Understanding the central embryonic vasopressin system

项目摘要 令人信服的证据表明，中央胚胎加压素系统在性别特异性 大脑发育和随后的行为。加压素系统存在，并在 胚胎发育中，配体的表达存在性别差异。然而， 这个系统的结构和功能因此，R15提案的工作假设是， 中枢胚胎加压素系统，特别是加压素1a受体信号传导， 支持女性和男性社会行为的神经回路的发展。为了验证这一 假设提出了三个具体目标。第一个目标是确定发展中国家的结构细节， 雌性和雄性的加压素系统。第二个目标是确定胚胎加压素 受体信号传导影响女性和男性大脑发育。第三个目标是建立一个萌芽状态， 加压素受体信号传导对社会行为具有性别特异性影响。拟议的研究是 科学上很重要，因为了解胚胎加压素系统如何影响性别特异性 老鼠的大脑发育和社会行为对人类也有影响。具体来说，几个 具有神经发育起源的神经精神疾病，其中许多具有已知的性别偏见 对男性，与社会行为的损害有关，这些行为与加压素有关。 系统因此，从拟议的实验中产生的数据将提供对一些问题的重要见解。 这些疾病的共同起源，并将使我们更接近更有针对性的干预措施。

PROJECT SUMMARY Compelling evidence suggests that the central embryonic vasopressin system has a role to play in sex-specific brain development and subsequent behavior. The vasopressin system is present and functional during embryonic development, with sex differences in the expression of the ligand. However, very little is known about the structure or function of this system. Thus, the working hypothesis of this R15 proposal is that the central embryonic vasopressin system, and specifically vasopressin 1a receptor signaling, directly contributes to the development of the neural circuitry that supports social behavior in females and males. To test this hypothesis three specific aims are proposed. The first aim will define the structural details of the developing vasopressin system in females and males. The second aim will determine how embryonic vasopressin receptor signaling impacts female and male brain development. The third aim will establish that embryonic vasopressin receptor signaling has sex-specific effects on social behavior. The proposed research is scientifically important because understanding how the embryonic vasopressin system affects sex-specific brain development and social behavior in mice has implications for humans. Specifically, several neuropsychiatric disorders with neurodevelopmental origins, many of which have a known sex-bias skewed towards males, are associated with impairments in social behaviors that have been linked to the vasopressin system. Thus, the data generated from the proposed experiments will provide critical insights into some of the shared origins of these disorders and will move us closer to more targeted interventions.