Selective D2 receptor PET in manganese-exposed workers.

Area of Science:

• Neuroscience
• Toxicology
• Radiology

Background:

• Manganese (Mn) is an essential element, but excessive exposure can lead to neurotoxicity.
• Parkinsonism is a neurological disorder characterized by motor symptoms, often associated with dopaminergic pathway dysfunction.

Purpose of the Study:

• To investigate the association between manganese exposure, D2 dopamine receptors (D2Rs), and parkinsonism.
• To utilize [11C](N-methyl)benperidol (NMB) Positron Emission Tomography (PET) for quantifying D2R availability in the brain.

Main Methods:

• NMB PET scans were performed on 50 workers with varying Mn exposure levels (welders, Mn-exposed workers, nonexposed controls).
• Cumulative Mn exposure was estimated, and clinical parkinsonism was assessed by movement disorder specialists.
• Nondisplaceable binding potential (BPND) of D2Rs was calculated for key brain regions, including the substantia nigra (SN).

Main Results:

• Substantia nigra (SN) D2R BPND showed the highest discriminant power between exposure groups.
• Mn-exposed workers exhibited significantly higher age-adjusted SN D2R BPND compared to nonexposed workers.
• Increased SN D2R BPND was dose-dependently associated with cumulative Mn exposure and higher Unified Parkinson's Disease Rating Scale motor scores (UPDRS3).

Conclusions:

• Nigral D2R BPND increases with Mn exposure and clinical parkinsonism.
• Findings indicate a dose-dependent dopaminergic dysfunction in the SN due to Mn neurotoxicity.
• NMB PET is a valuable tool for assessing Mn-induced neurotoxicity and its impact on the dopaminergic system.