Roegge Cindy S, Wang Victor C, Powers Brian E, Klintsova Anna Y, Villareal Sherilyn, Greenough William T, Schantz Susan L
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Toxicol Sci. 2004 Feb;77(2):315-24. doi: 10.1093/toxsci/kfg252. Epub 2003 Nov 4.
Epidemiological and laboratory studies indicate that polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) may have additive or interactive adverse effects on nervous system function. Prior studies have shown that high doses of MeHg target the cerebellum and impair balance and coordination, but the effects of PCBs on cerebellar function were unknown. In addition, the combined effects of PCBs and MeHg on cerebellar function have not been studied previously. Therefore, we investigated the effects of developmental exposure to PCBs, MeHg, or PCBs + MeHg on three motor tasks that involve cerebellar functions. Female Long-Evans rats were exposed to MeHg (0.5 ppm in drinking water), PCBs (6-mg/kg/d Aroclor 1254), PCBs + MeHg, or vehicle only beginning 4 weeks prior to breeding, through pregnancy, and continuing through postnatal day (PND) 16. Starting at approximately PND 60, one male and one female from each litter were tested on three motor tasks that involve cerebellar function. PCB + MeHg-exposed rats were impaired relative to the controls on a task requiring them to traverse a rotating rod. Rats exposed to PCBs alone were also somewhat impaired relative to the controls, whereas MeHg-exposed rats were not significantly different from the controls. There were no statistically significant deficits related to PCB or MeHg exposure on a vertical rope-climbing test or a parallel bar test. Our results demonstrate that the possibility of additive neurotoxic effects of PCBs and MeHg needs to be seriously considered.
流行病学和实验室研究表明，多氯联苯（PCBs）和甲基汞（MeHg）可能对神经系统功能产生相加或相互作用的不良影响。先前的研究表明，高剂量的甲基汞会靶向小脑并损害平衡和协调能力，但多氯联苯对小脑功能的影响尚不清楚。此外，多氯联苯和甲基汞对小脑功能的联合影响此前尚未得到研究。因此，我们研究了发育期暴露于多氯联苯、甲基汞或多氯联苯+甲基汞对三项涉及小脑功能的运动任务的影响。雌性Long-Evans大鼠从交配前4周开始，经怀孕期，直至出生后第16天（PND 16），暴露于甲基汞（饮用水中0.5 ppm）、多氯联苯（6 mg/kg/d Aroclor 1254）、多氯联苯+甲基汞或仅暴露于溶剂。从大约出生后第60天开始，对每一窝中的一只雄性和一只雌性大鼠进行三项涉及小脑功能的运动任务测试。在一项要求它们穿过旋转杆的任务中，暴露于多氯联苯+甲基汞的大鼠相对于对照组表现受损。单独暴露于多氯联苯的大鼠相对于对照组也有一定程度的受损，而暴露于甲基汞的大鼠与对照组无显著差异。在垂直爬绳试验或双杠试验中，未发现与多氯联苯或甲基汞暴露相关的统计学显著缺陷。我们的结果表明，需要认真考虑多氯联苯和甲基汞产生相加神经毒性作用的可能性。
