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Identification and Validation of Human Hypothalamic Nuclei in-vivo and ex-vivo Us

体内和离体人类下丘脑核团的鉴定和验证

基本信息

批准号：
7891395
负责人：
NIKOLAOS MAKRIS
金额：
$ 22.13万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-10 至 2012-03-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7891395
关键词：
Adrenal Glands Adult Anatomy Autopsy Brain Brain imaging Cardiovascular system Cell Nucleus Clinical Medicine Corticotropin-Releasing Hormone Data Detection Disease Endocrine Estrogen Receptor 1 Estrogen Receptors Female Functional Magnetic Resonance Imaging Functional disorder Future Goals Gonadal Hormones Histological Techniques Hormonal Human Hypothalamic structure Image Life Magnetic Resonance Imaging Major Depressive Disorder Manuals Maps Medical Menstrual cycle Mental Depression Mental disorders Methodology Methods Neuroanatomy Neurologic Neurons Noise Organ Patients Pituitary Gland Preparation Protocols documentation Public Health Regulation Reproductive system Resolution Role Sampling Scanning Schizophrenia Sex Characteristics Signal Transduction Sleep Disorders Specimen Staining method Stains Structure System Tissues Validation Weight Woman Women&apos s Health Work human subject human tissue hypothalamic-pituitary-adrenal axis imaging modality in vivo innovation male men neuroimaging paraventricular nucleus public health relevance supraoptic nucleus

项目摘要

DESCRIPTION (provided by applicant): There is increasing evidence regarding the importance of the hypothalamus for understanding women's health and sex differences in relation to neurological, psychiatric, endocrine and sleep disorders. In fact, hypothalamic nuclei, key regulators of autonomic and endocrine functions, are some of the most highly sexually dimorphic nuclei in the brain and implicated in psychiatric and medical disorders with known sex differences. We would argue that an understanding of hormonal effects on the brain and the regulation of other organs and/or systems, such as the cardiovascular and reproductive systems, are critical as downstream effects of hypothalamic activity. Thus an understanding of the neuroanatomy of hypothalamic nuclei and how they are differentially disrupted in men and women in specific disorders will contribute to elucidating sex differences in clinical medicine. However, the identification of hypothalamic nuclei in-vivo in humans has not been realized. This is important since studies have shown the association of the hypothalamus, endocrine dysfunction and sex differences in psychiatric disorders. In fact, the paraventricular hypothalamic nucleus (PVN) is enlarged in patients with major depressive disorder (MDD), in PVN neurons that are dense in corticotropin releasing hormone (CRH) and estrogen receptor (ER)1. In our recent work in schizophrenia (SCZ) we identified structural abnormalities using MRI in the hypothalamus particularly in the PVN in women. Furthermore, in healthy women we showed, using functional MRI, regulation of brain activity in hypothalamic nuclei such as the PVN, dependent on gonadal hormone changes over the menstrual cycle. The principal focus of this study is to use a new in-vivo methodology for the assessment of the hypothalamus comparing neuroimaging data using 7 Tesla magnetic resonance imaging (MRI) and human postmortem validation. The proposed study aims to identify the PVN in-vivo and ex-vivo in the human hypothalamus using high field MRI, to investigate the relationship of the MRI methodology and the histological technique, and to establish the correlates of the histological structures with the MRI representations. In addition to the PVN, which is critical for its role within the hypothalamic-pituitary-adrenal (HPA) axis and its dysfunction in MDD and SCZ, we will identify the supraoptic nucleus (SON), which will be used as a control region. High-resolution 7 Tesla MRI will be carried out in thirty healthy subjects, and four ex-vivo human hypothalamic samples. Our overarching goal is an innovative methodological one: to identify the PVN of the human hypothalamus in healthy adult women and men in-vivo. We expect this method, once defined, to be applied clinically in subjects with MDD and SCZ. PUBLIC HEALTH RELEVANCE: Hypothalamic nuclei will be identified in living humans using high field magnetic resonance imaging (MRI) (i.e., a 7 Tesla scanner) and in ex-vivo human hypothalamic tissue. The MRI results will be compared with postmortem human tissue to assure methodological validation. These hypothalamic nuclei are key regulators of autonomic and endocrine functions implicated in numerous psychiatric and medical disorders with known sex differences such as depression and schizophrenia. Understanding sex differences and the hypothalamic involvement in relation to neurological, psychiatric, cardiovascular, endocrine and sleep disorders is very relevant for public health in general and women's health in particular.

描述（由申请人提供）：有越来越多的证据表明，下丘脑对于了解女性健康和神经、精神、内分泌和睡眠障碍方面的性别差异具有重要意义。事实上，下丘脑核团，自主神经和内分泌功能的关键调节器，是大脑中最高度性别二态性的核团之一，并与已知性别差异的精神和医学疾病有关。我们认为，了解激素对大脑的影响以及对其他器官和/或系统（如心血管和生殖系统）的调节，是下丘脑活动的下游效应。因此，了解下丘脑核团的神经解剖学，以及它们在特定疾病中如何在男性和女性中被不同地破坏，将有助于阐明临床医学中的性别差异。然而，在人体内的下丘脑核的识别尚未实现。这一点很重要，因为研究表明下丘脑、内分泌功能障碍和精神疾病的性别差异之间存在关联。事实上，重度抑郁症（MDD）患者的下丘脑室旁核（PVN）扩大，在促肾上腺皮质激素释放激素（CRH）和雌激素受体（ER）1密集的PVN神经元中。在我们最近对精神分裂症（SCZ）的研究中，我们使用MRI确定了女性下丘脑特别是PVN的结构异常。此外，在健康女性中，我们使用功能性MRI显示，下丘脑核团（如PVN）的大脑活动调节依赖于月经周期中性腺激素的变化。本研究的主要重点是使用一种新的体内方法来评估下丘脑比较神经影像学数据，使用7特斯拉磁共振成像（MRI）和人类尸检验证。本研究的目的是利用高场MRI对人下丘脑室旁核进行活体和离体定位，探讨MRI方法学和组织学技术之间的关系，并建立组织学结构与MRI表现的相关性。除了PVN（其在下丘脑-垂体-肾上腺（HPA）轴中的作用及其在MDD和SCZ中的功能障碍至关重要）之外，我们还将确定视上核（SON），该视上核将用作对照区域。将对30名健康受试者和4份离体人下丘脑样本进行高分辨率7特斯拉MRI。我们的总体目标是一个创新的方法之一：在体内识别健康成年女性和男性的人类下丘脑PVN。我们希望这种方法，一旦定义，将在临床上应用于MDD和SCZ受试者。公共卫生相关性：将使用高场磁共振成像（MRI）（即，7特斯拉扫描仪）和离体人下丘脑组织。将MRI结果与死后人体组织进行比较，以确保方法学验证。这些下丘脑核团是自主神经和内分泌功能的关键调节器，涉及许多具有已知性别差异的精神和医学疾病，如抑郁症和精神分裂症。了解性别差异和下丘脑与神经、精神、心血管、内分泌和睡眠障碍的关系，对一般公共卫生，特别是妇女的健康非常重要。