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Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease

OBJECTIVE: People with Parkinson disease (PD) frequently develop dementia, which is associated with neocortical deposition of alpha-synuclein (α-syn) in Lewy bodies and Lewy neurites. In addition, neuronal loss and deposition of aggregated α-syn also occur in multiple subcortical nuclei that project...

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Autores principales: Buddhala, Chandana, Loftin, Susan K, Kuley, Brandon M, Cairns, Nigel J, Campbell, Meghan C, Perlmutter, Joel S, Kotzbauer, Paul T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603378/
https://www.ncbi.nlm.nih.gov/pubmed/26478895
http://dx.doi.org/10.1002/acn3.246
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author Buddhala, Chandana
Loftin, Susan K
Kuley, Brandon M
Cairns, Nigel J
Campbell, Meghan C
Perlmutter, Joel S
Kotzbauer, Paul T
author_facet Buddhala, Chandana
Loftin, Susan K
Kuley, Brandon M
Cairns, Nigel J
Campbell, Meghan C
Perlmutter, Joel S
Kotzbauer, Paul T
author_sort Buddhala, Chandana
collection PubMed
description OBJECTIVE: People with Parkinson disease (PD) frequently develop dementia, which is associated with neocortical deposition of alpha-synuclein (α-syn) in Lewy bodies and Lewy neurites. In addition, neuronal loss and deposition of aggregated α-syn also occur in multiple subcortical nuclei that project to neocortical, limbic, and basal ganglia regions. Therefore, we quantified regional deficits in innervation from these PD-affected subcortical nuclei, by measuring the neurotransmitters and neurotransmitter transporter proteins originating from projections of dopaminergic neurons in substantia nigra pars compacta, serotonergic neurons in dorsal raphé nuclei, noradrenergic neurons in locus coeruleus, and cholinergic neurons in nucleus basalis of Meynert. METHODS: High-performance liquid chromatography and novel enzyme-linked immunosorbent assays were performed to quantify dopaminergic, serotonergic, noradrenergic, and cholinergic innervation in postmortem brain tissue. Eight brain regions from 15 PD participants (with dementia and Braak stage 6 α-syn deposition) and six age-matched controls were tested. RESULTS: PD participants compared to controls had widespread reductions of dopamine transporter in caudate, amygdala, hippocampus, inferior parietal lobule (IPL), precuneus, and visual association cortex (VAC) that exceeded loss of dopamine, which was only significantly reduced in caudate and amygdala. In contrast, PD participants had comparable deficits of both serotonin and serotonin transporter in caudate, middle frontal gyrus, IPL, and VAC. PD participants also had significantly reduced norepinephrine levels for all eight brain regions tested. Vesicular acetylcholine transporter levels were only quantifiable in caudate and hippocampus and did not differ between PD and control groups. INTERPRETATION: These results demonstrate widespread deficits in dopaminergic, serotonergic, and noradrenergic innervation of neocortical, limbic, and basal ganglia regions in advanced PD with dementia.
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spelling pubmed-46033782015-10-16 Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease Buddhala, Chandana Loftin, Susan K Kuley, Brandon M Cairns, Nigel J Campbell, Meghan C Perlmutter, Joel S Kotzbauer, Paul T Ann Clin Transl Neurol Research Articles OBJECTIVE: People with Parkinson disease (PD) frequently develop dementia, which is associated with neocortical deposition of alpha-synuclein (α-syn) in Lewy bodies and Lewy neurites. In addition, neuronal loss and deposition of aggregated α-syn also occur in multiple subcortical nuclei that project to neocortical, limbic, and basal ganglia regions. Therefore, we quantified regional deficits in innervation from these PD-affected subcortical nuclei, by measuring the neurotransmitters and neurotransmitter transporter proteins originating from projections of dopaminergic neurons in substantia nigra pars compacta, serotonergic neurons in dorsal raphé nuclei, noradrenergic neurons in locus coeruleus, and cholinergic neurons in nucleus basalis of Meynert. METHODS: High-performance liquid chromatography and novel enzyme-linked immunosorbent assays were performed to quantify dopaminergic, serotonergic, noradrenergic, and cholinergic innervation in postmortem brain tissue. Eight brain regions from 15 PD participants (with dementia and Braak stage 6 α-syn deposition) and six age-matched controls were tested. RESULTS: PD participants compared to controls had widespread reductions of dopamine transporter in caudate, amygdala, hippocampus, inferior parietal lobule (IPL), precuneus, and visual association cortex (VAC) that exceeded loss of dopamine, which was only significantly reduced in caudate and amygdala. In contrast, PD participants had comparable deficits of both serotonin and serotonin transporter in caudate, middle frontal gyrus, IPL, and VAC. PD participants also had significantly reduced norepinephrine levels for all eight brain regions tested. Vesicular acetylcholine transporter levels were only quantifiable in caudate and hippocampus and did not differ between PD and control groups. INTERPRETATION: These results demonstrate widespread deficits in dopaminergic, serotonergic, and noradrenergic innervation of neocortical, limbic, and basal ganglia regions in advanced PD with dementia. John Wiley & Sons, Ltd 2015-10 2015-09-12 /pmc/articles/PMC4603378/ /pubmed/26478895 http://dx.doi.org/10.1002/acn3.246 Text en © 2015 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Buddhala, Chandana
Loftin, Susan K
Kuley, Brandon M
Cairns, Nigel J
Campbell, Meghan C
Perlmutter, Joel S
Kotzbauer, Paul T
Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
title Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
title_full Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
title_fullStr Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
title_full_unstemmed Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
title_short Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
title_sort dopaminergic, serotonergic, and noradrenergic deficits in parkinson disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603378/
https://www.ncbi.nlm.nih.gov/pubmed/26478895
http://dx.doi.org/10.1002/acn3.246
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