Tetrahydroisoquinoline Neurotoxins in Parkinson Disease
type: CreativeWork
description: The goal of this dissertation work was to (1) determine the distribution of several tetrahydroisoquinoline (TIQ) derivatives in rodent, normal human and Parkinson disease (PD) brain, (2) quantify the levels of these TIQ derivatives in common food sources in an effort to link specific food intake patterns with the development of PD and (3) examine the neurotoxicity of select TIQ derivatives in human dopaminergic cell culture. The TIQs are a family of monoamine alkaloids that share structural homology with 1-methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine (MPTP), can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death. In our studies, we utilize enantiomeric-selective high-performance liquid chromatography with electrochemical detection (HPLC-EC) and liquid chromatography with tandem mass spectroscopy (LC-MS/MS) to determine the concentrations of TIQ derivatives in brain, as well as in common dietary plants in the United States. The dopaminergic SH-SY5Y human neuroblastoma cell line was utilized to document the neurotoxicity of N-methylated salsolinol derivatives. Several TIQ derivatives were detected in all regions subjected to analysis. In general, salsolinols were present at higher concentrations than TIQ and its benzyl and methyl derivatives, especially in human brain. Moreover, salsolinols were concentrated in areas with increased dopamine synthesis and turnover such as the ventral midbrain and striatum, respectively. Significantly lower levels of (R)salsolinol, (S)salsolinol, N-methyl-(R)salsolinol andN-methyl-(S)salsolinol were found in the caudate nuclei of PD in comparison with normal human brain. N-methyl-norsalsolinol was detected in all regions of rodent and human brain subjected to analysis. In comparison to normal human controls, N-methyl-norsalsolinol levels were significantly lower in the substantia nigra and caudate nuclei from PD patients. N-methyl-norsalsolinol-immunoreactivity co-local…
abstract: The goal of this dissertation work was to (1) determine the distribution of several tetrahydroisoquinoline (TIQ) derivatives in rodent, normal human and Parkinson disease (PD) brain, (2) quantify the levels of these TIQ derivatives in common food sources in an effort to link specific food intake patterns with the development of PD and (3) examine the neurotoxicity of select TIQ derivatives in human dopaminergic cell culture. The TIQs are a family of monoamine alkaloids that share structural homology with 1-methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine (MPTP), can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death. In our studies, we utilize enantiomeric-selective high-performance liquid chromatography with electrochemical detection (HPLC-EC) and liquid chromatography with tandem mass spectroscopy (LC-MS/MS) to determine the concentrations of TIQ derivatives in brain, as well as in common dietary plants in the United States. The dopaminergic SH-SY5Y human neuroblastoma cell line was utilized to document the neurotoxicity of N-methylated salsolinol derivatives. Several TIQ derivatives were detected in all regions subjected to analysis. In general, salsolinols were present at higher concentrations than TIQ and its benzyl and methyl derivatives, especially in human brain. Moreover, salsolinols were concentrated in areas with increased dopamine synthesis and turnover such as the ventral midbrain and striatum, respectively. Significantly lower levels of (R)salsolinol, (S)salsolinol, N-methyl-(R)salsolinol andN-methyl-(S)salsolinol were found in the caudate nuclei of PD in comparison with normal human brain. N-methyl-norsalsolinol was detected in all regions of rodent and human brain subjected to analysis. In comparison to normal human controls, N-methyl-norsalsolinol levels were significantly lower in the substantia nigra and caudate nuclei from PD patients. N-methyl-norsalsolinol-immunoreactivity co-local…
author: DeCuypere, Michael G.
keywords: HPLC-EC, LC-MS/MS, Neurodegeneration, Neurotoxins, Parkinson Disease, Tetrahydroisoquinolines, Diseases, Medicine and Health Sciences, Nervous System Diseases, Neurosciences
date published: 2010-05-01T07:00:00Z
date modified: 2026-07-24T05:00:02Z
provider: University of Tennessee Health Science Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Tennessee Health Science Center