title: Microstructural changes in the substantia nigra of asymptomatic agricultural workers.
abstract: Parkinson's disease (PD) is marked by the loss of dopamine neurons in the substantia nigra (SN). Although the exact etiology is unknown, sporadic PD is hypothesized to be a result of genetic susceptibility interacting with environmental insult. Epidemiological studies suggest that pesticide exposure is linked to higher PD risk, but there are no studies demonstrating SN changes with chronic pesticide exposure in human subjects. Thus, high resolution T2-weighted magnetic resonance imaging (MRI) and diffusion tensor (DTI) images were obtained from 12 agricultural workers with chronic pesticide exposure, 12 controls, and 12 PD subjects. Neither controls nor pesticide-exposed subjects, had any parkinsonian symptoms. Exposure history to pesticides was assessed by a structured questionnaire. DTI measures in the SN, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were obtained for all subjects and compared among groups. Compared to controls, PD patients showed the expected significant changes in all DTI measurements in the SN. The pesticide-exposed subjects, compared to controls, had significantly lower FA values (p=0.022, after multiple comparisons correction), but no significant differences in RD, MD, or AD measures. The study is the first to demonstrate microstructural changes in the SN of human subjects with chronic pesticide exposure. The changes detected by MRI may mark "one of the hits" leading to PD, and underlie the increased risk of PD in pesticide users found in epidemiological studies. Further human studies assisted by these imaging markers may be useful in understanding the etiology of PD.
authors: Departments of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors: Guangwei
authors: G
authors: Du
authors: Departments of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Departments of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors: Mechelle M
authors: MM
authors: Lewis
authors: Departments of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors: Nicholas W
authors: NW
authors: Sterling
authors: Departments of Public Health Sciences, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors: Lan
authors: L
authors: Kong
authors: National Institute of Environmental Health Sciences, Research Triangle Park, NC 27705, USA.
authors: Honglei
authors: H
authors: Chen
authors: Departments of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Departments of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors: Richard B
authors: RB
authors: Mailman
authors: Departments of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Departments of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Departments of Radiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Departments of Neurosurgery, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Departments of Kinesiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Departments of Bioengineering, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA. Electronic address: xuemei@psu.edu.
authors: Xuemei
authors: X
authors: Huang
mesh_terms: D000328:Adult; D000383:Agriculture; D000704:Analysis of Variance; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010300:Parkinson Disease / Q000473:pathology*; D010575:Pesticides; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology*
chemical_list: D010575:Pesticides
keywords: Diffusion tensor imaging (DTI); Magnetic resonance imaging (MRI); Paraquat; Parkinson's disease (PD); Pesticides; Substantia nigra (SN)