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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 母亲吸烟与胎儿、婴儿和儿童的各种不良发育结局有关。仅在美国，每年就有大约100万名婴儿在产前暴露在香烟烟雾中！虽然母亲在孕期吸烟是导致低出生体重的一个有充分证据的危险因素，并伴随着婴儿/儿童发育的并发症，但产前吸烟暴露与出生后神经行为/认知损害之间的直接联系仍然没有明确的定义。该研究计划的全球目标是建立鼠与人的实验相关性，从机械上研究吸烟导致的神经/认知发育缺陷的神经解剖学、细胞和分子基础。由于海马体在神经/认知中起着跨物种的核心作用，特别是在涉及学习和记忆的信息处理中，最初的中心假说是，怀孕期间母亲吸烟干扰了海马体的细胞和分子个体发育，导致子代依赖海马体的学习和记忆发生改变。在这项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，在该模型中，发育阶段(孕期和出生后早期)吸入香烟烟雾模拟了人类怀孕期间母亲吸烟的情况。以下假设正在接受测试。假设1：在模拟人类孕期吸烟的小鼠模型中，发育期间吸烟暴露会导致神经行为异常，涉及海马体依赖的学习和记忆。假设2：在发育过程中暴露在烟草烟雾中会引起小鼠海马区正常细胞结构和神经发生的改变，而对小鼠胎儿/新生儿的生长没有伴随的影响。假设3：发育期间吸烟暴露会导致海马区，小鼠个体发育过程中神经元亚型特异性基因表达的改变，这些基因是神经元发育可塑性、学习和记忆的关键中介。

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.