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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。 本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/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。对发育中暴露于香烟烟雾或环境空气（妊娠期1-18天和出生后1-21天）的动物的视丘依赖性学习/记忆的功能（行为）缺陷进行初步检查，结果表明，这种香烟烟雾暴露影响神经发育，并导致空间学习和认知缺陷。 此外，发育中的香烟烟雾暴露导致这些动物的焦虑和抑郁样行为增加。虽然从我们的初步分析来看，暴露于香烟烟雾的发育后代的海马体的总体或细胞形态没有明显变化，但暴露动物的分离海马体的基因表达谱表明参与神经元信号传导、学习和记忆等的各种基因的表达发生了显著变化。具体目标#1中提出的海马依赖性行为功能评估和具体目标#2中提出的海马总体和细胞形态评估都计划在未来6个月内完成。这些研究的成功完成，沿着研究计划具体目标#3和#4中提出的研究，将有助于了解子宫内烟草烟雾暴露对婴儿和儿童神经/认知发育的影响及其机制，  长期  将有助于诊断和干预受产前母亲烟草滥用影响的儿童的学习障碍和其他认知障碍。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 present 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 neuro/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 central hypothesis under investigation is 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. Preliminary examination of functional (behavioral) deficits in hippocampus-dependent learning/memory in animals developmentally exposed (gestational day 1-18 and postnatal days 1-21) to cigarette smoke or ambient air demonstrated that such cigarette smoke exposure affects neurodevelopment and results in spatial learning and cognitive deficits. Moreover, developmental cigarette smoke exposure results in increased anxiety- and depression-like behavior the these animals. Although no alterations in the gross or cellular morphology of the hippocampus from developmentally cigarette smoke-exposed offspring are apparent from our preliminary analyses, gene expression profiling of the isolated hippocampus from the exposed animals indicates significant alterations in the expression of various genes involved in neuronal signaling, learning and memory, among others. Both the assessments of hippocampal dependent behavioral functions proposed in Specific Aim #1 and the assessments of hippocampal gross and cellular morphology proposed in Specific Aim #2 are targeted for completion in the coming 6 months. Successful completion of the these studies, along with those proposed in Specific Aims #3 and #4 of the Research Program will aid in understanding the effects of, and mechanisms underlying, in utero tobacco smoke exposure on neuro/cognitive development in infants and children, and  long-term  will facilitate the diagnosis of, and intervention into, learning disabilities and other cognitive impairments in children affected by prenatal maternal tobacco abuse.