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Synthetic Progestin Exposure & Mesocortical Dopamine System Development

合成孕激素暴露

基本信息

批准号：
8788421
负责人：
CHRISTINE K WAGNER
金额：
$ 22万
依托单位：
STATE UNIVERSITY OF NEW YORK AT ALBANY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8788421
关键词：
17p ARHGEF5 gene Adolescence Adolescent Adult Animals Attention Attention deficit hyperactivity disorder Behavior Behavioral Behavioral inhibition Benefits and Risks Brain Cell Count Cells Child Clinical Cognitive Complex Data Development Dopamine Dopaminergic Cell Elderly Exposure to Female Fiber Growth Health High Pressure Liquid Chromatography Human Hydroxyprogesterone Caproate Impulsivity Incidence Infant Knowledge Laboratory Rat Learning Disabilities Life Light Longevity Mass Spectrum Analysis Medial Mediating Memory Midbrain structure Modeling Mothers Nature Neonatology Nuclear Outcome Pathway interactions Performance Perinatal Perinatal Exposure Pharmaceutical Preparations Pilot Projects Placenta Plasma Play Prefrontal Cortex Pregnancy Pregnant Women Premature Birth Premature Infant Prevention Progesterone Progesterone Receptors Progestins Psyche structure Rattus Risk Rodent Model Role Short-Term Memory Synthetic Progestogens Systems Development Testing Time Tyrosine 3-Monooxygenase Ventral Tegmental Area Woman cognitive development cognitive task density dopamine system fetal flexibility frontal lobe in utero innovation male nerve supply neural circuit neurochemistry neurodevelopment neuronal cell body novel object recognition peer postnatal prevent receptor receptor function research study steroid hormone

项目摘要

DESCRIPTION (provided by applicant): The administration of synthetic progestins to pregnant women for the prevention of premature delivery has increased dramatically in recent years. Despite this increase, very little is known about the potential effects of synthetic progestins on the developing brain. Preliminary data from rodent models suggest that progestins may play a role in the development of frontal cortex and the mesocortical dopamine system, a neurochemical pathway implicated in Attention Deficit Hyperactivity Disorder (ADHD). The objective of this proposal is to examine the effects of exposure to the synthetic progestin, 17¿-hydroxyprogesterone caproate in the development of the mesocortical dopamine pathway and subsequent complex cognitive behaviors using a rodent model. Aim 1 will test the hypothesis that exposure to 17P during development will alter the number of dopaminergic cells in the midbrain ventral tegmental area and will alter the density of dopaminergic fibers within the medial prefrontal cortex. Aim 2 will test the hypothesis exposure to 17P during postnatal life will alter working memory (Novel Object Recognition), behavioral inhibition/impulsivity (Inhibitory Avoidance Task) and cognitive flexibility (Set Shift Task). Results from these animal studies would vastly increase our knowledge about the potential effects of progestin exposure to generate specific hypotheses for future research regarding outcomes in children exposed in utero.

描述(由申请人提供)：近年来，为预防早产而给孕妇服用合成孕激素的情况急剧增加。尽管有这种增加，但人们对合成孕激素对发育中的大脑的潜在影响知之甚少。来自啮齿动物模型的初步数据表明，孕激素可能在额叶皮质和中皮质多巴胺系统的发育中发挥作用，这是一种与注意缺陷多动障碍(ADHD)有关的神经化学途径。这项建议的目的是利用啮齿动物模型研究合成孕激素17-羟孕酮己酸酯在中皮质多巴胺途径和随后复杂认知行为发展中的影响。目的1验证发育过程中暴露于17P会改变中脑腹侧被盖区多巴胺能细胞数量和改变内侧前额叶皮质多巴胺能纤维密度的假说。目标2将检验假设，在出生后生活中暴露于17P将改变工作记忆(新物体识别)、行为抑制/冲动(抑制回避任务)和认知灵活性(设置转移任务)。这些动物研究的结果将极大地增加我们对孕激素暴露的潜在影响的了解，从而为未来关于子宫内暴露的儿童结局的研究产生具体的假设。