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Cholinergic dysfunction in occupational manganese exposure.

T Noah Hutson1, Susan Searles Nielsen2, Natalie Senini1

  • 1Department of Neurology, Barrow Neurological Institute, 240 W Thomas Rd, Phoenix, AZ 85013, USA.

Neurotoxicology
|September 5, 2025
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Summary
This summary is machine-generated.

Manganese (Mn) exposure lowers brain cholinergic activity, impacting cognitive control and verbal fluency. This cholinergic dysfunction may serve as an early biomarker for Mn neurotoxicity and parkinsonian syndromes.

Keywords:
BiomarkersCholinergicManganeseNeurotoxicologyPET

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Area of Science:

  • Neuroscience
  • Toxicology
  • Radiochemistry

Background:

  • Manganese (Mn) overexposure causes parkinsonism and cognitive deficits.
  • Mechanisms of Mn neurotoxicity are not fully understood.
  • Cholinergic system's role in Mn-induced cognitive impairment requires further investigation.

Purpose of the Study:

  • To investigate the relationship between Mn exposure and brain cholinergic function.
  • To assess how cholinergic function mediates cognitive impairment in Mn-exposed workers.
  • To identify potential biomarkers of early Mn neurotoxicity.

Main Methods:

  • Positron emission tomography (PET) with a vesicular acetylcholine transporter (VAChT) radiotracer (VAT) to assess brain cholinergic function.
  • Occupational Mn exposure estimation via work histories and MRI pallidal index.
  • Cognitive control assessment using a battery of tests including Verbal Fluency (VF).

Main Results:

  • Mn exposure correlated with reduced cholinergic VAT binding in the caudate and cortical regions.
  • Cholinergic function significantly mediated the association between Mn exposure and cognitive control performance.
  • Cholinergic deficits were linked to impaired Verbal Fluency (VF).

Conclusions:

  • Elevated Mn exposure is associated with decreased cholinergic activity in key brain areas.
  • Cholinergic dysfunction is a key mechanism linking Mn exposure to cognitive deficits.
  • Caudate and cortical cholinergic activity may indicate early Mn neurotoxicity and parkinsonian syndromes.