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

环境中常见的化学物质有可能破坏性腺激素在生殖过程中的作用。 人类发展例子包括广泛使用的化学品双酚A，这是雌激素，和 邻苯二甲酸盐，这是抗雄激素。这两种化学物质都是这个形成中心提案的重点。 除了对生殖功能的潜在影响外，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 初步和有限的范围和预算内，将首先模拟只有双酚A的影响， hooded大鼠，一种动物模型，其中大脑皮层的性别差异已被记录， 已知在围产期和青春期受激素环境的影响。 双酚A对神经元数量的影响，一个非常基本的功能构建块，将在两个 大鼠的皮质区，视觉皮层和内侧前额叶皮层（PL和IL），其中性别差异 已经被找到了。单独的动物组将暴露于0、4、40或400| jg/kg/天。当大鼠成年后，将用体视学方法定量每个皮质区域中的神经元数量。除了神经元数量上的性别差异外，这些皮层区域在行为中发挥的作用类似于项目1和项目2中评估的人类婴儿和青少年的行为。 皮质改变的行为后果也将在视觉空间任务中进行研究，即径向臂迷宫，该任务在几个实验室中始终显示出性别差异。作为成年大鼠，所有大鼠将在17臂放射状迷宫中进行测试，其中有诱饵和无诱饵臂，以便可以测试参考记忆和工作记忆。在动物体内，将进行行为表现和神经元数量之间的比较。

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 |jg/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.