Estradiol and Glutamate in the Developing Hypothalamus

发育中的下丘脑中的雌二醇和谷氨酸

• 批准号: 7275668
• 负责人: Jaclyn Marie Schwarz
• 金额: $ 3.07万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-14 至 2008-09-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275668
• 关键词: Autistic Disorder; Behavior; Brain; Characteristics; Data; Dendritic Spines; Development; Disease; Estradiol; Excitatory Synapse; Exhibits; Female; Glutamates; Goals; Hypothalamic structure; Medial; Mental disorders; Mood Disorders; N-Methyl-D-Aspartate Receptors; Neurologic; Newborn Infant; Pattern; Physiology; Prevalence; Process; Rodent; Role; Schizophrenia; Sex Behavior; Sex Bias; Sex Characteristics; Site; Testosterone; Thinking; Work; base; brain behavior; male; neurochemistry; novel; sex

DESCRIPTION (provided by applicant): Male and female brains exhibit fundamental morphological differences thought to underlie sex differences in physiology and behavior. Development of the male rodent brain includes the completion of two distinct processes: masculinization and defeminization. In the rodent, estradiol initiates both processes during a restricted sensitive period. During development and adulthood, the medial basal hypothalamus (MBH) is a key target for estradiol. The MBH is important for female sex behavior and a possible site of defeminization in the male brain. Dendritic spines are the major sites of excitatory synapses. In the MBH, newborn males have more dendritic spines than females and treatment of females with testosterone, which is aromatized to estradiol, increases dendritic spines in this region to levels seen in males. Recent work has begun to investigate the mechanism of masculinization. However, little is known about the mechanism by which estradiol induces defeminization and establishes sexually dimorphic patterning in the MBH. Based on preliminary data and previous findings, we propose a novel role for glutamate release and the NMDA receptor in the process of defeminization of the brain and behavior. The goal of this proposal is to elucidate the mechanism by which estradiol induces defeminization of the rodent brain, to increase understanding of sex differences in brain development. Many neurological and psychiatric disorders including autism, affective disorder and schizophrenia exhibit a sex-biased prevalence and/or characteristics. These diseases are frequently disorders of neurochemicals or wiring. Understanding how sex effects normal brain development is necessary to understand how it may develop abnormally in psychiatric disorders.

描述（由申请人提供）：男性和女性大脑表现出基本的形态差异，被认为是生理和行为方面性别差异的基础。雄性啮齿动物大脑的发育包括完成两个不同的过程：男性化和非女性化。在啮齿动物中，雌二醇在有限的敏感期内启动这两个过程。在发育和成年期间，内侧基底下丘脑 (MBH) 是雌二醇的关键目标。 MBH 对于女性性行为很重要，也是男性大脑中女性化的可能部位。树突棘是兴奋性突触的主要部位。在MBH中，新生男性比女性有更多的树突棘，并且用睾酮（芳香化为雌二醇）治疗女性，可以使该区域的树突棘增加到男性的水平。最近的工作已经开始研究男性化的机制。然而，人们对雌二醇诱导去女性化并在 MBH 中建立性别二态性模式的机制知之甚少。根据初步数据和之前的发现，我们提出了谷氨酸释放和 NMDA 受体在大脑和行为去女性化过程中的新作用。该提案的目的是阐明雌二醇诱导啮齿动物大脑去女性化的机制，以增进对大脑发育性别差异的理解。许多神经和精神疾病，包括自闭症、情感障碍和精神分裂症，都表现出性别偏见的患病率和/或特征。这些疾病通常是神经化学物质或线路紊乱。了解性如何影响正常的大脑发育对于理解精神疾病中大脑如何异常发育是必要的。