Toxicology Division, Research Center for Occupational and Environmental Toxicology, IRCCS Salvatore Maugeri Foundation, Institute of Pavia, Via Maugeri, 10, 27100 Pavia, Italy.
Arch Toxicol. 2011 Oct;85(10):1281-94. doi: 10.1007/s00204-011-0660-y. Epub 2011 Feb 18.
MeHg (0.5 mg/kg/day) and/or PCB153 (5 mg/kg/day) effects, administered orally to rat dams (GD7-PND21), were explored in PND21 and PND36 offspring brain in terms of density (Bmax) and affinity (Kd) of dopamine D1-like (D1-Rs) and D2-like receptors (D2-Rs), by saturation binding studies. D1-Rs decreased density in both cortex and striatum (15-30%) by MeHg and PCB153, either alone or combined, without additivity in PND21 males. Changes disappeared by PND36. In females, only MeHg caused a 15% Bmax decrease in striatum. D2-Rs enhanced density (23-50%) and reduced affinity in cortex to a similar extent by all treatments in both weanling and pubertal males. Affinity was also decreased in females by all types of exposure at both ages, while density was enhanced by PCB153 only in a delayed manner (PND36). No changes were detected in striatum. In MeHg and MeHg + PCB153 pup cortex, Hg concentrations ranged, on PND21, between 0.25 and 0.89 and 0.94-1.40 μg/g tissue, respectively, and were 5- to sixfold lower 2 weeks later. PCB153 levels, in PCB153 ± MeHg treated rats, were about 15 μg/g tissue (PND21) and 4-8 μg/g tissue (PND36). In striatum, the Hg and PCB153 concentrations were similar to those in cortex. Brain kinetics trend also applied to blood PCB153 or Hg levels. Perinatal exposure to MeHg and/or PCB153 affects D1- and D2-Rs in a gender-, time-, and brain area-dependent manner. Combined treatment does not exacerbate the neurochemical effects of the individual compounds.
孕期和哺乳期经口给予孕鼠（GD7-PND21）氯化甲基汞（0.5mg/kg/天）和/或多氯联苯 153（5mg/kg/天），研究其对仔鼠 PND21 和 PND36 脑多巴胺 D1 样（D1-Rs）和 D2 样受体（D2-Rs）的密度（Bmax）和亲和力（Kd）的影响，采用饱和结合研究。无论是单独给予还是联合给予，MeHg 和 PCB153 在雄性仔鼠的皮质和纹状体中均降低 D1-Rs 的密度（15-30%），但不存在相加作用。这种变化在 PND36 时消失。在雌性中，仅 MeHg 引起纹状体 Bmax 减少 15%。在断奶和青春期雄性中，所有处理均以相似程度增加 D2-Rs 的密度（23-50%）和降低亲和力。所有类型的暴露在两个年龄阶段均降低雌性的亲和力，而仅在 PND36 时 PCB153 增加密度。纹状体未检测到变化。在 MeHg 和 MeHg+PCB153 仔鼠皮质中，Hg 浓度分别在 PND21 时为 0.25-0.89 和 0.94-1.40μg/g 组织，而在 2 周后降低 5-6 倍。在 PCB153+MeHg 处理的大鼠中，PCB153 的水平约为 15μg/g 组织（PND21）和 4-8μg/g 组织（PND36）。纹状体中的 Hg 和 PCB153 浓度与皮质相似。脑动力学趋势也适用于血 PCB153 或 Hg 水平。围产期接触 MeHg 和/或 PCB153 以性别、时间和脑区依赖的方式影响 D1-和 D2-Rs。联合处理不会加剧各化合物的神经化学作用。
