TY - JOUR
T1 - Lateralized basal ganglia vulnerability to pesticide exposure in asymptomatic agricultural workers
AU - Lewis, Mechelle
AU - Sterling, Nicholas W.
AU - Du, Guangwei
AU - Lee, Eun Young
AU - Shyu, Grace
AU - Goldenberg, Michael
AU - Allen, Thomas
AU - Stetter, Christy
AU - Kong, Lan
AU - Snipes, Shedra Amy
AU - Jones, Byron C.
AU - Chen, Honglei
AU - Mailman, Richard
AU - Huang, Xuemei
N1 - Funding Information:
This work was supported in part by the National Institute of Neurological Disease and Stroke (NS060722 and NS082151 to X.H.), the National Institute of Environmental Health Sciences (ES022614 to B.C.J.), the Hershey Medical Center General Clinical Research Center (National Center for Research Resources, Grant UL1 RR033184 that is now at the National Center for Advancing Translational Sciences, Grant UL1 TR000127), and a GE HealthCare grant. All analyses, interpretations, and conclusions are those of the authors and not the research sponsors.
Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
PY - 2017
Y1 - 2017
N2 - Pesticide exposure is linked to Parkinson's disease, a neurodegenerative disorder marked by dopamine cell loss in the substantia nigra of the basal ganglia (BG) that often presents asymmetrically. We previously reported that pesticideexposed agricultural workers (AW) have nigral diffusion tensor imaging (DTI) changes. The current study sought to confirm this finding, and explore its hemisphere and regional specificity within BG structures using an independent sample population. Pesticide exposure history, standard neurological exam, high-resolution magnetic resonance imaging (T1/T2-weighted and DTI), and [123I]ioflupane SPECT images (to quantify striatal dopamine transporters) were obtained from 20 AW with chronic pesticide exposure and 11 controls. Based on median cumulative days of pesticide exposure, AW were subdivided into high (AWHi, n=10) and low (AWLo, n=10) exposure groups. BG (nigra, putamen, caudate, and globus pallidus [GP]) fractional anisotropy (FA), mean diffusivity (MD), and striatal [123I]ioflupane binding in each hemisphere were quantified, and compared across exposure groups using analysis of variance. Left, but not right, nigral and GP FA were significantly lower in AW compared with controls (p's <.029). None of the striatal (putamen and caudate) DTI or [123I]ioflupane binding measurements differed between AW and controls. Subgroup analyses indicated that significant left nigral and GP DTI changes were present only in the AWHi (p ≤.037) but not the AWLo subgroup. AW, especially those with higher pesticide exposure history, demonstrate lateralized microstructural changes in the nigra and GP, whereas striatal areas appear relatively unaffected. Future studies should elucidate how environmental toxicants cause differential lateralized- and regionally specific brain vulnerability.
AB - Pesticide exposure is linked to Parkinson's disease, a neurodegenerative disorder marked by dopamine cell loss in the substantia nigra of the basal ganglia (BG) that often presents asymmetrically. We previously reported that pesticideexposed agricultural workers (AW) have nigral diffusion tensor imaging (DTI) changes. The current study sought to confirm this finding, and explore its hemisphere and regional specificity within BG structures using an independent sample population. Pesticide exposure history, standard neurological exam, high-resolution magnetic resonance imaging (T1/T2-weighted and DTI), and [123I]ioflupane SPECT images (to quantify striatal dopamine transporters) were obtained from 20 AW with chronic pesticide exposure and 11 controls. Based on median cumulative days of pesticide exposure, AW were subdivided into high (AWHi, n=10) and low (AWLo, n=10) exposure groups. BG (nigra, putamen, caudate, and globus pallidus [GP]) fractional anisotropy (FA), mean diffusivity (MD), and striatal [123I]ioflupane binding in each hemisphere were quantified, and compared across exposure groups using analysis of variance. Left, but not right, nigral and GP FA were significantly lower in AW compared with controls (p's <.029). None of the striatal (putamen and caudate) DTI or [123I]ioflupane binding measurements differed between AW and controls. Subgroup analyses indicated that significant left nigral and GP DTI changes were present only in the AWHi (p ≤.037) but not the AWLo subgroup. AW, especially those with higher pesticide exposure history, demonstrate lateralized microstructural changes in the nigra and GP, whereas striatal areas appear relatively unaffected. Future studies should elucidate how environmental toxicants cause differential lateralized- and regionally specific brain vulnerability.
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U2 - 10.1093/TOXSCI/KFX126
DO - 10.1093/TOXSCI/KFX126
M3 - Article
C2 - 28633499
AN - SCOPUS:85048013892
VL - 159
SP - 170
EP - 178
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -