Project 4: Effects of Bisphenol A (BPA) on the Developing Cortex

环境中的常见化学物质有可能扰乱性腺激素在 人的发展。例子包括广泛使用的化学物质双酚A，它是雌激素，以及 邻苯二甲酸酯，它是抗雄激素的。这两种化学物质都是这个形成性中心提案的重点。 除了生殖功能的潜在后果外，认知神经功能，也是 受性腺激素的影响，可能会被这些内分泌干扰物改变。目前的试点项目是 初步的，在其有限的范围和预算内，将初步模拟只有双酚A的影响 一种动物模型，在这种动物模型中，大脑皮层的性别差异已经被记录在案，并被 在围产期和青春期都会受到荷尔蒙环境的影响。 双酚A对神经元数量的影响，这是一种非常基本的功能构建块，将分两部分进行探讨 大鼠皮质、视觉皮质和内侧前额叶皮质(PL和IL)的性别差异 都被发现了。不同组的动物将在围产期每天暴露于0、4、40或400“亩”克/公斤/天或 青春期前后。当大鼠成年后，每个皮质区域的神经元数量将被量化。 用体视学的方法。除了它们在神经元数量上的性别差异外，这些大脑皮层 区域在行为方面的作用类似于人类对婴儿和青少年的评估 在项目1和2中。 大脑皮质改变的行为后果也将在视觉空间任务中进行调查， 放射臂迷宫，在几个实验室中一直显示性别差异。作为成年人，所有的老鼠都会 在17臂有诱饵和无诱饵臂的径向迷宫上进行测试，以便参考和工作 记忆力是可以测试的。在动物行为表现和神经元数量的比较中 都会被制造出来。

Common chemicals in the environment have the potential to disrupt the role of gonadal hormones during human development. Examples include the widely used chemicals bisphenol A, which is estrogenic, and the phthalates, which are anti-androgenic. Both chemicals are the focus of this formative center proposal. Besides the potential consequences for reproductive functions, cognitive neural functions, which are also influenced by gonadal hormones, may be altered by these endocrine disruptors. The present pilot project is preliminary and within its limited scope and budget, will initially model the effects of only bisphenol A in hooded rats, an animal model where sex differences in the cerebral cortex have been documented and are known to be influenced by hormonal milieu during both the perinatal and peripubertal period. The effects of bisphenol A on neuron number, a very basic building block of function, will be explored in two cortical areas of rats, the visual cortex and the medial prefrontal cortex (PL and IL) where sex differences have been found . Separate groups of animals will be exposed to 0, 4, 40 or 400 "mu"g/kg/day perinatally or peripubertally. When the rats reach adulthood, the number of neurons in each cortical area will be quantified with stereological methods. In addition to their established sex differences in neuron number, these cortical regions play a role in behaviors analogous to those that will be assessed in human infants and adolescents in Projects 1 and 2. The behavioral consequences of cortical alterations will also be investigated in a visual spatial task, the radial arm maze, which consistently shows sex differences in several laboratories. As adults, all rats will be tested on a 17-arm radial maze with both baited and unbaited arms so that both reference and working memory can be tested. Within animal comparisons between behavioral performance and neuron number will be made.