Loss of the Cortical Monoamine Projection Systems in the MPTP-treated Nonhuman Primate Model of Parkinson's Disease Open Access

Abstract

The condition produced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the nonhuman primate clearly models the striatal and nigral dopamine deficiency found in Parkinson's disease (PD). However, evidence supporting its ability to mimic changes outside the nigrostriatal dopaminergic system known to occur in the idiopathic disease is controversial. In order to further assess the validity of the MPTP-treated monkey model of PD, this study investigated the changes in the serotonin and catecholamine cortical projections in nonhuman primates rendered parkinsonian following chronic exposure to MPTP. Quantitative analysis of immunohistochemical staining with antibodies raised against tyrosine hydroxylase (TH) and serotonin (5HT) in various cortical areas involved in cognitive, limbic and motor functions was compared between normal and parkinsonian animals. In normal monkeys, TH and serotonin-positive axons and terminals densely innervated all cortical areas. However, in the MPTP-treated monkeys a reduction of innervation for both transmitter systems that ranged from 17.77 to 76.08 % of control values was found in all cortical regions, but the most striking denervation was found in limbic and motor areas for TH and in the motor areas for serotonin. These findings demonstrate that the pathology of monoamine networks in the MPTP-treated nonhuman primate as a model for PD extends beyond the nigrostriatal dopaminergic system.

Table of Contents

Table of Contents
Introduction...1
Materials and Method...8
Results...12
Discussion...13
References...20
Table 1...29
Table 2...30
Table 3...31
Figure 1...32
Figure 2...33
Figure 3...34
Figure 4...35
Figure 5...36
Figure 6...37
Figure 7...38
Figure 8...39
Figure 9...40
Figure 10...41
Figure 11...42

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Keyword	nonhuman primate monoamine MPTP cortex Parkinson's disease
Committee Chair / Thesis Advisor	Smith, Yoland, Emory University
Committee Members	Crutcher, Michael D, Emory University Jaeger, Dieter, Emory University

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