Abstract

The theoretical mechanisms underlying the symptoms of Parkinson’s disease are based on dysfunctional output from the basal ganglia projected to the cortex via the thalamus. However, the subthalamic nucleus (STN) and substantia nigra pars reticularis (SNr) as part of the basal ganglia, also project to the brainstem, in particular to the pedunculopontine nucleus (PPN). Both the STN and SNr have altered neuronal activity in the 6-hydroxydopamine (6-OHDA) Parkinson’s model rat. Thus, it is hypothesized that the PPN is altered in this model of Parkinson’s disease.

This hypothesis was examined by comparing the rates of glucose metabolism and spontaneous neuronal activity of the NADPH diaphorase histologically identified PPN between unilateral 6-OHDA lesioned, sham lesioned, and normals rats. All 6-OHDA lesioned rats in these studies rotated to apomorphine and had more than 97.5% dopamine loss in biopsies of the striatum measured with high pressure liquid chromatography coupled to electrochemical detection. There was a significant 9% increase in glucose metabolism in the PPN on the lesioned side compared to the nonlesioned side of the 6-OHDA rat (P < 0.05). Under light Halothane anesthesia, there was a significant increase in the spontaneous neuronal activity of the PPN in a subpopulation of cells unresponsive to a noxious tail pinch compared to normals (P < 0.01). Systemic apomorphine administration altered the spontaneous firing rate in 23 of 41 cells in the PPN area, demonstrating a functional link between the basal ganglia and the PPN. These metabolic and neurophysiological changes in the PPN demonstrate that the PPN is altered in the unilateral 6-OHDA Parkinson’s model rat, confirming the anatomical connection between the basal ganglia and the brainstem. This raises the possibility of altered brainstem functions in Parkinson’s disease, producing the walking and sleep related symptoms of Parkinson’s disease.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

George Maeda

Second Advisor

John Buchholtz

Third Advisor

Robert P. Iacono

Fourth Advisor

Michael Kirby

Fifth Advisor

Robert Pearlstein

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1999

Date (Title Page)

9-1999

Language

English

Library of Congress/MESH Subject Headings

Parkinson Disease.

Type

Dissertation

Page Count

xi; 200

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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