Department of Neurology.
Department of Pharmacology.
Toxicol Sci. 2017 Sep 1;159(1):170-178. doi: 10.1093/toxsci/kfx126.
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 [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.
农药暴露与帕金森病有关,帕金森病是一种神经退行性疾病,其特征是基底神经节(BG)中的黑质多巴胺细胞丧失,通常呈不对称性。我们之前报道过,暴露于农药的农业工人(AW)的黑质弥散张量成像(DTI)发生了变化。本研究旨在证实这一发现,并使用独立的样本人群探索其在 BG 结构中的半球和区域特异性。从 20 名有慢性农药暴露史的农业工人(AW)和 11 名对照中获得了农药暴露史、标准神经系统检查、高分辨率磁共振成像(T1/T2 加权和 DTI)和 [123I]碘氟烷 SPECT 图像(用于量化纹状体多巴胺转运体)。根据累积暴露农药的中位数天数,AW 被分为高(AWHi,n=10)和低(AWLo,n=10)暴露组。在每个半球中,量化了 BG(黑质、壳核、尾状核和苍白球[GP])各向异性分数(FA)、平均弥散度(MD)和纹状体 [123I]碘氟烷结合,并使用方差分析比较暴露组之间的差异。与对照组相比,AW 的左侧(但不是右侧)黑质和 GP 的 FA 明显降低(p 值<.029)。AW 和对照组之间的纹状体(壳核和尾状核)DTI 或 [123I]碘氟烷结合测量值无差异。亚组分析表明,仅在 AWHi 组(p≤.037)而不是 AWLo 组中存在明显的左侧黑质和 GP DTI 变化。AW,尤其是那些有更高农药暴露史的,表现出黑质和 GP 中的侧化微观结构变化,而纹状体区域似乎相对不受影响。未来的研究应该阐明环境毒物如何导致大脑易感性的差异和区域特异性的侧化。