Nicholas School of the Environment, Duke University, Durham, NC, USA.
Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA.
Neurotoxicol Teratol. 2021 Sep-Oct;87:107011. doi: 10.1016/j.ntt.2021.107011. Epub 2021 Jul 2.
Organophosphate (OP) compounds comprise one of the most widely used classes of insecticides worldwide. OPs have been shown to have negative human health impacts, particularly developmental neurotoxicity. However, neurotoxic impacts in later adulthood and during the aging process are relatively uncharacterized. The present study examined diazinon (DZN), an OP, to determine the neurobehavioral consequences, in addition to mitochondrial dysfunction on a macroscale (whole organism basal respiration) and on a microscale (whole organ mitochondrial respiration), using zebrafish (ZF) as a model. One group of 14-month-old adult ZF were exposed acutely as adults (0.4, 1.25, and 4.0 μM) for five days and tested as adults, and another group was exposed developmentally 5-120 h post-fertilization (70, 210, and 700 nM) and tested at larval, adolescent, adult, and aging life stages. ZF exposed acutely as adults did not display many significant neurobehavioral impacts or mitochondrial dysfunction. Conversely, the embryonically exposed ZF showed altered behavioral functions at each stage of life which emerged and attenuated as fish transitioned from each developmental stage to the next. Mitochondrial oxygen consumptions measurement results for developmentally DZN exposed ZF showed significant increases in the low and middle dose groups in organs such as the brain and testes. Overall, there is an indication that early developmental exposure to DZN had continuing adverse neurobehavioral and cellular consequences throughout their lives well into adulthood and aging periods.
有机磷（OP）化合物是世界上使用最广泛的杀虫剂之一。已证明 OPs 对人类健康有负面影响，特别是发育神经毒性。然而，成年后期和衰老过程中的神经毒性影响相对未知。本研究使用斑马鱼（ZF）作为模型，检查了一种 OP 化合物敌敌畏（DZN），以确定其神经行为后果，以及宏观（整个生物体基础呼吸）和微观（整个器官线粒体呼吸）的线粒体功能障碍。一组 14 个月大的成年 ZF 作为成年动物急性暴露（0.4、1.25 和 4.0 μM）五天，并作为成年动物进行测试，另一组在胚胎发育 5-120 小时后暴露（70、210 和 700 nM），并在幼虫、青少年、成年和衰老阶段进行测试。急性暴露的成年 ZF 没有表现出许多显著的神经行为影响或线粒体功能障碍。相反，胚胎期暴露的 ZF 在生命的每个阶段都表现出改变的行为功能，这些功能随着鱼从一个发育阶段过渡到下一个发育阶段而出现和减弱。发育期间 DZN 暴露的 ZF 的线粒体耗氧量测量结果显示，大脑和睾丸等器官的低剂量和中剂量组显著增加。总体而言，有迹象表明，早期发育暴露于 DZN 会在整个成年期和衰老期继续对其神经行为和细胞产生不利影响。
