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Published on: July 12, 2012
Thalamic GABA levels and occupational manganese neurotoxicity: Association with exposure levels and brain MRI
Ruoyun E Ma1, Eric J Ward2, Chien-Lin Yeh1
1School of Health Sciences, Purdue University, West Lafayette, IN, USA; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract:
Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13±0.1mg/m3; High: N=13; mean air Mn=0.23±0.18mg/m3), as well as unexposed control workers (N=22, mean air Mn=0.002±0.001mg/m3) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect.
Insights
Occupational manganese (Mn) exposure increases brain GABA levels and impairs motor function in welders, particularly at higher exposure levels. These effects suggest a potential threshold for manganese toxicity, impacting the GABAergic system before symptoms appear.
Area of Science:
- Neuroscience
- Occupational Health
- Toxicology
Background:
- Occupational manganese (Mn) exposure is linked to Parkinsonism-like symptoms, affecting cognitive and motor functions.
- The brain's neurotransmitter system may be disrupted by Mn intoxication before clinical symptoms manifest.
- Edited Magnetic Resonance Spectroscopy (MRS) allows non-invasive in vivo measurement of neurometabolites like GABA in Mn-exposed workers.
Purpose of the Study:
- To investigate the effects of chronic Mn exposure on the thalamic GABAergic system in welders.
- To correlate Mn exposure levels with neurological and neurochemical changes.
- To explore the relationship between Mn deposition in the brain and alterations in GABAergic function.
Main Methods:
- Utilized Magnetic Resonance Imaging (MRI), MRS, personal air sampling, work history questionnaires, and UPDRS-III neurological assessment.
- Recruited 39 welders with varying Mn exposure levels (Low and High) and 22 unexposed controls.
- Analyzed thalamic GABA levels, motor function, and Mn deposition in brain regions like the substantia nigra and globus pallidus.
Main Results:
- Higher Mn exposure in welders significantly increased thalamic GABA levels by 45% and worsened general motor function.
- Lower Mn exposure groups did not show significant differences in GABA levels or motor performance compared to controls.
- Thalamic GABA levels were best predicted by recent Mn exposure and influenced by Mn deposition in specific brain areas, indicating a threshold effect.
Conclusions:
- Chronic, high-level occupational manganese exposure alters the thalamic GABAergic system and impairs motor function in welders.
- A non-linear dose-response relationship, suggesting a threshold effect, was observed for both thalamic GABA levels and motor function.
- These findings highlight the potential for early neurochemical changes in response to manganese exposure, preceding overt neurological symptoms.
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