Impact of Maternal Methamphetamine Abuse on Neonatal Immunity

简介（由申请人提供）：甲基苯丙胺（冰毒）是美国和世界上滥用的主要药物。此外，育龄女性滥用冰毒已成为一个重大的公共卫生问题，对暴露的胎儿有潜在的短期和长期风险。在怀孕期间，冰毒可以通过胎盘到达胎儿。我的项目旨在使我们对新生儿先天免疫系统如何在分子和细胞水平上受到母体滥用冰毒的影响的理解取得重大进展。虽然关于甲基苯丙胺对怀孕期间接触甲基苯丙胺的后代造成的身体和认知缺陷有大量信息，但关于甲基苯丙胺对先天免疫的影响却缺乏知识。我之前已经证明甲基安非他明会改变成年宿主有效应对微生物挑战的能力，我假设在子宫内暴露于甲基安非他明的新生儿会有进一步的先天免疫缺陷。提出了两个目的：(1)确定怀孕期间暴露于甲基苯丙胺的后代是否存在先天免疫缺陷；(2)评估甲基安非他明对新生儿血脑屏障完整性的影响，以应对微生物的挑战。我相信这个项目在免疫、宿主-病原体相互作用和药物滥用等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。这种药物对人们的行为产生了不利的影响，包括使使用者面临感染各种传染病的高风险。不幸的是，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母亲的后代的影响的资料很少。通过滥用小鼠模型，我的项目将确定母体使用甲基苯丙胺对先天免疫系统特定细胞功能的影响，以及构成新生儿血脑屏障的细胞。

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.