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The role of the amygdala in modulating reproduction

杏仁核在调节生殖中的作用

基本信息

批准号：
10219313
负责人：
Shannon Brooke Zoe Stephens
金额：
$ 23.81万
依托单位：
ALBANY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10219313
关键词：
Ablation Adolescent Adult Age Amenorrhea Amygdaloid structure Anovulation Anterior Ants Area Behavior Behavioral Brain Brain region Cell Nucleus Delayed Puberty Disease Electric Stimulation Emotions Feedback Female Fertility GNRH1 gene Genetic Glutamates Hypothalamic structure Idiopathic Hypogonadotropic Hypogonadism Impairment Infertility KISS1 gene 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 Differences Signal Transduction Techniques Temporal Lobe Work autism spectrum disorder 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 sexual dimorphism social

项目摘要

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.

项目摘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，尽管有很多研究，但能够调节HPG轴以及破坏HPG轴的机制并不完全明白迄今为止，大多数研究主要集中在下丘脑内的机制，调节HPG轴，很少关注下丘脑外脑区如何调节生殖。杏仁核位于内侧颞叶和杏仁核内侧核（MeA），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完全不清楚。未知神经肽kisspeptin通过激活GnRH神经元调节生殖。kisspeptin 神经元在几个离散的大脑区域中被检测到，主要是下丘脑和MeA，但调节 Kisspeptin在MeA中的功能尚不清楚。因此，MeA中的kisspeptin可能是一个杏仁核调节生殖的机制。目的1将研究kisspeptin在 MeA通过以下方式调节生殖：1）检查MeA Kiss 1神经元的可能生殖功能，成年期通过选择性破坏或激活MeA Kiss 1神经元; 2）鉴定 MeA Kiss1神经元，以了解kisspeptin神经元中还产生了哪些其他信号因子（如果有的话）。作为识别MeA Kiss 1神经元中的受体，可以深入了解这些神经元是如何调节的; 3）通过确定是否存在神经投射来检查MeA区域如何与HPG轴"交谈" 从MeA到下丘脑Kiss 1和GnRH神经元。和kisspeptin一样，谷氨酸和GABA神经元也是也在MeA中高度表达，并已被证明可调节青春期，涉及谷氨酸和GABA 作为MeA调节青春期的额外机制。目标2重点关注1）GABA在 2）后MeA中的谷氨酸和kisspeptin，在调节青春期启动中的作用。也是目前尚不清楚MeA是否能像在哺乳动物中一样调节雄性的成年生殖和青春期的开始。女性，这项建议将检查男性和女性，以确定任何性别差异，特别是因为青春期的开始是两性的（女性比男性早）。总而言之，这项建议旨在确定参与MeA调节生殖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信息，不排卵、特发性低促性腺激素性性腺功能减退和闭经，以及了解与异常杏仁核功能相关的疾病的生殖生理学，如自闭症和精神分裂症MeA还已知调节许多情绪和生理状态，因此，这个项目可能提供关于社会信息如何调节生殖生理学的新见解。