The role of the amygdala in modulating reproduction

杏仁核在调节生殖中的作用

• 批准号: 9371493
• 负责人: Shannon Brooke Zoe Stephens
• 金额: $ 9.52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9371493
• 关键词: Ablation; Adolescent; Adult; Age; Amenorrhea; Amygdaloid structure; Anovulation; Anterior; Ants; Area; Autistic Disorder; Behavior; Behavioral; Brain; Brain region; Cell Nucleus; Delayed Puberty; Disease; Electric Stimulation; Emotions; Feedback; Female; Fertility; GNRH1 gene; Genetic; Glutamates; Hypothalamic structure; Impairment; Infertility; KISS1 gene; Kallmann Syndrome; Lesion; Medial; Mediating; Molecular; Molecular Profiling; Neurons; Neuropeptides; Neurosecretory Systems; Neurotransmitters; Ovarian Cycles; Physiological; Pituitary Gland; Puberty; Regulation; Reproduction; Reproductive Endocrinology; Reproductive Physiology; Research; Rodent; Role; Schizophrenia; Sex Characteristics; Signal Transduction; Techniques; Temporal Lobe; Work; cell type; gamma-Aminobutyric Acid; hypothalamic pituitary gonadal axis; infertility treatment; insight; male; molecular phenotype; neural tract; novel; prepuberty; receptor; relating to nervous system; reproductive axis; reproductive function; social

PROJECT SUMMARY Reproduction and puberty onset are regulated by the hypothalamic-pituitary-gonadal (HPG) axis, but despite much research, the mechanisms that can modulate the HPG axis, as well as disrupt the HPG axis, are not fully understood. To date, most research has focused primarily on the mechanisms within the hypothalamus that regulate the HPG axis, with little focus on how extra-hypothalamic brain regions may modulate reproduction. The amygdala is located in the medial temporal lobe and the medial nucleus of the amygdala (MeA), has numerous behavioral and physiological functions, including effects on puberty and reproductive physiology. However, the mechanisms by which the MeA modulates puberty onset and reproduction are completely unknown. The neuropeptide kisspeptin regulates reproduction by activating GnRH neurons. Kisspeptin neurons are detected in several discrete brain areas, primarily the hypothalamus and MeA, but the regulation and function of kisspeptin in the MeA is poorly understood. Thus, kisspeptin in the MeA may be one mechanism by which the amygdala modulates reproduction. Aim 1 will examine the role of kisspeptin in the MeA’s modulation of reproduction by: 1) examining possible reproductive functions of MeA Kiss1 neurons in adulthood by selectively destroying or activating MeA Kiss1 neurons; 2) identify the molecular phenotype of MeA Kiss1 neurons to understand what other signaling factors, if any, are made in kisspeptin neurons, as well as identify receptors in MeA Kiss1 neurons that may give insight into how these neurons are regulated; 3) examine how the MeA region may be “talking” to the HPG axis by determine if there are neural projections from the MeA to hypothalamic Kiss1 and GnRH neurons. Like kisspeptin, glutamate and GABA neurons are also highly expressed in the MeA and have been shown to regulate puberty, implicating glutamate and GABA as additional mechanisms by which the MeA may modulate puberty. Aim 2 focuses on the role of 1) GABA in the anterior MeA and 2) glutamate and kisspeptin in the posterior MeA, in regulating puberty onset. It is also currently unknown whether the MeA modulates adult reproduction and puberty onset in males as it does in females, and this proposal will examine both males and females to identify any sex differences, especially since puberty onset is sexually dimorphic (females earlier than males). In summary, this proposal seeks to identify the molecular mechanism(s) and specific cell types involved in the MeA’s modulation of reproductive endocrinology. This work may provide important novel information relevant to treatments in infertility, anovulation, idiopathic hypogonadotropic hypogonadism, and amenorrhea, as well as understanding reproductive physiology in disorders associated with aberrant amygdala function, such as autism and schizophrenia. The MeA is also known to modulate numerous emotions and physiological states and therefore, this project may provide new insight regarding how social information modulates reproductive physiology.

项目概要 生殖和青春期的开始是由下丘脑-垂体-性腺（HPG）轴调节的，但尽管如此 大量研究表明，调节 HPG 轴以及破坏 HPG 轴的机制尚未完全阐明。 明白了。迄今为止，大多数研究主要集中在下丘脑内的机制 调节 HPG 轴，很少关注下丘脑外大脑区域如何调节生殖。 杏仁核位于内侧颞叶和杏仁核内侧核（MeA），具有 许多行为和生理功能，包括对青春期和生殖生理的影响。 然而，MeA 调节青春期开始和生殖的机制是完全不明确的。 未知。神经肽 Kisspeptin 通过激活 GnRH 神经元来调节生殖。吻肽 在几个离散的大脑区域中检测到神经元，主要是下丘脑和 MeA，但调节 对 Kisspeptin 在 MeA 中的功能知之甚少。因此，MeA 中的 Kisspeptin 可能是其中之一 杏仁核调节生殖的机制。目标 1 将研究 Kisspeptin 在 MeA 通过以下方式调节生殖：1）检查 MeA Kiss1 神经元的可能生殖功能 通过选择性破坏或激活 MeA Kiss1 神经元进入成年期； 2) 鉴定分子表型 MeA Kiss1 神经元，了解 Kisspeptin 神经元中还产生哪些其他信号因子（如果有） 识别 MeA Kiss1 神经元中的受体，可以深入了解这些神经元的调节方式； 3） 通过确定是否存在神经投射来检查 MeA 区域如何与 HPG 轴“对话” 从 MeA 到下丘脑 Kiss1 和 GnRH 神经元。与 Kisspeptin 一样，谷氨酸和 GABA 神经元也 在 MeA 中也​​高度表达，并已被证明可以调节青春期，涉及谷氨酸和 GABA 作为 MeA 调节青春期的附加机制。目标 2 重点关注 1) GABA 在 前 MeA 和 2) 后 MeA 中的谷氨酸和 Kisspeptin，调节青春期的开始。这也是 目前尚不清楚 MeA 是否能像在男性中那样调节成年生殖和青春期的开始。 女性，该提案将检查男性和女性，以确定任何性别差异，特别是 因为青春期的开始具有性别二态性（女性早于男性）。总而言之，该提案旨在 确定参与 MeA 生殖调节的分子机制和特定细胞类型 内分泌学。这项工作可能提供与不孕症治疗相关的重要新颖信息， 无排卵、特发性低促性腺激素性性腺功能减退症和闭经以及理解 与杏仁核功能异常相关的生殖生理学，例如自闭症和 精神分裂症。 MeA 还可以调节多种情绪和生理状态，因此， 该项目可能会提供有关社会信息如何调节生殖生理学的新见解。