Eun-Young Lee1, Michael R Flynn2, Guangwei Du3, Mechelle M Lewis4, Michael Goldenberg5, Lan Kong6, Richard B Mailman7, Young-Seoub Hong8, Xuemei Huang9. 1. Department of Health Care and Science, Dong-A University, Busan, South Korea. Electronic address: enyoungee@dau.ac.kr. 2. Department of Kinesiology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Environmental Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA. Electronic address: mflynn@email.unc.edu. 3. Department of Neurology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA. Electronic address: guangweidu@pennstatehealth.psu.edu. 4. Department of Neurology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Pharmacology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA. Electronic address: mlewis5@pennstatehealth.psu.edu. 5. Department of Neurology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA. Electronic address: mgoldenberg@pennstatehealth.psu.edu. 6. Department of Public Health Sciences, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA. Electronic address: lkong@phs.psu.edu. 7. Department of Neurology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Pharmacology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA. Electronic address: rmailman@psu.edu. 8. Department of Preventive Medicine, Dong-A University College of Medicine, Busan, South Korea. Electronic address: yshong@dau.ac.kr. 9. Department of Neurology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Pharmacology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Radiology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Neurosurgery, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Kinesiology, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, 17033, USA; Department of Environmental Sciences, University of North Carolina, Chapel Hill, NC, 27599, USA. Electronic address: xuemei@psu.edu.
Abstract
INTRODUCTION: Manganese (Mn)-induced parkinsonism involves motor symptoms similar to those observed in Parkinson's disease (PD). Previous literature suggests that chronic Mn- exposure may increase PD risk, although Mn-induced clinical syndromes are considered atypical for PD. This study investigated whether asymptomatic welders display differences in the substantia nigra (SN), the key pathological locus of PD. METHOD: Brain MRI data and occupational exposure history were obtained in welders (N = 43) and matched controls (N = 31). Diffusion tensor imaging fractional anisotropy (FA; estimate of microstructural integrity) and R2* (estimate of iron and other PD-related brain differences) values in the SN pars compacta (SNc), SN reticulata (SNr), and globus pallidus (GP) were compared between the two groups. The MRI markers of the SN and GP within welders were related to exposure estimates. RESULTS: Compared to controls, welders who had chronic, but low-level, Mn-exposure had similar FA and R2* values in both SN regions (p's > 0.082), but significantly lower FA (p = 0.0013), although not R2* (p = 0.553), in the GP. In welders, FA values in the SN and GP showed a second-order polynomial relationship with cumulative lifetime welding exposure (p's < 0.03). CONCLUSION: Neurotoxic processes associated with Mn-exposure may be different from those in PD when the exposure-level is relatively low. Greater welding duration and level, however, were associated with FA differences in the GP and SN, indicating that welding exposures above a certain level may induce neurotoxicity in the SN, a finding that should be explored further in future studies.
INTRODUCTION: Manganese (Mn)-induced parkinsonism involves motor symptoms similar to those observed in Parkinson's disease (PD). Previous literature suggests that chronic Mn- exposure may increase PD risk, although Mn-induced clinical syndromes are considered atypical for PD. This study investigated whether asymptomatic welders display differences in the substantia nigra (SN), the key pathological locus of PD. METHOD: Brain MRI data and occupational exposure history were obtained in welders (N = 43) and matched controls (N = 31). Diffusion tensor imaging fractional anisotropy (FA; estimate of microstructural integrity) and R2* (estimate of iron and other PD-related brain differences) values in the SN pars compacta (SNc), SN reticulata (SNr), and globus pallidus (GP) were compared between the two groups. The MRI markers of the SN and GP within welders were related to exposure estimates. RESULTS: Compared to controls, welders who had chronic, but low-level, Mn-exposure had similar FA and R2* values in both SN regions (p's > 0.082), but significantly lower FA (p = 0.0013), although not R2* (p = 0.553), in the GP. In welders, FA values in the SN and GP showed a second-order polynomial relationship with cumulative lifetime welding exposure (p's < 0.03). CONCLUSION: Neurotoxic processes associated with Mn-exposure may be different from those in PD when the exposure-level is relatively low. Greater welding duration and level, however, were associated with FA differences in the GP and SN, indicating that welding exposures above a certain level may induce neurotoxicity in the SN, a finding that should be explored further in future studies.
Authors: Eun-Young Lee; Michael R Flynn; Guangwei Du; Mechelle M Lewis; Rebecca Fry; Amy H Herring; Eric Van Buren; Scott Van Buren; Lisa Smeester; Lan Kong; Qing Yang; Richard B Mailman; Xuemei Huang Journal: Toxicol Sci Date: 2015-05-07 Impact factor: 4.849
Authors: Guangwei Du; Mechelle M Lewis; Christopher Sica; Lu He; James R Connor; Lan Kong; Richard B Mailman; Xuemei Huang Journal: Mov Disord Date: 2018-05-14 Impact factor: 10.338
Authors: Eun-Young Lee; Michael R Flynn; Guangwei Du; Mechelle M Lewis; Amy H Herring; Eric Van Buren; Scott Van Buren; Lan Kong; Richard B Mailman; Xuemei Huang Journal: Toxicol Sci Date: 2016-07-27 Impact factor: 4.849