PASSIVE SMOKING DURING PREGNANCY--COGNITIVE DEVELOPMENT

怀孕期间被动吸烟——认知发展

• 批准号: 2155116
• 负责人: Charles F. Mactutus
• 金额: $ 9.9万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2155116
• 关键词: GABA receptor; adrenergic receptor; autoradiography; cholinergic receptors; cognition disorders; developmental neurobiology; embryo /fetus toxicology; environmental toxicology; enzyme activity; gamma aminobutyrate; hippocampus; histology; laboratory rat; longitudinal animal study; neuroanatomy; passive smoking; postnatal growth disorder; pregnancy; synthetic enzyme

Active maternal smoking during pregnancy is associated with adverse health effects for the infant at birth and throughout childhood. Only recently, however, has it been appreciated that involuntary passive cigarette smoke exposure of the pregnant woman (via household or work environmental exposures) may also be associated with adverse effects on fetal health and development. The present proposal is unique in representing the first programmatic attempt, in an animal model, to investigate the long-term consequences of passive maternal smoking during pregnancy on the conceptus. Using reference cigarettes with established smoke constituents to create clinically relevant conditions of sidestream smoke, as well as biological monitoring of smoke exposures, this proposal offers the following hypothesis: Passive maternal smoking during pregnancy has adverse effects on the neurobehavioral development of the fetus (as manifest in cognitive dysfunction) and these effects are caused by structural and functional disruption of the hippocampus. The specific aims of the program are: 1) To establish the nature and extent of cognitive dysfunction which occurs in the offspring following passive maternal cigarette smoking during pregnancy. Cognitive processes in the rodent will be evaluated via complex spatial and non-spatial tasks known to be sensitive indicators of hippocampal pathology. These studies will identify dose-response functions, critical exposure periods, and dissociations of specific cognitive deficits from sensory or motor impairments. 2) To establish the nature and extent of the structural alterations in the hippocampus which occur following passive maternal smoking during pregnancy. Quantitative neuroanatomical measurements, synthetic enzyme activity, and receptor autoradiography will be utilized to determine the structural integrity of the hippocampus. The hippocampus mediates spatial information processing in rodents and is also known to be highly susceptible to irreversible cytotoxic damage by moderate hypoxic episodes of varied origin. 3) To determine the relationship between the integrity of the hippocampus and the cognitive dysfunction using pharmacological probes. The functional integrity of two extrinsic neural pathways that project to the hippocampus (cholinergic & noradrenergic) and one intrinsic transmitter system (GABAergic) will be probed using selected pharmacological agonists and antagonists with the aim of predictively modifying the rats' behavior in spatial learning tasks. The goals of the current proposal are to quantitatively define the relationship between passive maternal smoke exposure during pregnancy and cognitive development of the offspring, and to identify characterize the neurobiological mechanism(s) underlying this cognitive deficit.

母亲在怀孕期间吸烟与不良健康有关 对婴儿出生时和整个童年期的影响。 就在最近， 然而，人们是否认识到，非自愿被动吸烟 孕妇的暴露（通过家庭或工作环境 暴露）也可能与对胎儿健康的不利影响有关 发展。 本提案的独特之处在于代表了第一个 在动物模型中进行有计划的尝试，以调查长期 母亲在怀孕期间被动吸烟对胎儿的影响。 使用具有已确定烟雾成分的参考香烟来创建 侧流烟雾的临床相关条件以及生物 监测烟雾暴露，该提案提供以下内容 假设：母亲在怀孕期间被动吸烟会产生不利影响 对胎儿神经行为发育的影响（如认知方面所表现的） 功能障碍），这些影响是由结构和功能引起的 海马体的破坏。 该计划的具体目标是： 1) 确定认知功能障碍的性质和程度 发生在母亲被动吸烟后的后代中 怀孕。 啮齿动物的认知过程将通过复杂的评估 已知是敏感指标的空间和非空间任务 海马病理学。 这些研究将确定剂量反应 功能、关键暴露期和特定的解离 感觉或运动障碍引起的认知缺陷。 2) 确定结构改变的性质和程度 产妇被动吸烟后出现的海马体 怀孕。 定量神经解剖学测量，合成酶 活性和受体放射自显影将用于确定 海马体的结构完整性。 海马体调节空间 啮齿动物的信息处理也被认为是高度 中度缺氧容易造成不可逆的细胞毒性损伤 来源各不相同。 3）确定海马完整性的关系 和使用药理学探针的认知功能障碍。 功能性的 投射到海马体的两条外在神经通路的完整性 （胆碱能和去甲肾上腺素能）和一种内在递质系统 (GABAergic) 将使用选定的药理学激动剂进行探测 拮抗剂的目的是预测性地改变大鼠的行为 空间学习任务。 当前提案的目标是定量定义 孕期被动吸烟与母亲被动暴露之间的关系 后代的认知发展，并确定其特征 这种认知缺陷背后的神经生物学机制。