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 仅在美国就有1000万人使用激素避孕药（HC）。当HC玩 HC在妇女健康革命中发挥着重要作用，但HC对大脑的影响尚未得到很好的研究， 特别是在青春期，经常开始使用HC。这方面的知识是一个关键的需要， 最近越来越多的研究表明，HC的使用，特别是在青少年中，与 随后使用抗抑郁药，更有可能发展为抑郁症，并增加自杀风险。 青春期是大脑发育的关键时期。在大脑中， 在青春期，一个重要的成熟变化是前额叶皮层（PFC），或内侧前额叶皮层 （mPFC）。由于全氟化学品/中间全氟化学品的开发时间较长， 抑郁症，我们的中心假设是，青少年接触避孕激素可能会加剧 通过干扰正常PFC发育而导致情绪失调的风险。我们将每天使用 HC中常用的激素（炔雌醇和左炔诺孕酮）给青春期大鼠， 与mPFC相关的相关内分泌、大脑和行为终点。感兴趣的特定领域 这些研究包括中枢类固醇激素水平和受体表达（Aim 1），突触修剪和 小胶质细胞-突触相互作用（Aim 2），以及依赖于 mPFC，包括压力应对和认知灵活性（目标3）。本申请中提出的研究是 创新，因为它研究了一种广泛使用的药物，但对其效果知之甚少 在女性生命的一个重要时期，当潜在的塑造神经的轨迹时， 发展很高。拟议的研究是重要的，因为它预计将产生知识， 青少年使用HC对女性PFC的影响。最终，对HC的神经科学研究将取得进展 妇女健康研究，是实现我们促进知识的长期目标所急需的一步。 性别因素如何影响整个生命周期的大脑。