4.5 Article

Lateralized Basal Ganglia Vulnerability to Pesticide Exposure in Asymptomatic Agricultural Workers

Journal

TOXICOLOGICAL SCIENCES
Volume 159, Issue 1, Pages 170-178

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfx126

Keywords

substantia nigra; striatum; globus pallidus; MRI; DAT scan; pesticide exposure

Categories

Funding

  1. National Institute of Neurological Disease and Stroke [NS060722, NS082151]
  2. National Institute of Environmental Health Sciences [ES022614]
  3. National Center for Advancing Translational Sciences [UL1 TR000127]
  4. GE HealthCare grant

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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 pesticide-exposed 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 [I-123] 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 (AW(Hi), n = 10) and low (AW(Lo), n = 10) exposure groups. BG (nigra, putamen, caudate, and globus pallidus [GP]) fractional anisotropy (FA), mean diffusivity (MD), and striatal [I-123] 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 [I-123] ioflupane binding measurements differed between AW and controls. Subgroup analyses indicated that significant left nigral and GP DTI changes were present only in the AW(Hi) (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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