Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Shiwa-gun, Iwate 028-3694, Japan.
Physiol Behav. 2010 Sep 1;101(2):297-301. doi: 10.1016/j.physbeh.2010.05.015. Epub 2010 Jun 1.
Thyroid hormones play important roles in vertebrate brain development. However, there is little understanding of the direct effects of fetal thyroid dysfunction, i.e., not acquired through the mother, on learning ability. In the present study, we use a chick embryo as a fetal model to investigate the effects of prenatal exposure to antithyroid drugs on imprinting behavior in hatched chicks. Methimazole (MMI) at 20micromol/egg or 5micromol/egg of propylthiouracil (PTU) was administered to eggs on day 14 while the control was given only a vehicle. An imprinting test was conducted after the chicks hatched. Day-old chicks were exposed to a rotating training object for 150min. The next day, the trained chicks were exposed to the training object and a novel object. The imprinting preference was represented as a preference score (PS) calculated as the rate of following the training object to following the training and novel objects. In the MMI-treated chicks, the PS was 0.68+/-0.06 (range, 0.38-0.88), which was significantly lower than that in the control chicks (0.86+/-0.04, p<0.01). In the PTU-treated chicks, the PS was 0.69+/-0.04 (range, 0.52-0.89), which was also significantly lower than that in the control (0.88+/-0.02, p<0.001). The present findings suggested that fetal thyroid dysfunction inhibited brain development, leading to impaired learning and memory. Our chick model can be considered useful for investigating the direct effects of prenatal exposure to antithyroid drugs or substances in the environment on learning ability after birth.
甲状腺激素在脊椎动物大脑发育中发挥着重要作用。然而,对于胎儿甲状腺功能障碍(即不是通过母体获得的)对学习能力的直接影响,人们知之甚少。在本研究中,我们使用鸡胚作为胎儿模型,研究产前暴露于抗甲状腺药物对孵化小鸡印迹行为的影响。在第 14 天,将甲巯咪唑(MMI)20μmol/卵或 5μmol/卵丙基硫氧嘧啶(PTU)施用于卵中,而对照组仅给予载体。在小鸡孵化后进行印迹测试。 1 日龄小鸡暴露于旋转训练物体 150min。第二天,经过训练的小鸡暴露于训练物体和新物体。印迹偏好表示为偏好得分(PS),通过跟随训练物体的比率来计算跟随训练和新物体的比率。在 MMI 处理的小鸡中,PS 为 0.68+/-0.06(范围,0.38-0.88),显著低于对照组小鸡(0.86+/-0.04,p<0.01)。在 PTU 处理的小鸡中,PS 为 0.69+/-0.04(范围,0.52-0.89),也显著低于对照组(0.88+/-0.02,p<0.001)。本研究结果表明,胎儿甲状腺功能障碍抑制大脑发育,导致学习和记忆受损。我们的小鸡模型可被认为对研究产前暴露于抗甲状腺药物或环境物质对出生后学习能力的直接影响有用。