Impact of Maternal Methamphetamine Abuse on Neonatal Immunity

母亲滥用甲基苯丙胺对新生儿免疫力的影响

• 批准号: 8045879
• 负责人: Luis R Martinez
• 金额: $ 11.97万
• 依托单位: LONG ISLAND UNIVERSITY C. W. POST CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8045879
• 关键词: Adult; Affect; Award; Behavior; Blood - brain barrier anatomy; Candida albicans; Cells; Central Nervous System Infections; Central Nervous System Stimulants; Cognitive; Communicable Diseases; Cryptococcus neoformans; Defect; Development; Drug abuse; Drug usage; Exposure to; Female of child bearing age; Fetus; Foundations; Future; Goals; Immune; Immune system; Immunity; Investigation; Knowledge; Methamphetamine; Molecular; Mothers; Mus; Natural Immunity; Neonatal; Neuraxis; Pathway interactions; Pharmaceutical Preparations; Placenta; Population; Predisposition; Pregnancy; Pregnant Women; Public Health; Research; Risk; Role; Scourge; Societies; design; drug of abuse; fetal methamphetamine exposure; fungus; high risk; in utero; in vivo Model; innate immune function; maternal methamphetamine abuse; maternal methamphetamine use; methamphetamine abuse; microbial; mouse model; neonate; offspring; pathogen; prenatal exposure; programs; response; tissue culture

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.

描述（由申请人提供）：甲基苯丙胺（甲基苯丙胺）是美国和世界上滥用的主要药物。此外，在潜在的短期和长期风险上，女性对育龄的女性滥用育龄已成为公共卫生的重大关注。在怀孕中，甲基苯丙胺可以越过胎盘并到达胎儿。我的计划旨在在我们了解新生儿的先天免疫系统如何受到母体甲基甲基甲基苯酚在分子和细胞水平上影响的主要进步。尽管在怀孕期间暴露于该药物的后代中甲基甲基苯丙胺引起的身体和认知缺陷有大量信息，但缺乏关于其对先天免疫的影响的知识。我先前已经表明，METH会改变成年宿主有效应对微生物挑战的能力，并假设在子宫内暴露于Meth的新生儿将在先天免疫方面进一步缺陷。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具有有缺陷的先天免疫力； （2）评估甲基对微生物挑战的暴露新生儿BBB完整性的影响。我认为该项目在免疫，宿主 - 病原体相互作用和药物滥用领域具有相当大的意义。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，以应对我们社会的祸害。甲基苯丙胺是我们社会的主要祸害。该药物不利地改变了人们的行为，包括使用户处于收购多种传染病的高风险。不幸的是，孕妇使用甲基苯丙胺组成了重要的人群。关于药物使用对滥用甲基苯丙胺的后代的影响的信息很少。使用小鼠滥用模型，我的程序将定义母体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液屏障的细胞。