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Prenatal alcohol/cannabinoid co-exposures and fetal brain development

产前酒精/大麻素共同暴露与胎儿大脑发育

基本信息

批准号：
10827625
负责人：
Kirill V Larin
金额：
$ 5.83万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10827625
关键词：
3-Dimensional Acute Address Adolescent Adult Age Alcohol consumption Alcohols Anatomy Angiogenesis Inhibition Behavior Behavioral Behavioral Assay Biological Assay Birth Blood Vessels Blood flow Brain Cannabinoids Cells Cerebrovascular Circulation Consumption Data Defect Development Developmental Disabilities Dose Drug usage Ethanol Exposure to Fetal Alcohol Exposure Fetal Development Fetal alcohol effects Fetus Goals Growth Histologic Human Hyperactivity Impairment Ingestion Intervention Intoxication Label Legal Light Literature Maternal Exposure Mediating Microscopy Modeling Molecular Molecular Analysis Mus Neurodevelopmental Disability Optical Coherence Tomography Outcome Outcome Study Pharmaceutical Preparations Placenta Positioning Attribute Pregnancy Outcome Public Policy Publishing Receptor Activation Recreation Reporter Reporting Research Resolution Risk Risk Taking Rodent Second Pregnancy Trimester Severities Signal Pathway Signal Transduction Teratogens Testing Ultrasonography United States National Institutes of Health Zebrafish addiction alcohol exposure angiogenesis behavioral outcome blood vessel development brain based brain size cannabinoid receptor cannabinoid receptor antagonist child bearing conditioned place preference craniofacial disability efficacy evaluation fetal in vivo indexing infant outcome innovation malformation marijuana legalization marijuana use mouse model multiple drug use nerve stem cell neural neurogenesis neurovascular novel offspring optical imaging pharmacologic polysubstance use preference prenatal prevent protective effect psychologic synergism synthetic cannabinoid trend vasculogenesis virtual young adult

项目摘要

Prenatal alcohol exposure (PAE) is an established cause of brain-based disability, though co- exposure to other drugs, i.e., poly-substance use, can exacerbate adverse PAE-associated infant outcomes. The practice of Simultaneous Alcohol and Cannabinoid (SAC) use, i.e., co- ingestion, is an emerging trend among adolescents and adults of child-bearing age. SAC is motivated and maintained because combined use of alcohol and cannabinoids amplifies each drug’s psychological effect. Cannabinoids are known contributors to teratogenicity. However, we know virtually nothing about potential consequences of SAC for birth outcomes. The premise of the proposed studies is informed by the published literature, which indicates that PAE effects are, in part, mediated by activation of cannabinoid receptor signaling pathways and that PAE and prenatal cannabinoids engender similar fetal developmental outcomes. Moreover, recently published data shows developmental synergy between sub-teratogenic doses of cannabinoids and ethanol in non-mammalian vertebrate models. Based on these, as well as our own preliminary data we plan to address two questions: Firstly, “is SAC more damaging to fetal development than either alcohol or cannabinoids alone?”; Secondly, and importantly, “will cannabinoid antagonists protect against effects of PAE & SAC?”. Our studies will focus on the effects of SAC on neurogenesis and vasculogenesis, the complementary growth of vasculature that supports fetal brain growth. We plan to use in vivo and ex vivo mouse PAE models in combination with molecular assays and behavioral assays for hyperactivity and conditioned place preference, as well as state-of-the-art optical imaging (optical coherence tomography and light-sheet microscopy) and high-resolution ultrasound imaging, to assess the effects of SAC on, (Aim #1) brain and behavior, and (Aim #2) on vasculogenesis and cerebrovascular blood flow. Our overarching goal, to identify and minimize the contribution of factors, including poly-drug use, that contribute to increased risk for brain disabilities due to PAE, is consistent with the goals of the Collaborative Research on Addiction at NIH (CRAN) initiative. The rapid spread of recreational cannabis use means that SAC is an important emerging mode of drug consumption, and a potential contributor to the severity of PAE effects. As an outcome of these studies, we will acquire evidence to guide human studies on SAC birth outcomes, and to assess the efficacy of novel pharmacological intervention strategies targeted to cannabinoid receptors as a means to prevent or reverse effects of PAE.

产前酒精暴露（PAE）是一种确定的脑残疾原因，尽管有共同的原因