Hormonal Contraceptives and Adolescent Brain Development

激素避孕药和青少年大脑发育

• 批准号: 10668018
• 负责人: BENEDETTA J LEUNER
• 金额: $ 22.72万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668018
• 关键词: Acne; Address; Adolescence; Adolescent; Adrenal Cortex Hormones; Adult; Antidepressive Agents; Behavior; Behavioral; Blood; Brain; Brain region; Cells; Cognitive; Contraceptive Agents; Contraceptive Usage; Corticosterone; DLG4 gene; Data; Development; Dysmenorrhea; Elements; Endocrine; Estradiol; Ethinyl Estradiol/Levonorgestrel; Exposure to; Feedback; Female; Female Adolescents; Glucocorticoids; Goals; Gonadal Steroid Hormones; Hormonal; Hormones; Human; Hydrocortisone; Immune; Impairment; Individual; Knowledge; Lead; Link; Longevity; Major Depressive Disorder; Medial; Mediating; Mental Depression; Microglia; Modification; Moods; Neurons; Neurosecretory Systems; Ovarian hormone; Peripheral; Persons; Phagocytosis; Pharmacologic Substance; Play; Prefrontal Cortex; Process; Progesterone; Puberty; Rattus; Regulation; Reporting; Research; Risk; Rodent; Role; Shapes; Stress and Coping; Structure; Synapses; Teenagers; Testing; Time; United States; Woman; Women' s Health; adolescent brain development; aged; analog; behavioral health; behavioral outcome; brain health; clinical effect; critical developmental period; critical period; experimental study; flexibility; hormonal contraception; hypothalamic pituitary gonadal axis; hypothalamic-pituitary-adrenal axis; innovation; interest; neurodevelopment; neurosteroids; receptor expression; response; sex; sexually active; steroid hormone; steroid hormone receptor; suicidal risk; synaptic pruning

PROJECT SUMMARY Hormonal contraceptives (HC) are used by 10 million people in the United States alone. While HC have played an important role in revolutionizing women’s health, the impact of HC on the brain have not been well studied, especially during adolescence when HC use often begins. There is a critical need for this knowledge as a growing number of recent studies suggest that use of HC, specifically among adolescents, is associated with subsequent antidepressant use, greater likelihood of developing depression, and increased suicide risk. Adolescence is a critical period of hormone-mediated brain development. Among the brain regions with the most significant maturational changes during adolescence is the prefrontal cortex (PFC), or medial prefrontal cortex (mPFC) in rodents. Because of the extended period of PFC/mPFC development and its well-known role in depression, our central hypothesis is that adolescent exposure to contraceptive hormones may exacerbate the risk for mood dysregulation by perturbing normal PFC development. We will employ daily administration of hormones commonly used in HC (ethinyl estradiol and levonorgestrel) to adolescent rats and examine interrelated endocrine, brain, and behavioral endpoints of relevance to the mPFC. Particular domains of interest in these studies include central steroid hormone levels and receptor expression (Aim 1), synaptic pruning and microglia-synaptic interactions (Aim 2), and long-term programming of behavioral outcomes dependent on mPFC, including stress coping and cognitive flexibility (Aim 3). The research proposed in this application is innovative because it investigates a widely used pharmaceutical for which there is little known about its effects on the brain during an important time of the female lifespan when the potential to shape the trajectory of neural development is high. The proposed research is significant because it is expected to generate knowledge about the effects of adolescent HC use on the female PFC. Ultimately, neuroscientific studies on HC will advance women’s health research and are a much needed step in achieving our long term goal of advancing knowledge of how sex specific factors influence the brain across the lifespan.

项目摘要 仅在美国，一千万人就会使用激素避孕药（HC）。 hc玩了 HC对大脑的影响在改变妇女健康方面的重要作用并不是很好的研究， 尤其是在HC使用时经常开始使用时。作为一个知识的迫切需要 越来越多的最近研究表明，HC，特别是在青少年中的使用，与 随后的抗抑郁药，抑郁症的可能性更大，自杀风险增加。 青少年是马介导的大脑发育的关键时期。在大脑区域中 青少年期间的显着成熟变化是前额叶皮层（PFC）或中位前额叶皮层 （MPFC）在啮齿动物中。由于PFC/MPFC开发的长期及其在 抑郁症，我们的核心假设是，青少年接触避孕恐怖可能会加剧 通过干扰正常的PFC发展，情绪失调的风险。我们将雇用日常管理 通常用于HC（乙基雌二醇和左甲虫）的术语至青少年大鼠并检查 与MPFC相关的相关内分泌，大脑和行为终点。特定的感兴趣领域 在这些研究中，包括中央类固醇水平和受体表达（AIM 1），突触修剪和 小胶质细胞突触相互作用（AIM 2）和行为结果的长期编程 MPFC，包括应力应对和认知灵活性（AIM 3）。该应用程序提出的研究是 创新性，因为它研究了一种广泛使用的药物，对其效果一无所知 在女性寿命的重要时期，在大脑上塑造中性轨迹的可能性 发展很高。拟议的研究很重要，因为它有望产生有关的知识 青少年HC使用对雌性PFC的影响。最终，对HC的神经科学研究将进步 妇女的健康研究是实现我们促进知识的长期目标的急需的一步 性别因素如何影响整个寿命的大脑。