the clinical setting, and ultimately improve the quality of life for those living with PD.
