PRE- AND POSTNATAL TOBACCO SMOKE EXPOSURE:EFFECTS ON NEUROCOGNITIVE DEVELOPMENT

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 母亲吸烟与各种不良胎儿，婴儿和儿童发育结果有关。 仅在美国，每年就有大约100万婴儿在出生前暴露在香烟烟雾中！虽然母亲在怀孕期间吸烟是一个有据可查的低出生体重的危险因素，其伴随的并发症对婴儿/儿童的发展，产前吸烟暴露和出生后的神经行为/认知障碍之间的直接联系仍然不明确。 该研究计划的全球目标是建立小鼠-人类实验相关性，以机械地研究母体吸烟诱导的神经元/认知发育缺陷的神经解剖学，细胞和分子底物。因为海马体在大脑中  跨物种  在神经/认知方面，特别是在涉及学习和记忆的信息处理方面，正在调查的最初的中心假设是，母亲在怀孕期间吸烟干扰了海马体的细胞和分子个体发生，导致后代依赖海马体的学习和记忆发生改变。在本研究计划下进行的动物研究采用了在我们实验室建立的小鼠模型，其中发育（妊娠期和出生后早期）吸入暴露于香烟烟雾模拟人类母亲在怀孕期间吸烟。以下假设正在测试中。 假设#1：在模拟人类母亲怀孕期间吸烟的小鼠模型中，发育期间的烟草烟雾暴露导致神经行为异常，涉及海马依赖性学习和记忆。 假设#2：在发育过程中暴露于烟草烟雾引起小鼠海马中正常细胞结构和神经发生的改变，对小鼠胎儿/新生儿生长没有伴随影响。 假设#3：在发育过程中暴露于烟草烟雾导致海马神经元亚型特异性基因表达的改变，这些基因在小鼠个体发育过程中是神经元发育可塑性、学习和记忆的关键介质。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Maternal cigarette smoking has been associated with a variety of adverse fetal, infant, and childhood developmental outcomes. In the United States alone, approximately one million infants are exposed prenatally to cigarette smoke each year! Although maternal cigarette smoking during pregnancy is a well documented risk factor for low birth weight, with its attendant complications for infant/childhood development, a direct linkage between prenatal cigarette smoke exposure and postnatal neurobehavioral/cognitive impairment remains poorly defined. The global objective of the research program is to establish mouse-human experimental correlates to mechanistically investigate the neuroanatomical, cellular and molecular substrates underlying maternal cigarette smoking-induced defects in neuron/cognitive development. Since the hippocampus subserves a central role  across species  in neuro/cognition, especially in the information processing involved in learning and memory, the original central hypothesis under investigation was that maternal tobacco use during pregnancy interferes with the cellular and molecular ontogenesis of the hippocampus, resulting in altered hippocampus-dependent learning and memory in the offspring. The animal studies conducted under this research program employ a mouse model, established in our laboratory, in which developmental (gestational and early postnatal) inhalation exposure to cigarette smoke simulates human maternal smoking during pregnancy. The following hypotheses are being tested. Hypothesis #1: Tobacco smoke exposure during development, in a murine model simulating human maternal cigarette smoking during pregnancy, results in neurobehavioral abnormalities involving hippocampus-dependent learning and memory. Hypothesis #2: Alterations in the establishment of normal cytoarchitecture and neurogenesis in the murine hippocampus are elicited by exposure to tobacco smoke during development, in the absence of attendant effects on murine fetal/neonatal growth. Hypothesis #3: Tobacco smoke exposure during development results in hippocampal, neuronal subtype-specific alterations in the expression of genes during murine ontogenesis that are critical mediators of neuronal developmental plasticity, learning and memory.