Serotonin, CAM Expression and Toxins During Development

描述：（由申请人提供）：暴露于以下物质后的行为缺陷 不同的神经毒物在发展过程中可能表现为延迟， 一个行为的开始，一个先前表达的行为的回归， 在发育早期（正常发病或发育之前）观察到的表现 行为），或不寻常或异常行为的侵入， 这些行为通常在发育时间点出现。这些行为 这些缺陷都出现在自闭症儿童的临床病例中， 广泛性发育障碍，可能是出生后晚期或早期 新生儿暴露于神经毒物。当前研究项目的目标 包括a）表征与小脑相关行为的正常发育， 纹状体和海马发育通过行为测试和变化， 细胞粘附分子（CAM）; B）给予甲基汞和钠 丙戊酸盐给药于动物的正常个体发育之前或之后， 行为，以确定大脑发育的关键时期， 这些化合物影响; c）将这些细胞的正常和异常发育联系起来， 行为区域变化神经化学以及CAM的改变 水平和CAM mRNA在离散的脑区，以及评估 这些化合物的神经毒性潜力，使用独立的试验 根据细胞粘附蛋白的变化，d）评估治疗动物的敏感性 以便以后用可能潜在地加剧缺陷的试剂进行挑战， 在行为上产生干扰，或减轻功能缺陷和逆转 改变细胞粘附分子表达。

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.