Impact of Maternal Methamphetamine Abuse on Neonatal Immunity

描述（由申请人提供）：甲基苯丙胺（METH）是美国和世界上主要的滥用药物。此外，育龄妇女滥用甲基苯丙胺已成为一个重大的公共健康问题，因为它对接触甲基苯丙胺的胎儿可能造成短期和长期风险。在怀孕期间，METH可以穿过胎盘到达胎儿。我的计划是为了使我们的理解新生儿的先天免疫系统是如何在分子和细胞水平上受到母亲滥用甲基苯丙胺的影响的重大进展。虽然有大量的信息在怀孕期间暴露于药物的后代的METH引起的身体和认知缺陷，但缺乏关于其对先天免疫的影响的知识。我以前已经表明，甲基改变了成年宿主有效应对微生物挑战的能力，我假设新生儿在子宫内暴露于甲基将有进一步的先天免疫缺陷。提出了两个AIMS：（1）确定妊娠期间暴露于METH的后代是否具有先天免疫缺陷;（2）评估METH对暴露新生儿BBB完整性的影响，以应对微生物挑战。我相信这个项目在免疫、宿主-病原体相互作用和药物滥用领域具有相当重要的意义。我预计，了解这些领域之间的关系可能有助于制定更有效的公共卫生战略，以应对我们社会的这一祸害。甲基苯丙胺是我们社会的一大祸害。这种药物会对人们的行为产生不利影响，包括使使用者面临感染各种传染病的高风险。令人遗憾的是，孕妇是使用甲基苯丙胺的重要人群。关于吸毒对滥用甲基苯丙胺的母亲的后代的影响的资料很少。使用滥用小鼠模型，我的计划将定义母体甲基苯丙胺使用对先天免疫系统特定细胞和新生儿血脑屏障细胞功能的影响。

DESCRIPTION (provided by applicant): Methamphetamine (METH) is a major drug of abuse in the USA and the world. Furthermore, METH abuse by females of child-bearing age has become a significant public health concern in terms of potential short and long-term risks to an exposed fetus. In pregnancy, METH can cross the placenta and reach the fetus. My program is designed to make major advances in our understanding of how the innate immune system of neonates is affected at the molecular and cellular levels by maternal METH abuse. Although there is substantial information on the physical and cognitive defects caused by METH in offspring exposed to the drug during pregnancy there is a dearth of knowledge regarding its impact on innate immunity. I have previously shown that METH alters the capacity of the adult host to effectively respond to microbial challenges and I hypothesize that neonates exposed to METH in utero will have further defects in innate immunity. There are two AIMS proposed: (1) to determine whether offspring exposed to METH during pregnancy have defective innate immunity; and (2) to assess the effect of METH on the integrity of the BBB of exposed neonates in response to microbial challenge. I believe this project is of considerable significance in the fields of immunity, host-pathogen interactions and drug abuse. I anticipate that understanding the relationship between these fields may help to develop more effective public health strategies to deal with this scourge on our society. Methamphetamine is a major scourge on our society. The drug adversely changes people's behavior, including putting users at high risk for the acquisition of diverse infectious diseases. Unfortunately, pregnant women comprise an important population using methamphetamine. There is very little information on the effects of the drug use on the offspring of methamphetamine abusing mothers. Using mouse models of abuse, my program will define the impact of maternal methamphetamine use on the function of specific cells of the innate immune system and the cells that comprise the blood brain barrier of neonates.