Objective: To investigate the associations between manganese (Mn) exposure, D2 dopamine receptors (D2Rs), and parkinsonism using [C](N-methyl)benperidol (NMB) PET.
Methods: We used NMB PET to evaluate 50 workers with a range of Mn exposure: 22 Mn-exposed welders, 15 Mn-exposed workers, and 13 nonexposed workers. Cumulative Mn exposure was estimated from work histories, and movement disorder specialists examined all workers. We calculated NMB D2R nondisplaceable binding potential (BPND) for the striatum, globus pallidus, thalamus, and substantia nigra (SN). Multivariate analysis of covariance with post hoc descriptive discriminate analysis identified regional differences by exposure group. We used linear regression to examine the association among Mn exposure, Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) score, and regional D2R BPND.
Results: D2R BPND in the SN had the greatest discriminant power among exposure groups ( < 0.01). Age-adjusted SN D2R BPND was 0.073 (95% confidence interval [CI] 0.022-0.124) greater in Mn-exposed welders and 0.068 (95% CI 0.013-0.124) greater in Mn-exposed workers compared to nonexposed workers. After adjustment for age, SN D2R BPND was 0.0021 (95% CI 0.0005-0.0042) higher for each year of Mn exposure. Each 0.10 increase in SN D2R BPND was associated with a 2.65 (95% CI 0.56-4.75) increase in UPDRS3 score.
Conclusions And Relevance: Nigral D2R BPND increased with Mn exposure and clinical parkinsonism, indicating dose-dependent dopaminergic dysfunction of the SN in Mn neurotoxicity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140373 | PMC |
| http://dx.doi.org/10.1212/WNL.0000000000006163 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Reserpine-induced rat model for depression: Behavioral, physiological and PET-based dopamine receptor availability validation.
Prog Neuropsychopharmacol Biol Psychiatry
July 2024
Lab of Stereotaxy and Interventional Neurosciences (SIN), Dept. of Stereotactic and Functional Neurosurgery, Medical Center - University Freiburg, Germany; Department of Stereotactic and Functional Neurosurgery, Medical Center - University Freiburg, Germany; Faculty of Biology, University of Freiburg, Germany; Center for Basics in Neuromodulation, University of Freiburg, Freiburg, Germany. Electronic address:
Background: Reserpine (RES), a Vesicular Monoamine Transporter 2 (VMAT) inhibitor agent, has been used in preclinical research for many years to create animal models for depression and to test experimental antidepressant strategies. Nevertheless, evidence of the potential use and validity of RES as a chronic pharmacological model for depression is lacking, and there are no comprehensive studies of the behavioral effects in conjunction with molecular outcomes.
Methods: Experiment 1.
Association of protein distribution and gene expression revealed by positron emission tomography and postmortem gene expression in the dopaminergic system of the human brain.
Eur J Nucl Med Mol Imaging
November 2023
Department of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage, Chiba, 263-8555, Japan.
Purpose: The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new opportunities to understand the influence of regulation after transcription on protein distribution. Previous studies have reported that messenger (m)-RNA expression levels spatially correlate with the density maps of serotonin receptors but not with those of transporters.
View Article and Find Full Text PDFSex steroid hormone levels associated with dopamine D receptor availability in people who smoke cigarettes.
Front Behav Neurosci
June 2023
Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, United States.
Introduction: Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes.
View Article and Find Full Text PDFLower Dopamine D2/3 Receptor Availability is Associated With Worse Verbal Learning and Memory in People Who Smoke Cigarettes.
Nicotine Tob Res
April 2023
Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA.
Introduction: Tobacco smoking is a major public health burden. The mesocortical dopamine system-including the dorsolateral prefrontal cortex (dlPFC)-plays an important role in cognitive function. Dysregulated dopamine signaling in dlPFC is associated with cognitive deficits such as impairments in attention, learning, working memory, and inhibitory control.
View Article and Find Full Text PDFThalamic dopamine D2-receptor availability in schizophrenia: a study on antipsychotic-naive patients with first-episode psychosis and a meta-analysis.
Mol Psychiatry
February 2022
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Article Synopsis
- The study examines the role of dopamine D2-receptors (D2-R) in schizophrenia, specifically comparing these receptors in the thalamus between first-episode psychosis patients and healthy controls.
- Patients showed significantly lower D2-R binding in the whole thalamus and especially in areas connected to the frontal cortex, which could indicate a disruption in thalamocortical connectivity.
- Further analyses revealed lower diffusion tensor imaging (DTI) values in patients, suggesting impaired connectivity that could contribute to the symptoms of schizophrenia.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!