Serotonin, CAM Expression and Toxins During Development

描述：(申请人提供)：暴露于 不同的神经毒物在发育过程中可能表现为延缓 一种行为的开始，一种先前表达的行为的回归 在发育早期(在正常发病或发育之前)的表现 行为)，或不寻常或异常行为的侵入，以取代 这些行为通常出现在发育的时间点。这些行为 缺陷，这些缺陷都见于自闭症儿童的临床病例或 广泛性发育障碍，可能是出生后晚期或早期的结果 新生儿暴露在神经毒物中。当前研究项目的目标 包括a)表征与小脑有关行为的正常发展， 纹状体和海马体发育通过行为测试和变化 细胞黏附分子(CAM)；b)管理甲基汞和钠 丙戊酸刚好在这些个体发育之前或之后的动物 行为，以确定大脑发育的关键时期 这些化合物影响；c)联系这些细胞的正常和异常发育 行为对区域性变化、神经化学和CAM变化的影响 不同脑区的水平和细胞间黏附分子mRNA，以及评估 用一种独立的分析方法研究这些化合物的神经毒性潜力 根据细胞黏附蛋白的变化评估用药动物的敏感性 以后挑战可能会加剧赤字的代理人， 在行为上产生干扰，或缓解功能缺陷和逆转 改变细胞黏附分子的表达。

DESCRIPTION: (provided by applicant): Behavioral deficits following exposure to different neurotoxicants during development may be manifested as a delay in onset of a behavior, a regression of a previously articulated behavior to performance seen earlier in development (before the normal onset or development of the behavior), or intrusions of unusual or aberrant behaviors which replace those behaviors normally seen at developmental time points. These behavioral deficits, which are all seen in clinical cases of children with autism or pervasive developmental disorders, may be the result of late postnatal or early neonatal exposure to neurotoxicants. The aims of the current research project include a) characterize normal development of behaviors related to cerebella, striatal and hippocampal development through behavioral testing and changes in cell adhesion molecules (CAMs); b) administer methylmercury and sodium valproate to animals just prior or just following the normal ontogeny of these behaviors in order to determine critical periods of brain development which these compounds affect; c) link normal and aberrant development of these behaviors to regional changes neurochemistry as well as alterations in CAM levels and CAM mRNA in discrete brain areas, as well as assessing the neurotoxic potential of these compounds using an assay which is independent from changes in cell adhesion proteins d) assess sensitivity of treated animals to later challenge with agents which may potentially exacerbate deficits, produce intrusions in behavior, or alleviate functional deficits and reverse altered cell adhesion molecule expression.