Function and Molecular Phenotyping of Amygdala Kisspeptin Neurons

杏仁核 Kisspeptin 神经元的功能和分子表型

• 批准号: 9243923
• 负责人: Shannon Brooke Zoe Stephens
• 金额: $ 2.62万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243923
• 关键词: Ablation; Amenorrhea; Amygdaloid structure; Anovulation; Anxiety; Area; Attention; Autistic Disorder; Behavior; Behavioral; Behavioral Mechanisms; Binding; Brain; Brain region; Cell Nucleus; Cells; Discrimination; Disease; Emotions; Employee Strikes; Estradiol; Estrogen Receptor alpha; Estrus; Event; Female; Fertility; GNRH1 gene; Genes; Goals; Human; Hypothalamic structure; Impairment; Infertility; KISS1 gene; KISS1R gene; Kallmann Syndrome; Link; Mammals; Medial; Mediating; Membrane; Messenger RNA; Molecular; Mus; Mutation; National Research Service Awards; Neurons; Neuropeptide Gene; Neuropeptides; Neurotransmitters; Odors; Ovulation; Periodicity; Phenotype; Physiological; Play; Population; Preoptic Areas; Primates; Proteins; Receptor Gene; Regulation; Reproduction; Reproductive Behavior; Reproductive Endocrinology; Reproductive Physiology; Research; Role; Schizophrenia; Sex Behavior; Sex Characteristics; Sheep; Signal Transduction; Smell Perception; Social Behavior; Stress; Structure of nucleus infundibularis hypothalami; Techniques; Technology; Temporal Lobe; Time; Tracer; Transcript; Translating; Work; cell type; design; hypothalamic pituitary gonadal axis; improved; in vivo; infertility treatment; insight; male; molecular phenotype; novel; preference; public health relevance; receptor; reproductive; reproductive axis; reproductive function; reproductive hormone; reproductive neuroendocrinology; sex; social; transcriptome sequencing; virtual

 DESCRIPTION (provided by applicant): The neuropeptide kisspeptin, encoded by the Kiss1 gene, activates reproduction by signaling directly to GnRH neurons through the kisspeptin receptor (Kiss1r). Kiss1/kisspeptin cells are detected in several brain regions, primarily the hypothalamic anteroventral periventricular nucleus (preoptic area in primates and sheep), the hypothalamic arcuate nucleus, and the amygdala, but the regulation and function of kisspeptin in the amygdala has received very little attention. The medial amygdala (MeA) is an estradiol-sensitive region implicated in modulating reproductive endocrinology and behavior, but the mechanism(s) by which the MeA influences reproduction, and if these mechanisms are similar between males and females, remain unknown. In addition, the MeA is also important for the discrimination and modulation of olfactory information on aspects of reproductive physiology and behavior, with MeA neurons discriminating and selectively responding to opposite- sex odors. However, the identity of the specific MeA cell types involved and the mechanisms by which this occurs are still poorly understood. Given that kisspeptin treatment alters reproductive physiology and that kisspeptin signaling is required for opposite-sex odor preference, it is possible that kisspeptin neurons in the MeA play an important role in these specific reproductive events. The overall goal of this project is to examine the regulation and reproductive function of Kiss1 neurons in the MeA, of which virtually nothing is known at present. Aim 1 examines the neuroanatomical projections of MeA Kiss1 neurons to determine whether MeA Kiss1 neurons directly project to GnRH neurons, thus having the potential to directly influence reproduction, and whether MeA Kiss1 efferent projections are similar in males and females. Aim 2 directly examines the possibility for reproductive function of Kiss1 neurons in the MeA, as well as the influence of Kiss1 neurons in the MeA on opposite-sex odor preference. In addition, Aim 2 explores whether potential functions of Kiss1 neurons in the MeA are similar for males and females. Aim 3 will determine what genes are actively expressed by MeA Kiss1 neurons, whether this molecular phenotype is E2 dependent, and if the genes expressed by MeA Kiss1 neurons differ between males and females, all of which will provide novel and fundamental insight into the regulation and potential functions of these particular Kiss1 neurons. In addition o modulating reproduction, the MeA mediates various behaviors such as stress, anxiety, and social behavior, and the proposed research will not only determine the role of MeA Kiss1 neurons in regulating reproduction, but will also provide a basis to further explore potential non-reproductive functions of MeA Kiss1 neurons. Overall, this work may provide important information relevant to treatments in infertility, anovulation, amenorrhea, and idiopathic hypogonadotropic hypogonadism, as well as improve our understanding of reproductive physiology regulation in disorders associated with aberrant amygdala function.

 描述(申请人提供)：由Kiss1基因编码的神经肽Kisspeptin通过Kissspeptin受体(Kiss1r)直接向GnRH神经元发出信号来激活生殖。Kiss1/Kisspeptin细胞存在于几个脑区，主要是下丘脑前腹侧脑室周围核(灵长类和绵羊的视前区)、下丘脑弓状核和杏仁核，但对Kissspeptin在杏仁核中的调节和功能关注很少。杏仁内侧核(Mea)是一个雌激素敏感区域，参与调节生殖内分泌和行为，但mea影响生殖的机制(S)以及这些机制是否在男性和女性之间相似，仍不清楚。此外，MEA对生殖生理和行为方面的嗅觉信息的辨别和调节也很重要，MEA神经元对异性气味进行区分和选择性反应。然而，对所涉及的特定MEA细胞类型的识别以及发生这种情况的机制仍然知之甚少。鉴于Kispeptin治疗改变了生殖生理，并且Kispeptin信号是异性气味偏好所必需的，因此MeA中的kispeptin神经元可能在这些特定的生殖事件中发挥重要作用。这个项目的总体目标是研究Kiss1神经元在MEA中的调节和生殖功能，目前对此几乎一无所知。目的1研究Mea Kiss1神经元的神经解剖学投射，以确定mea Kiss1神经元是否直接投射到GnRH神经元，从而有可能直接影响生殖，以及Mea Kiss1传出投射在男性和女性中是否相似。目的2直接检测MEA中Kiss1神经元生殖功能的可能性，以及MEA中Kiss1神经元对异性气味偏好的影响。此外，《目标2》还探讨了男性和女性大脑中脑区Kiss1神经元的潜在功能是否相似。目的3将确定mea Kiss1神经元活跃表达哪些基因，这种分子表型是否依赖于E2，以及mea Kiss1神经元表达的基因是否在雄性和雌性之间存在差异，所有这些都将为了解这些特定的Kiss1神经元的调节和潜在功能提供新的和基本的见解。除了调节生殖外，mea还调节应激、焦虑和社会行为等多种行为，这项研究不仅将确定mea Kiss1神经元在调节生殖中的作用，还将为进一步探索mea kiss1神经元潜在的非生殖功能提供基础。总之，这项工作可能会为不孕症、无排卵、闭经和特发性低促性腺激素减退症的治疗提供重要的信息，并提高我们对与杏仁核功能异常相关的疾病的生殖生理调节的理解。